Colistin is used in treatment against gram-negative bacteria. It causes toxic effects due to oxidative stress in a dose-dependent manner. Naringin is a flavonoid with strong antioxidant properties found naturally in many plants, especially citrus fruits. This study aimed to determine the protective effects of NRG in CLS-induced sciatic nerve injury. Thirty-five male Spraque rats were randomly divided into five groups: control, NRG, CLS, CLS+NRG50, and CLS+NRG100. CLS was administered orally at a 15mg/kg for seven days. NRG was administered orally at 50 or 100 mg/kg for seven days. CLS caused toxic damage in sciatic nerve tissue by increasing MDA and decreasing antioxidant capacity (SOD, CAT, GPx, and GSH); increasing NF-κB, TNF-α, nNOS release; increasing apoptotic factor (Caspase-3); decreasing HO-1 and nCAM; and inducing 8-OHdG, MAPK and GFAP. NRG, on the other hand, reversed all these changes in sciatic nerve tissue and reduced CLS-induced oxidative stress damage, inflammatory damage and apoptotic damage. These effects were more effective at the 100mg/kg dose of NRG than at the 50mg/kg dose. In sciatic nerve tissue, CLS-induced sciatic nerve toxicity with increased oxidative stress, inflammation, and apoptotic damage. NRG showed a protective effect against CLS-induced sciatic nerve toxicity.

The impact of metals bioaccumulation on marine organisms is under investigation. This study was designed to determine the association of oxidative stress in mussels Mytilus galloprovincialis induced by seawater enriched with trace metals with protein synthesis. Mussels were exposed to 40 μg/L Cu, 30 μg/L Hg, or 100 μg/L Cd for 5 and 15 days, and the pollution effect was evaluated by measuring established oxidative biomarkers. The results showed damage on the protein synthesis machine integrity and specifically, on translation factors and ribosomal proteins expression and modifications. Exposure of mussels to all metals caused oxidative damage that was milder in the cases of Cu and Hg, and more pronounced for Cd. However, after prolonged exposure of mussels to Cd (15 days), the effects receded. These changes that perturb protein biosynthesis can serve as a great tool for elucidating the mechanisms of toxicity and could be integrated in biomonitoring programs.

Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress and apoptosis. While the protective mechanism of aspalathin remains unknown, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has emerged as a key factor for intracellular responses against oxidative stress. Therefore, we hypothesized that aspalathin protects the myocardium against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice. Using an oxidative stress RT2 Profiler PCR array, ASP at a dose of 1 µM was demonstrated to protect H9c2 cardiomyocytes against HG-induced oxidative stress, but silencing of Nrf2 abolished this protective response of ASP and exacerbated cardiomyocyte apoptosis. Db/db mice and their non-diabetic (db/+) littermate controls were subsequently treated daily for 6 weeks with either a low (13 mg/kg) or high (130 mg/kg) ASP dose. Compared to nondiabetic mice the db/db mice presented increased cardiac remodeling and enlarged left ventricular wall that occurred concomitant to enhanced oxidative stress. Daily treatment of mice with ASP at a dose of 130 mg/kg for 6 weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes. These results indicate that ASP maintains cellular homeostasis and protects the myocardium against hyperglycemia-induced stress through activation of Nrf2 and its downstream target genes.

(1) Background: The severity of malaria is associated with low bioavailability of antioxidants and high concentration of free radicals that induce oxidative damage in cerebral and pulmonary microcirculation. This can be prevented by the action of consumable antioxidants present in foods. Therefore, we investigated the protective role of lycopene (LYC) on the oxidative changes induced by Plasmodium berghei (Pb); (2) Methods: Mice were infected by intraperitoneal injection of 106 parasitized red blood cells and treated via gavage with LYC (3.11 mg/kg bw/day) or NAC (62 mg/kg bw/day). They were then evaluated for 1, 4, 8 or 12 days after infection. Levels of thiobarbituric acid reactive substances (TBARS), antioxidant capacity by inhibition of ABTS radicals (AC-ABTS) and DPPH (AC-DPPH), uric acid (UA), and nitric oxide (NO) were measured in brain and lung tissues; (3) Results: The infection caused oxidative stress confirmed by increased levels of TBARS, AC-ABTS, AC-DPPH, UA, and NO in the tissues leading to the death of the animals. LYC prevented the increase in TBARS, AU, and NO levels compared to Pb (p< 0.0001) and NAC+Pb groups (p<0.0001), reaching values similar to those of Sham animals; (4) Conclusions: These results are striking evidence of the beneficial effect of lycopene supplementation on oxidative stress in experimental malaria in vivo and emphasize the importance of antioxidant supplementation in the treatment of the disease.

In various models of chronic kidney disease, the amount and localization of Cx43 in the nephron is known to increase, but the intracellular pathways that regulate these changes have not been identified. Therefore, we proposed that: "In the model of renal damage induced by infusion of angiotensin II (AngII), a RhoA/ROCK-dependent pathway, is activated and regulates the abundance of renal Cx43”. In rats, we evaluated: 1) the time-point where the renal damage induced by AngII is no longer reversible; and 2) the involvement of a RhoA/ROCK-dependent pathway and its relationship with the amount of Cx43 in this irreversible stage. Systolic blood pressure (SBP) and renal function (urinary protein/urinary creatinine: Uprot/UCrea) were evaluated as systemic and organ outcomes, respectively. In kidney tissue, we also evaluated: 1) oxidative stress (amount of thiobarbituric acid reactive species), 2) inflammation (immunoperoxidase detection of the inflammatory markers ED-1 and IL-1β), 3) fibrosis (immune detection of type III collagen; Col III) and 4) activity of RhoA/ROCK (amount of phosphorylated MYPT1; p-MYPT1). The ratio Uprot/UCrea, SBP, oxidative stress, inflammation, amount of Cx43 and p-MYPT1 remained high 2 weeks after suspending AngII treatment in rats treated for 4 weeks with AngII. These responses were not observed in rats treated with AngII for less than 4 weeks, in which all measurements returned spontaneously close to the control values after suspending AngII treatment. Rats treated with AngII for 6 weeks and co-treated for the last 4 weeks with Fasudil, an inhibitor of ROCK, showed high SBP but did not present renal damage or increased amount of renal Cx43. Therefore, renal damage induced by AngII correlates with the activation of RhoA/ROCK and the increase in Cx43 amounts and can be prevented by inhibitors of this pathway.

The purpose of the present study was to examine if 14 days of supplementation with a pine bark extract leading up to and following an exercise test would increase performance and reduce biomarkers associated with muscle damage, inflammation and oxidative stress. The study used a double-blind, placebo controlled, cross-over design. Participants ingested either 800mg pine bark extract or placebo for 14 days prior to the first exercise trial and for 2 days post-exercise. On the exercise day, participants submitted a pre-exercise blood sample, then completed a VO₂ peak test until volitional failure. A post-blood sample was collected 1 hour after completion of exercise. Participants returned at 24 & 48 hours after the exercise testing for measures of muscle pain in the lower body using an algometer. Participants then had a 7-day washout period before beginning to crossing over to the alternate treatment. Analysis via ordinal regression demonstrated a significant difference in oxidative stress in the pine bark extract group compared to placebo (ChiSq = 2.63; p = 0.05). The pine bark extract was effective at affording protection from oxidative stress post exercise. Further work should be undertaken to evaluate the findings with other exercise modes or in participants with known metabolic syndrome.

(1) Background: Ultra-endurance exercise involves a high physical impact, resulting in muscle damage, inflammatory response and production of free radicals that alter the body's oxidative state. Supplementation with antioxidants, such as beetroot, may improve recovery in ultra-endurance runners. The aim of this study was to determine whether there is a correlation between the beetroot intake and the recovery of serum oxidative status, inflammatory response and muscle damage parameters after an ultra-endurance race. (2) Methods: An observational and longitudinal study was conducted by means of surveys and blood samples collected from 32 runners during the IX Penyagolosa Trails CSP® race and the two following days. The variables C-reactive protein (CRP), lactate dehydrogenase (LDH), creatine kinase (CK), the activity of the antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GR), as well as the oxidative damage markers malondialdehyde (MDA), carbonyl groups (CG) and loss of muscle strength using the Squat Jump test (SJ) were analyzed to discriminate whether beetroot consumption can modulate the recovery of ultra-trail runners. (3) Results: Significant differences were observed between runners who ingested beetroot and those who did not, in terms of oxidative status, specifically in serum GPx activity at 24 and 48 hours, muscle damage variables CK and LDH and in SJ test at the finish line. Therefore, the intake of supplements containing beetroot positively influences the recovery of serum oxidative status and muscle damage after ultra-endurance running.

Furazolidone (FZD) is a synthetic nitrofuran with the antiprotozoal and antibacterial activity. The proper mechanism of FZD induced toxicity is still unclear. This study aimed to investigate the protective effect of curcumin on FZD induced oxidative stress, DNA injury and apoptosis in human hepatocyte L02 cells. The results showed that curcumin treatment significantly ameliorated FZD induced cytotoxicity, characterized by decreasing the production of reactive oxygen species (ROS) and malondialdehyde, as well as increasing superoxide dismutase, catalase activities and glutathione contents. Moreover, curcumin pretreatment significantly inhibited FZD induced the loss of mitochondrial membrane potential, the activation caspase-9 and -3 and apoptosis. Comet assay showed that curcumin attenuated FZD induced DNA injury in a dose-dependent manner. Correspondingly, curcumin markedly reversed the up-regulation of p53, Bax, caspase-9 and -3 mRNA expressions and the down-regulation of Bcl-2 mRNA (all p<0.05 or 0.01). These results reveal that curcumin protects against FZD induced oxidative stress, DNA injury and cell apoptosis via inhibiting oxidative stress and mitochondrial pathway, which may be attributed to ROS scavenging and anti-oxidative ability of curcumin. Importantly, our study highlights that curcumin may be a potential way to prevent FZD-mediated oxidative DNA injury and apoptosis in human or animals.

Boldine, a major aporphine alkaloid found in Chilean boldo tree, is a potent antioxidant. Oxidative stress plays a detrimental role in the pathogenesis of kidney damage in Renovascular hypertension (RVH). The activation of the Renin-Angiotensin System (RAS) is crucial in the development and progression of hypertensive renal damage and TGF-β is closely associated with the activation of RAS. In the present study, we assessed the effect of boldine on the progression of kidney disease using the 2K1C hypertension model and identifying mediators in the RAS such as TGF-β, that could be modulated by this alkaloid. Toward this hypothesis, rats (n=5/group) were treated with boldine (50mg/kg/day, gavage) for 6 weeks after 2K1C surgery (pressure≥180mmHg). Kidney function was evaluated by measuring of proteinuria/creatininuria ratio (U prot/U Crea), oxidative stress (OS) by measuring thiobarbituric acid reactive substances (TBARS). The evolution of systolic blood pressure (SBP) was followed weekly. α-SMA and Col III were used as markers of kidney damage; ED-1 and Osteopontin (OPN) as markers of inflammation. We also explored the effect in RAS mediators, such as ACE-1 and TGF-β. Boldine treatment reduced UProt/UCrea ratio, plasma TBARS and slightly reduced SBP in 2K1C hypertensive rats, producing no effect in control animals. In 2K1C rats treated with boldine the levels of α-SMA, Col III, ED-1 and OPN were lower when compared to 2K1C rats. Boldine prevented the increase in ACE-1 and TGF-β in 2K1C rats, suggesting that boldine reduces kidney damage. These results suggest that boldine could potentially be used as a nutraceutic.

This study investigated the neuroprotective effects of methyl 3,4-dihydroxybenzoate (MDHB) against t-butylhydroperoxide(TBHP) induced oxidative damage in SH-SY5Y (human neuroblastoma cells) and the underlying mechanisms. SH-SY5Y were cultured in DMEM+10% FBS for 24 hours and pretreated with different concentrations of MDHB or N-acetyl-L-cysteine (NAC) for 4 hours prior to the addition of 40 μM TBHP for 24 hours. Cell viability was analyzed using the methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) assays. An annexin V-FITC assay was used to detect cell apoptosis rate. The 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay was used to determine intracellular ROS levels. The activities of antioxidative enzymes (GSH-Px and SOD) were measured using commercially available kits. The oxidative DNA damage marker 8-OHdG was detected using ELISA. Western blotting was used to determine the expression of Bcl-2, Bax, caspase 3, p-Akt and Akt proteins in treated SH-SY5Y cells. Our results showed that MDHB is an effective neuroprotective compound that can mitigate oxidative stress and inhibit apoptosis in SH-SY5Y cells

Age-related macular degeneration (AMD) is a complex, progressive degenerative retinal disease. Retinal pigment epithelial (RPE) cells play an important role in the immune defense of the eye, and their dysfunction leads to the progressive irreversible degeneration of photoreceptors. Genetic factors, chronic inflammation, and oxidative stress have been implicated in AMD pathogenesis. Oxidative stress causes RPE injury, resulting in a chronic inflammatory response and cell death. The Y402H polymorphism in the complement factor H (CFH) protein is an important risk factor for AMD. However, the functional significance of CFH Y402H polymorphism remains unclear. In the present study, we investigated the role of CFH in the proinflammatory response using an in vitro model of oxidative stress in the RPE with the at-risk CFH Y402H variant. : ARPE-19 cells with the at-risk CFH Y402H variant were highly susceptible to damage caused by oxidative stress, with increased levels of inflammatory mediators and pro-apoptotic factors that lead to cell death. Pretreatment of ARPE-19 cell cultures with exogenous CFH prior to the induction of oxidative stress prevented damage and cell death. This protective affect may be related to the negative regulation of pro-inflammatory cytokines. CFH contributes to cell homeostasis and is required to modulate the pro-inflammatory cytokine response under oxidative stress in the ARPE-19 cells with the at-risk CFH Y402H variant.

The mechanization of agricultural activities has led to indiscriminate deposition of toxic xenobiotics, including organophosphates in the biomes, and this has led to intoxication characterized with deleterious oxidative and neuronal changes. This study investigated the consequences of oxidative and neurogenic disruptions that follow exposure to two organophosphates, chlorpyrifos (CPF) and dichlorvos (DDVP) on neuro-cognitive performance and anxiety-like behaviors in rats Thirty-two adult male Wistar rats (150 – 170g) were randomly divided into 4 groups, orally exposed to normal saline (NS), DDVP (8.8mg/kg), CPF (14.9mg/kg) and DDVP+CPF for 14 consecutive days. On day 10 of exposures, anxiety-like behaviors and amygdala dependent fear learning were assessed using Open Field and Elevated Plus Maze paradigms respectively, while spatial working memory was assessed on day 14 in the Morris water maze paradigm, following 3 training trials each on days 11, 12 and 13. On day 15, the rats were euthanized, and their brains excised, hippocampus and amygdala removed, 5 of which were homogenized and centrifuged to analyze nitric oxide (NO) metabolites, total reactive oxygen species (ROS), and acetylcholinesterase (AChE) activity, and the other three processed for histology (cresyl violet stain) and proliferative marker (Ki67 immunohistochemistry). Marked (p≤0.05) loss in body weight, AChE depletion, and overproduction of both NO and ROS were observed after repeated exposure to individual and combined doses of CPF and DDVP. Insults from DDVP exposure appeared more severe owing to the observed greater losses in the body weights of exposed rats. There was also a significant (p≤0.05) effect on the cognitive behaviors recorded from the exposed rats, and these deficits were related to the oxidative damage and neurogenic cell loss in the hippocampus and the amygdala of the exposed rats. Taken together, these results provided an insight that oxidative and neurogenic damages are central to the severity of neuro-cognitive dysfunction and increased anxiety-like behaviors that follow organophosphate poisoning.

The functions of annexin A1 (ANXA1) that is expressed on membranes and in cytoplasmic granules have been fully described. Nonetheless, the role of this protein in protecting against DNA damage in the nucleus is still emerging and requires further investigation. Here, we investigated the involvement of ANXA1 in DNA damage response in placental cells. Placenta was collected from ANXA1 knockout mice (AnxA1-/-) and pregnant women with gestational diabetes mellitus (GDM). The placental morphology and ANXA1 expression, which are related to the modulation of cellular response markers in the presence of DNA damage, were analyzed. Total area of AnxA1-/- placenta was smaller because of reduced labyrinth zone, enhanced DNA damage, and impaired base excision repair (BER) enzymes, which resulted in the induction of apoptosis in the labyrinthine and junctional layers. The placentas from pregnant women with GDM showed reduced expression of AnxA1 in the villous compartment, increased DNA damage, apoptosis, and reduction of enzymes involved in the BER pathway. Our translational data provide valuable insights into the possible involvement of ANXA1 in the response of placental cells to oxidative DNA damage and represent advancement in investigations on the mechanisms involved in placental biology.

Incident rates of neurodegenerative diseases have steadily increased globally, but there is no therapeutic access available. We newly prescribed medicinal herbal remedy including five different herbal plants called, Chen-Ma-Dan-Sam-Ga-Mi-Bang (CMST), purposed to prove for pharmacological properties and corresponded actions on hippocampus neuronal cell injury by hypoxia-induced mice model. Mice were adapted to normoxia or hypoxia with or without CMST for 5 days. We gathered pharmacological effects of CMST on cell injury by enhancement of dihydroethidium and 4-hydroxynonenal signals which were correlated with abnormal redox status in the protein or gene expression levels (abnormal elevations of nitric oxide, reactive oxygen species, lipid peroxidation and deteriorations of total glutathione, total antioxidant capacity, and activities of superoxide dismutase and catalase) due to hypoxia. CMST also notably exerted to attenuates molecules for neuronal cell injury markers such as p-tau, cleaved caspase-3 due to DNA oxidations (53bp1and phosphor-histone H2AX), inflammatory cytokines, and hemeoxigenase-1. We further figured out the underlying actions of CMST by in vitro experiment through inactivation of microglial cell which can mediate neuronal cell injury. Collectively, CMST prevented from hippocampal neuronal cells via inactivation of microglial cell with normalization of redox status on hypoxia-induced hippocampus neuronal cell injury.

Deficit schizophrenia is characterized by leaky tight and adherens junctions and bacterial translocation. Here we examine whether (deficit) schizophrenia is accompanied by leaky paracellular, transcellular and vascular barriers in the gut and blood brain barriers. We measured IgA responses to occludin, claudin-5, E-cadherin and β-catenin (paracellular pathway, PARA), talin, actin, vinculin and epithelial intermediate filament (transcellular pathway, TRANS) and plasmalemma vesicle-associated protein (PLVAP, vascular pathway) in 78 schizophrenia patients and 40 controls. IgA responses to claudin-5, E-cadherin and β-catenin, the sum of the four PARA proteins and the ratio PARA/TRANS were significantly higher in deficit schizophrenia than in non-deficit schizophrenia and controls. A large part of the variance in PHEMN (psychosis, hostility, excitation, mannerism and negative) symptoms, psychomotor retardation, formal thought disorders, verbal fluency, word list memory, word list recall and executive functions was explained by the PARA/TRANS ratio coupled with plasma IgA responses to Gram-negative bacteria, IgM to malondialdehyde, CCL-11 (eotaxin), IgA levels of the ratio of noxious to more protective tryptophan catabolites (NOX/PRO TRYCATs) and a plasma immune activation index. Moreover, IgA levels to Gram-negative bacteria were significantly associated with IgA to E-cadherin, β-catenin and PLVAP, while IgA levels to claudin-5 were significantly predicted by IgA to E-cadherin, NOX/PRO TRYCAT ratio, Gram-negative bacteria and CCL11. The phenomenology of the deficit syndrome is to a large extent explained by the cumulative effects of lowered natural IgM, breakdown of the paracellular and vascular pathways, increased bacterial translocation, peripheral immune-inflammatory responses and indices of BBB breakdown.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to re-duce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and re-duction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Natural antioxidants have also recently been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measure-ments at baseline and after completion of the three weeks PR. We found that high vegetable in-take in normal diet, without any specific intervention, can increase the probability to success-fully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of Non-Responders, p=0.033). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an im-provement in the patient's inflammatory state.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to re-duce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and re-duction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Natural antioxidants have also recently been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measure-ments at baseline and after completion of the three weeks PR. We found that high vegetable in-take in normal diet, without any specific intervention, can increase the probability to success-fully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of Non-Responders, p=0.033). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an im-provement in the patient's inflammatory state.

The Ramazzottius varieornatus tardigrade is an extremotolerant terrestrial invertebrate belonging to the phylum of Tardigrada. At a length of 0.1-1.0 mm, tardigrades are small animals with an exceptional tolerance to extreme conditions such as high pressure, chemicals and irradia-tion. These properties have been attributed to the recently-discovered Dsup protein. Dsup is a nucleosome-binding protein that prevents DNA damage against X-ray and oxidative stress without impairing cell life, also in Dsup-transfected animal and plant cells. However, the precise “protective” role of this protein is still under study. We performed experiments on human cells and shows that, as compared to control cells, Dsup+ cells are more resistant to UV-C exposure and H2O2. Real-time PCR identified different expression patterns of endogenous genes involved in apoptosis, cell survival and DNA damage repair in Dsup+ cells in response to H2O2 and UV-C. While H2O2 treatment in Dsup+ cells only marginally involved the activation of pathways responsible for DNA repair reinforcing the idea of a direct protective effect of the protein on DNA, in UV-C exposed cells, Dsup efficiently upregulates DNA damage repair genes. In conclusion, our data may help to delineate the different mechanisms by which the Dsup protein operates in response to different insults.

Serelaxin (RLX), the recombinant form of human Relaxin-2 hormone, protects the heart from the ischemia/reperfusion (I/R)-induced damage due to its anti-inflammatory, anti-apoptotic and antioxidant properties. RLX exerts its actions by binding to its specific RXFP1 receptor whereby it regulates multiple cellular transduction pathways. In this in vitro study we offer first evidence for the involvement of AMP kinase/Sirtuin1 (AMPK/SIRT1) pathway in the protection afforded by RLX against H/R-induced damage in H9c2 cells. Treatment of the H/R-exposed cells with RLX (17 nmol L−1) enhanced SIRT1 expression and activity. Inhibition of SIRT1 signaling with EX527 (10 µmol L-1) reduced the beneficial effect of the hormone on mitochondrial efficiency and cell apoptosis. Moreover, RLX upregulated AMPK pathway, as shown by the increase in the expression of phospho-AMPK active protein. Finally, AMPK pathway inhibition by Compound C (10 and 20 μmol L−1) abrogated the increase in SIRT1 expression induced by RLX, thus suggesting the involvement of AMPK pathway in this effect of RLX. The results of this study strengthen the concept that RLX exerts its cardioprotective effects against H/R-induced injury by multiple pathways which also include AMPK/SIRT1.

Lipofuscin accumulates with age as intracellular fluorescent granules originating from incomplete lysosomal digestion of phagocytosed and autophagocytosed material. The purpose of this review is to provide an update on the current understanding of the role of oxidative stress and/or lysosomal dysfunction in lipofuscin accumulation and its consequences, particularly for retinal pigment epithelium (RPE). Next, the fluorescence of lipofuscin, spectral changes induced by oxidation, and its contribution to retinal fluorescence are discussed. This is followed by reviewing recent developments in fluorescence imaging of the retina, and the current evidence on the prognostic value of retinal fluorescence for the progression of age-related macular degeneration (AMD), the major blinding disease affecting elderly people in developed countries. The evidence of lipofuscin oxidation in vivo, and the evidence of increased oxidative damage in AMD retina ex vivo lead to the conclusion that imaging of spectral characteristics of lipofuscin fluorescence may serve as a useful biomarker of oxidative damage which can be helpful in assessing the efficacy of potential antioxidant therapies in retinal degenerations associated with accumulation of lipofuscin and increased oxidative stress. Finally, amendments to currently used fluorescence imaging instruments are suggested, to be more sensitive and specific for imaging spectral char-acteristics of lipofuscin fluorescence.

The underlying mechanisms of secondary neuronal damage following intracerebellar hemorrhage are not yet clear. We aimed to study the possible mechanisms in the mediation of secondary neuronal damage following intracerebellar hemorrhage. ICbH was induced by collagenase type VII-S into mice in 2 phases (n=24/phase): 12 in control group, 12 in day 1 group, 12 in day 3 group and another 12 in day 7 group. All mice underwent locomotor assessment and subsequently sacrificed on day 1, day 3 and day 7 respectively. Cerebellum from phase one and phase two were taken to study morphological, immunohistochemistry and oxidative stress respectively. Mice behavior disturbed following ICbH at day 3 and y 7 as compared with control. Besides, NO increased-on day 1 post induction and suppressed on day 3 and 7. Expressions of SOD, CAT, nNOS, GPX1 and COX-2 were significantly raised on day 3. Morphological studies of the perihaematoma region and tissue showed neuronal damage occurred from day 1 onwards, peaked on day 3 and continued day 7. NO and expression of genes be correlating with morphological changes. Briefly, NO and oxidative stress has an important role in the cascade of secondary neuronal damage of the perihematomal region of ICbH.

Inhaled particulate matter (PM) is a key player in the millions of yearly deaths worldwide related to air pollution. The oxidative potential of PM provides an indication of its ability to promote an oxidative environment. When the human lungs are exposed to PM, the reactive oxygen species (ROS) generated in such oxidative environment, if excessive, may lead to cell damage via oxidative stress. Inflammation, endoplasmic reticulum stress, airway remodeling, and many different cell death modes (apoptosis, ferroptosis, pyroptosis, among others) can be triggered by oxidative stress via complex molecular pathways, which also involve the adaptive cellular response. But ROS can also directly interact with macromolecules such as proteins and lipids, as well as nucleic acids, having been reported to induce DNA damage and epigenetic modifications, which jeopardizes homeostasis. These facts have been extensively studied in in vitro models and confirmed in in vivo models.In this review, we delve beyond conventional assessments of airborne particles, discussing their oxidative potential and the PM-induced ROS-mediated cellular damage observed in in vitro models. The close link between oxidative stress and inflammation, and the manifestation of different cell death modes is highlighted by reviewing the latest literature. The effects of ROS on the balance of DNA damage and repair, carcinogenicity and epigenetics interplay are then analyzed. Finally, we expand on the latest reports on the antioxidants’ potential to counteract the deleterious effects of ROS, and disclose future perspectives for the topic.

Obesity is one of the factors leading to the development of atherosclerosis. This metabolic disorder is associated with an increased production of reactive oxygen species, which affect the oxidative stress level. The aim of this study was to evaluate oxidative/antioxidative status and to investigate the correlation between redox markers and anthropometric parameters and body composition in adult patients after myocardial infarction and in individuals without a cardiovascular event in the past. Descriptive data on socio-demographic, clinical, and anthropometric features and blood samples were collected and categorized into two equal groups: after myocardial infarction (study group (SG), n = 80) and without a cardiovascular event (control group (CG), n = 80). The oxidative/antioxidative status was assessed in plasma on the basis of total oxidative/capacitive status (PerOx), total antioxidative status/capacity (ImAnOx), and oxidized low-density lipoprotein (oxLDL). OxLDL was significantly higher in the CG group compared to the SG group (p = 0.02). No significant differences were found with regard to PerOx and ImAnOx values between the studied groups. Significant positive correlation between PerOx and percentage of adipose tissue (FM [%]) and body adiposity index (BAI) was found in the two studied groups. ImAnOx significantly positively correlated with VAI in SG and FM% in CG. OxLDL negatively correlated with body mass index and waist to hip circumference ratio in CG. The total oxidative/antioxidative status is related to the amount of adipose tissue and the BAI of the subjects. It was observed that it correlates more frequently with the visceral distribution of body fat.

The study investigated, in a rat model of low-level and moderate environmental exposure to cadmium (Cd; 1 or 5 mg Cd/kg diet, respectively, for 3-24 months), whether the co-administration of 0.1% extract from Aronia melanocarpa L. berries (AE) may protect against oxidative stress in the liver. The intoxication with Cd, dose- and duration-dependently, weakened the enzymatic antioxidative barrier (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase), decreased the concentrations of non-enzymatic antioxidants (reduced glutathione and total thiol groups), and increased the concentrations of oxidized glutathione, hydrogen peroxide, xanthine oxidase, and myeloperoxidase in this organ. These resulted in a decrease in the total antioxidative status (TAS), an increase in the total oxidative status (TOS), and development of oxidative stress in the liver (evaluated based on the index of oxidative stress calculated as the ratio of TOS and TAS). The administration of AE at both levels of Cd treatment significantly improved the enzymatic and non-enzymatic antioxidative barrier, decreased the concentration of pro-oxidants, and protected from the development of oxidative stress in the liver. In conclusion, consumption of aronia products may prevent Cd-induced destroying the oxidative/antioxidative balance and development of oxidative stress in the liver protecting against this organ damage.

Human exposure to carbon nanotubes (CNTs) can cause health issues due to their chemical–physical features and biological interactions. These nanostructures cause oxidative stress, also due to endogenous ROS production, which increases following mitochondrial impairment. The aim of this in vitro study was to assess the health effects, due to mitochondrial dysfunction, caused by a sub-chronic exposure to a non-acutely toxic dose of multi walled CNTs (raw and functionalised). The A549 cells were exposed to MWCNTs (2 µg mL^-1) for 36 days. Periodically, cellular dehydrogenases, pyruvate dehydrogenase kinase 1 (PDK1), cytochrome c release, permeability transition pore (mPTP) opening, transmembrane potential (Δψ m), apoptotic cells, and intracellular ROS were measured. The results, compared to untreated cells and to positive control formed by cells treated with MWCNTs (20 µg mL^-1), highlighted the efficiency of homeostasis to counteract ROS overproduction, but a restitutio ad integrum of mitochondrial functionality was not observed. Despite the tendency to restore, the mitochondrial impairment persisted. Overall, the results underlined the tissue damage that can arise following sub-chronic exposure to MWCNTs.

Increased screen time during the COVID-19 pandemic and the accelerated incorporation of technology into daily practices have directly contributed to the increased prevalence of eye disease. The human eye is not built for continual technological use and must adjust to exposure to digital screens. Overexposure to technology can result in eye strain and an increased risk of eye diseases such as myopia with complications later in life, including retinal tears, cataracts, and macular degeneration. As vision and ocular diseases become more prevalent, the study of eye diseases, including their causes and treatments, is especially relevant. There is a need to prevent ocular diseases before they become a burden to individuals, their families, and their communities by better understanding the pathophysiology of ocular diseases. Several ocular diseases are thought to be caused by imbalances in reactive oxygen species (ROS) and autophagy. ROS refers to a class of highly reactive oxygen-containing molecules that can undergo damaging reactions with other molecules in the cell. Autophagy is a cellular process of self-eating whereby damaged, harmful, or dead material in cells is broken down to maintain cellular homeostasis. This paper discusses the role of ROS and autophagy in the pathogenesis of computer vision syndrome (CVS), digital eye strain (DES), myopia, cataracts, glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), optic nerve crush injury (OCN), optic nerve gliomas, and retinoblastoma. Lifestyle changes such as limiting screen time, ensuring adequate exposure to evening sunlight, and using blue light protection measures or protective eyewear are important in the prevention of eye disease. Nutrition also contributes significantly to eye health. A balanced diet rich in vitamins and antioxidants may help to prevent ROS and autophagy imbalance-induced eye disease. Medical and surgical treatments become necessary when preventative measures fail. This paper also addresses how government measures to decrease the onset of eye disease, including targeted programs to increase access to fresh vegetables and fruits in food deserts, are a critical macro-level avenue to reduce eye disease prevalence in the US, which according to the National Eye Institute, costs $139 billion yearly.

Astaxanthin (ATX) is a carotenoid nutraceutical with a poor bioavailability due to its high lipophilicity. We tested a new tailored nano-droplet capable of solubilizing ATX in an oil-in-water micro-environment (LDS-ATX, manufactured by Lyotropic Delivery Systems (LDS)), for its capacity to improve ATX pharmacokinetic profile and anti-oxidant efficacy. We used liquid chromatography tandem mass spectrometry (LC-MS/MS) to compare the pharmacokinetic profile of ATX and LDS-ATX and protein carbonylation and lipid peroxidation assays to compare their basal and lipopolysaccharide (LPS)-induced oxidative damage. Our results show that only LPS-induced oxidative damage was corrected by ATX and LDS-ATX. While in the liver and muscle LDS-ATX was more efficacious than ATX in attenuating oxidative damage to both proteins and lipids, only oxidative damage to lipids was preferably corrected by LDS-ATX in the brain. These results strongly suggest improvement of ATX bioavailability and efficacy by the LDS-ATX nano-formulation.

Abstract: Alzheimer's Disease (AD) is a progressive uncurable neurodegenerative disease affect-ing millions worldwide. Various methods, including drug therapies and light emission diode (LED) irradiation, are promising alternatives for preventing and reducing the rapid progression of neurodegenerative diseases, also stimulating the reconstructing of neural tissue structures. In this study, we evaluated the neuroprotective and restorative effects of taurine combined with LED on human neuroblastoma cells (SH-SY5Y), under oxidative stress condition, a considerable modulator in AD. We evaluated LED at the wavelength of 660 nm and taurine under different concentrations before and after exposing SH-SY5Y cells to different concentrations of hydrogen peroxide (H2O2), assessing mitochondrial activity by the MTT colorimetric test and labeling live cell mitochondria by fluorescence using MitoTracker Orange. Cell viability was also evaluated by the trypan blue exclusion assay, and we verified cellular morphological structures by scan-ning electron microscopy (SEM). It was observed that neuroprotective effects are achieved by both LED and taurine when cells are exposed to them and later are stressed with H2O2. Compar-ing both agents, LED irradiation is sufficient to stimulate cell proliferation, representing an af-fordable candidate to contribute against neurodegeneration.

The biological aging, characterized by changing in metabolism and physicochemical properties of cells, has an impact on public health. Environment and lifestyle including factors like diet and physical activity seems to play a key role in healthy ageing. Several studies have shown that regular physical activity can enhance antioxidant defence mechanisms, including the activity of enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase. However, intense or prolonged exercise can also lead to an increase in ROS production temporarily, re-sulting in oxidative stress. This phenomenon is referred as "exercise-induced oxidative stress". The relationship between physical activity and oxidative stress in aging is complex and depends on various factors such as the type, intensity, duration, and frequency of exercise, as well as in-dividual differences in antioxidant capacity and adaptation to exercise. In this review, we ana-lyzed what is reported from several authors regarding the role of physical activity on oxidative stress in aging process as well as the role of hormesis and physical exercise as tools for preven-tion and treatment of sarcopenia, an aging related disease. Finally we reported what has recently been studied in relation to the effect of physical activity and sport on aging in women

Radiosensitivity, the susceptibility of cells to ionizing radiation, plays a critical role in understanding the effects of radiation therapy and exposure on tissue health and regeneration. Identifying characteristics that predict how a patient may respond to radiotherapy enables clinicians to maximize the therapeutic window. Limited clinical data suggested a difference in male and female radiotherapy outcomes. Radiotherapy for gastrointestinal malignancy is still a challenge due to intestinal sensitivity to radiation toxicity. In this manuscript we demonstrated sex specific differences in intestinal epithelial radiosensitivity. In mice model of abdominal irradiation, we observed significant increase in oxidative stress and injury in male compared to female. Lgr5+ve intestinal stem cells from male mice showed higher sensitivity to radiation induced toxicity. However, sex specific differences in intestinal radiosensitivity are not dependent on sex hormone as we demonstrated similar sex specific radiosensitivity differences in pediatric mice. In ex-vivo study we found that human patient derived intestinal organoid (PID) derived from male showed higher sensitivity to irradiation compared to female as evident from loss of budding crypt, organoid size, and membrane integrity. Transcriptomic analysis of human Lgr5+ intestinal stem cells suggested radiation induced upregulation of mitochondrial oxidative metabolism in male compared to female possible mechanism for radiosensitivity differences.

Recent years have seen an increased interest in the role of oxidative stress (OS) in pregnancy. Pregnancy inherently heightens susceptibility to OS, a condition fueled by a systemic inflam-matory response which culminates in an elevated presence of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the circulatory system. The amplified OS in pregnancy can trigger a series of detrimental outcomes such as underdevelopment, abnormal placental function, and a host of pregnancy complications, including pre-eclampsia, embryonic resorp-tion, recurrent pregnancy loss, fetal developmental anomalies, intrauterine growth restriction, and in extreme instances, fetal death. The body’s response to mitigate the uncontrolled increase in RNS/ROS levels involves trace elements that take part in non-enzymatic and enzymatic defense mechanisms, namely, copper (Cu), zinc (Zn), manganese (Mn), iron (Fe), and selenium (Se). Determination of ROS concentrations poses a challenge due to their short lifespan, prompting the use of marker proteins, including malondialdehyde (MDA), superoxide dis-mutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), lipid peroxidation (LPO), catalase (CAT), and glutathione (GSH). These markers, indicative of redox stress intensity, can offer indirect assessments of pregnancy complications. Given the limitations in conducting experimental studies on pregnant women, animal models serve as valuable substitutes for in-depth research. This review delves into the mechanism of OS in pregnancy and underscores the pivotal role of markers in its evaluation.

Why animals sleep is an outstanding open question. Information about the toxic byproducts of aerobic cellular respiration along with the analysis of patterns in animal size, sleep needs, dietary-type, metabolism, number of heart beats, transportation-network design, and transportation energetics/dynamics suggest that the function of sleep is to maximize the time an animal has to perform its life functions given the finite and constant number of lifetime heart beats it has. Sleep slows down metabolism, and the heart rate, thereby decreasing the load of toxic reactive oxygen species in the cell and extending the cell’s lifetime/proper-functioning. I argue that this is used to maximize the time an animal spends in its ‘effective environment’, which is defined as the period in the light cycle (day or night) where the essential life-functions of that animal (like finding resources, finding sex, hunting) are better achieved. Larger, slow-metabolizing animals need less sleep because their large-bodily-networks and slow metabolisms keep their heart rates relatively low, resulting in a lower rate of oxidative damage, and more relative time in the ‘effective environment’ to get their essential life-functions accomplished.

Oxidative stress occurs when cells are exposed to elevated levels of reactive oxygen species that could damage biological molecules. One bacterial response to oxidative stress involves disulfide bond formation either between protein thiols or between protein thiols and low-molecular-weight thiols. Bacillithiol was recently identified as a major low-molecular-weight thiol in Bacillus subtilis and related Firmicutes. Four genes (bshA, bshB1, bshB2 and bshC) are involved in bacillithiol biosynthesis. The bshA and bshB1 genes are part of a seven-gene operon (ypjD), which includes the essential gene cca, encoding CCA-tRNA nucleotidyltransferase. The inclusion of cca in the operon containing bacillithiol biosynthetic genes suggests that the integrity of the 3’ terminus of tRNAs may also be important in oxidative stress. Addition of the 3´ terminal CCA sequence by CCA-tRNA nucleotidyltransferase to give a mature tRNA and functional molecules ready for aminoacylation plays an essential role during translation and expression of the genetic code. Any defects in these processes, for example, the accumulation of shorter and defective tRNAs under oxidative stress, could exert a deleterious effect on cells. This review summarizes the physiological link between tRNA^Cys regulation and oxidative stress in Bacillus.

Fetal Alcohol Spectrum Disorders (FASD) represent a continuum of lifelong impairments resulting from prenatal exposure to alcohol, with significant global impact. The “spectrum” of disorders includes a continuum of physical, cognitive, behavioral, and developmental impairments, which can have profound and lasting effects on individuals throughout their lives impacting their health, social interactions, psychological well-being and every aspect of their lives. This narrative paper explores the intricate relationship between oxidative stress and epigenetics in FASD pathogenesis and its therapeutic implications. Oxidative stress, induced by alcohol metabolism, disrupts cellular components, particularly in the vulnerable fetal brain, leading to aberrant development. Furthermore, oxidative stress is implicated in epigenetic changes, including alterations in DNA methylation, histone modifications, and microRNA expression, which influence gene regulation in FASD patients. Moreover, mitochondrial dysfunction and neuroinflammation contribute to epigenetic changes associated with FASD. Understanding these mechanisms holds promise for targeted therapeutic interventions. This includes antioxidant supplementation and lifestyle modifications to mitigate FASD-related impairments. While preclinical studies show promise, further clinical trials are needed to validate these interventions' efficacy in improving clinical outcomes for individuals affected by FASD. This comprehensive understanding of the role of oxidative stress on epigenetics in FASD underscores the importance of multidisciplinary approaches for diagnosis, management, and prevention strategies. Continued research in this field is crucial for advancing our knowledge and developing effective interventions to address this significant public health concern.

This review focuses on the role of small extracellular vesicles in the pathophysiological mechanisms of retinal degenerative diseases. Many of these mechanisms are related or modulated by the oxidative burden of the retinal cells. It has been recently demonstrated that cellular communication in the retina involves extracellular vesicles and that their rate of release and cargo features might be affected by the cellular environment and in some instances also mediated by autophagy. The fate of these vesicles is diverse, and could end up in the circulation and be used as markers, or target neighbour cells modulating gene and protein expression and eventually also angiogenesis. Neovascularization in the retina promotes vision loss in diseases such as diabetic retinopathy and age-related macular degeneration. The importance of micro RNAs, either as small extracellular vesicles’ cargo or free circulating, on the regulation of retinal angiogenesis is also discussed.

Pesticides are among the most widely used synthetic chemicals worldwide to protect crops, but besides being beneficial, they pose several environmental and health issues. The present study evaluates toxic effects of acetamiprid (ACMP) in rat liver and kidney tissues. Rats were exposed to ACMP (21.7 mg/kg b.wt; 1/10th LD50) for 21 days. Oxidative stress generation, apoptotic progression, and structural changes were evaluated via biochemical assays, semi-quantitative PCR, western blotting, and histopathology. ACMP exposure significantly decreased body weight and altered relative organ weight in hepato-renal tissues. Significant oxidative stress was evident by increased oxidative injuries to lipids and proteins and alterations of endogenous anti-oxidative enzymes. The administration of ACMP upregulated mRNA expression of Bax and caspase-3, while downregulated the mRNA expression of Bcl-2 and released cytochrome c into the cytosol of the liver and kidney tissues. Likewise, exposure to ACMP caused severe degenerative changes in the histo-architecture of hepato-renal tissues. The results of the present study confirmed the toxicity of ACMP in rats’ liver and kidney tissues and emphasized the need for strict regulation and more mechanistic understanding to delineate the toxicity of ACMP in mammals.

One-step oxidative esterification of 2, 5-furandiformaldehyde (DFF) derived from biomass to prepare Dimethyl Furan-2, 5-dicarboxylate (FDMC) not only simplifies the catalytic process and increases purity of product, but also avoids the polymerization of 5-hydroxymethylfurfural (HMF) at high temperature condition. Gold supported on a series of acidic oxide, alkaline oxide and hydrotalcite were prepared by colloidal deposition to explore the effect of support on the catalytic activities. The Au/Mg3Al-HT catalyst exhibited the best catalytic activity in all catalysts, 97.8% selectivity of FDMC at 99.9% conversion of DFF. And this catalyst is suitable to oxidative esterification of benzaldehyde and furfural as well. X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and CO2 temperature programmed desorption (CO2-TPD) were performed to characterize the catalysts. The results indicated that the medium and strong basic sites in the heterogeneous catalysts benefited for the absorption of intermediate spices, further facilitated the oxidative esterification of aldehyde groups. While, neutral or acidic support tended to aldol condensation reaction. It was worth noting that basicity on the support surface reduce electronic state of the Au nanoparticle (Auδ-), thus enhance the catalytic selectivity of oxidative esterification. This finding demonstrated the support plays crucial role in oxidative esterification.

Abstract: Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress in DS is associated with neurodevelopmental defects, neuronal dysfunction, and the onset of dementia re-sembling Alzheimer's disease. Additionally, chronic oxidative stress contributes to cardiovascular diseases and certain cancers prevalent in DS individuals. This study investigates the impact of ageing on oxidative stress and liver fibrosis using a DS murine model (Ts2Cje mice). The liver in DS mice shows increased oxidative stress and impaired antioxidant defenses, as evidenced by reduced glutathione levels and increased lipid peroxidation. Furthermore, DS liver exhibits an altered in-flammatory response as measured by the expression of cytokines and heat shock proteins. DS liver also displays dysregulated lipid metabolism, indicated by altered expression of peroxisome prolif-erator-activated receptors and fatty acid transport proteins. Consistently, these changes might contribute to non-alcoholic fatty liver disease development, a condition characterized by liver fat accumulation. Finally, histological analysis of DS liver reveals increased fibrosis and steatosis, in-dicative of potential progression to liver cirrhosis. This finding highlights the increased risk of liver pathologies in DS individuals, particularly when combined with the higher prevalence of obesity and metabolic dysfunctions in DS patients. These results shed light on the liver's role in DS-associated pathologies and suggest potential therapeutic strategies targeting oxidative stress and lipid metabolism to prevent or mitigate liver-related complications in DS individuals.

Co/TiO2 catalysts with different cobalt loadings (3.8, 7.5 and 15 wt%) were prepared by impreg-nation method of Co(NO3)2 .6H2O over titania. Samples containing Co(NO3)2 .6H2O and TiO2 in stoichiometric proportions in order to obtain CoTiO3 and Co2 TiO4 phases were also synthesized. The effect of the calcination treatment at two different temperatures, 550 and 1150 °C was investigated. Characterizations by several techniques, such as XRD UV-vis-NIR, DRS, Raman and XPS were carried out. XRD showed the coexistence of three phases: CoTiO3; Co2TiO4 and Co3O4 after calci-nation at 550°C, while the calcination at high temperature (1150°C) leads to single-phase systems (CoTiO3 or Co2TiO4). Diffuse reflection and XPS spectroscopy showed that divalent cobalt occupies octahedral sites in the ilmenite phase and both tetrahedral and octahedral sites in the spinel phase. The catalytic performances of the prepared catalysts, calcined at the two different temperatures, were evaluated in the oxidative dehydrogenation reaction (ODH) of ethane to ethylene. The con-version values were almost comparable for all the samples, calcined at 550 °C, and comparable the ethylene selectivity were recorded, slightly higher only in the case of CoTiO3. The calcination at 1150°C did not modify the overall activity (ethane conversion values around 20%), however, the production of COx becomes more significant. The study examined the influence of the reaction mixture composition, specifically the presence of water, and reveals a slight increase in the yield of ethylene accompanied by a decrease in the overall catalyst activity. This behavior is likely attributed to an increase in the surface concentration of hydroxyl species (OH), resulting in heightened surface acidity.

This work is based on identifying the analysis techniques used to evaluate the antioxidant and anti-inflammatory effects using the zebrafish model. In this context, a literature review was performed with the Web of Science database. We used the terms zebra fish, antioxidant, anti-inflammatory, model, and Danio rerio. Fifty articles were reviewed, of which thirty-three were chosen to perform this review and were classified according to the source of plant extracts, compounds extracted from plants, chemical compounds, and other sources. This paper is an effort to provide a literature review on zebrafish models and elucidate their pros and cons to evaluate anti-inflamatory and antioxidant activity.

The effect of Gymnema Sylvestre supplementation on beta cell and hepatic activity was explored in an alloxan-induced hyperglycemic rat model. Adult rats were made hyperglycemic via a single inj. (i.p) of Alloxan (120mg/kg b.w). Gymnema Sylvestre was supplemented @250mg/kg and 500mg/kg b.w. Blood glucose levels were constantly monitored. After 21 days, rats were euthanized, and blood and tissues (pancreas and liver) were collected for biochemical, expression, and histological analysis. One-way ANOVA was used to compare the means of different treatment groups. Gymnema Sylvestre significantly reduced blood glucose levels with a subsequent increase in plasma insulin levels in a dosage-dependent manner. Total oxidant status (TOS), malondialdehyde, LDL, VLDL, ALT, AST, triglyceride, total cholesterol, total protein, C-reactive protein, and cortisol levels were reduced significantly in alloxan-treated hyperglycemic rats supplemented with Gymnema Sylvestre as compared to control. Significantly raised paraoxonase, arylesterase, albumin, and HDL levels were also observed in Gymnema Sylvestre supplemented hyperglycemic rats. Increased mRNA expression of Ins-1, Ins-2, Gck, Pdx1, Mafa, and Pax6 were observed, while decreased expression of Cat, Sod1, Nrf2, and NF-kB was observed in the pancreas. Whereas increased mRNA expression of Gck, Irs1, SREBP1c, and Foxk1 and decreased expression of Irs2, ChREBP, Foxo1, and FoxA2 were observed in the liver. The current study indicates the potent effect of Gymnema Sylvestre on the transcription modulation of the insulin gene in the alloxan-induced hyperglycemic rat model. Enhanced plasma insulin levels further help to improve hyperglycemia-induced dyslipidemia through transcriptional modulation of hepatocytes.

An imbalance in any metabolic system can be traced to its homeostasis. When homeostatic environment is not attainable then there will be a response from the body. A new shift has emerged, “the negative feedback effect of high fructose consumption;” more pain than gain. The human metabolic system daily combat fructose sugar metabolism which emanates from high consumption. This inadvently lead to a chronological series of complications arising from the feedback. These feedbacks play pivotal roles in skeletal muscle damage and other body frameworks, it also fosters toxic advanced glycation end products (AGEs), factors that impose and inflict damaging effects to the body`s energy currency and serious threat to health. These damages are missed or overlooked because of early nonspecific physiological symptoms. High level of fructose has both long- and short-term effects on human metabolic processes. These effects which are majorly through the production of reactive oxygen species (ROS) and other free radicals, are felt in the disruption of biomolecules such as causing DNA mutation, lipid peroxidation etc. these effects in turn lead to various diseases such as cancer, diabetes, atherosclerosis, and other health issues. In this review, we will focus on the damaging effects this sugar has on human health and the present solutions being applied. We will also look at the next step in combatting and controlling these negative feedbacks.

In present work, the effects of bioflavonoids (ginkgetin and sciadopitysin) on stimulus-induced superoxide generation, tyrosyl and serine/threonine phosphorylation of proteins in human neutrophils, and the translocation of cytosolic compounds (p47phox, p67phox and Rac) to cell membrane were studied, which were isolated from the needles of Taxus media var. Hicksii. Meanwhile, three normal flavonoids (apigenin, quercetin and isoquercetin) were involved as contrasts. The results indicated that ginkgetin and sciadopitysin were capable of concentration-dependently inhibitory effects on the superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP), arachidonic acid (AA) and phorbol-12-myristate 13-acetate (PMA). And they also suppressed fMLP- and AA- induced tyrosyl or PMA-induced serine/threonine phosphorylation and the translocation of cytosolic compounds (p47phox, p67phox and Rac) to cell membrane, which were in parallel with the suppression of the stimulus-induced superoxide generation. The effect of these compounds on the radical-scavenging was also investigated. Ginkgetin and sciadopitysin did not show remarkable effect on DPPH radical-scavenging activity, and they didn’t display the radical-scavenging activity on superoxide anion generated by phenagine methoxysulfate (PMS)-NADH system. Apparently, ginkgetin and sciadopitysin had great performance in pharmacological value and they are worthy of in-depth study.

Astaxanthin (AX) is a carotenoid that exerts potent antioxidant activity and acts in the lipid bilayer. This study aimed to investigate the effects of AX on muscle atrophy-mediated disturbance of mitochondria that have a lipid bilayer. Tail suspension was used to establish muscle- atrophied mouse models. AX diet fed to tail-suspension mice prevented loss of muscle weight and decreased myofiber size in the soleus muscle. Additionally, AX improved down-regulation of mitochondrial respiratory chain complexes II and III in the soleus muscle after tail suspension. To confirm the AX phenotype in the soleus muscle, we examined its effects on mitochondria using Sol8 myotubes derived from the soleus muscle. We found that AX was preferentially detected in the mitochondrial fraction; it significantly suppressed mitochondrial complex III-driven production of reactive oxygen species in Sol8 myotubes. Moreover, AX inhibited the activation of caspase 3 via inhibiting the release of cytochrome c into the cytosol in antimycin A-treated Sol8 myotubes. These results suggested that AX inhibited mitochondrial oxidative stress through a mitochondria-mediated apoptosis pathway and thus prevented muscle atrophy.

Charcot-Marie-Tooth disease is a hereditary polyneuropathy caused by mutations in Mitofusin-2 (MFN2), a GTPase in the outer mitochondrial membrane involved in the regulation of mitochondrial fusion and bioenergetics. Autosomal-dominant inheritance of a R94Q mutation in MFN2 causes the axonal subtype 2A2A which is characterized by early onset and progressive atrophy of distal muscles caused by motoneuronal degeneration. Here, we studied mitochondrial shape, respiration, cytosolic and mitochondrial ATP content as well as mitochondrial quality control in MFN2-deficient fibroblasts stably expressing wildtype or R94Q MFN2. Under normal culture conditions, R94Q cells had slightly more fragmented mitochondria but a similar mitochondrial oxygen consumption, membrane potential and ATP production as wildtype cells. However, when inducing mild oxidative stress 24 h before analysis using 100 µM hydrogen peroxide, R94Q cells exhibited significantly increased respiration but decreased mitochondrial ATP production. This was accompanied by increased glucose uptake and an upregulation of hexokinase 1 and pyruvate kinase M2 suggesting increased pyruvate shuttling into mitochondria. As these changes coincided with decreased levels of PINK1/Parkin-mediated mitophagy in R94Q cells, we conclude that the disease-causing R94Q mutation in MFN2 causes uncoupling of mitochondrial respiration from ATP production by a less efficient mitochondrial quality control triggered by oxidative stress.

The objective of this study was to perform a systematic review and meta-analysis of the articles that addressed the effect BA or carnosine supplementation on physical exercise (PE)-induced oxidative stress (OS). Before May 2018 we searched throughout PubMed, CAPES Periodic and SPORTDiscus human model peer review, randomized control studies with chronic BA or carnosine supplementation on PE-induced OS. A total of 128 citations were found. Only four articles met criteria for inclusion. All four studies used healthy young sedentary, recreationally active or athletic participants. After a chronic BA or carnosine supplementation, the studies evaluated PE-induced OS both immediately and several hours after exercise (0.5 to 48 h). In response to PE-induced OS, when compared to placebo, BA/carnosine supplementation increased total antioxidant capacity [TAC; Effect Size (ES) = 0.35, 95% Confidence Interval (CI) 0.06 to 0.65, p = 0.02] and glutathione (GSH; ES = 0.75, 95% CI 0.32 to 1.19, p = 0.0007) concentrations while decreased direct OS markers (ES = −1.19, 95% CI −1.48 to −0.80, p < 0.01) and superoxide dismutase (SOD) activity (ES = − 0.58, 95% CI −1.10 to −0.06, p = 0.03). BA or carnosine supplementation did not prevent the increase in indirect OS markers (ES: 0.06, 95% CI −0.38 to 0.500, p = 0.80). In humans, following PE-induced OS, initial treatment trials of BA or carnosine supplementation seemed to increase TAC and GSH concentrations, while decreasing SOD activity. Also, albeit mitigating the acute increase in direct OS markers (reactive nitrogen and oxygen species), treatment did not decrease measured values of indirect OS markers (peroxidation or molecule oxidation).

Studies have shown that aerosols generated from flavored e-cigarettes contain Reactive Oxygen Species (ROS), promoting oxidative stress-induced damage within pulmonary cells. Our lab investigated the ROS content of e-cigarette vapor generated from disposable vape bars, a product exempt from the Federal Drug Enforcement Agency’s (FDA) 2020 flavor ban. Specifically, we analyzed vape bars belonging to multiple flavor categories (Tobacco, Minty Fruit, Fruity, Minty/Menthol, Desserts, and Drinks), manufactured by various vendors and of various nicotine concentrations (0-6.8%). Aerosols from these flavored vape bars were generated by a single puff aerosol generator and individually bubbled through a fluorogenic solution to detect and semi-quantify ROS in H2O2 equivalents generated by the vape bars. We compared and contrasted the ROS levels generated by each flavor as an indirect determinant of oxidative stress potential by these disposable vape bars. Our results showed that ROS concentration (μM) of aerosols produced from the vape bars varied significantly between different flavors and a function of nicotine concentration. Likewise, our results suggest that flavoring chemicals and nicotine concentration play a role in alerting ROS production in e-cigarette aerosols. Our study provides insight into the differential health effects of flavored disposable vape bars and the need for their regulation.

Probiotic feed additives have attracted considerable research interest in recent years because the effectiveness of probiotics can differ across microbial strains and the supplemented macroorganisms. The present study was conducted on 16 lambs divided into two groups (C - control and E - experimental). The examined lambs were aged 11 days at the beginning of the experiment and 40 days at the end of the experiment. The diet of group E lambs was supplemented with a multi-strain probiotic formulation (Lactobacillus plantarum AMT14, Lactobacillus plantarum AMT4, Lactobacillus rhamnosus AMT15, and Bifidobacterium animalis AMT30), whereas group C lambs did not receive the probiotic additive. At the beginning of the experiment (day 0) and on experimental days 15 and 30, blood was sampled from the jugular vein to determine and compare: phagocytic activity (PHAGOTEST) and oxidative metabolism (PHAGOBURST) of peripheral blood granulocytes and monocytes by flow cytometry. An analysis of the phagocytic activity of granulocytes and monocytes revealed significantly higher levels of phagocytic activity (expressed as the percentage of phagocytic cells and mean fluorescence intensity) in lambs administered the multi-strain probiotic formulation than in the control group. The probiotic feed additive also exerted a positive effect on the oxidative metabolism of both granulocytes and monocytes (expressed as the percentage of oxidative metabolism and mean fluorescence intensity) after stimulation with Escherichia coli bacteria and with PMA (4-phorbol-12-β-myristate-13-acetate).

The changes in the properties of three biological events, that occur with cerebral aging, are discussed. These adverse changes already begin to develop early in mid-life and gradually become more pronounced with senescence. Essentially, they are reflections of the progressive decline in effectiveness of key processes, resulting in the deviation of essential biochemical trajectories to ineffective and ultimately harmful variants of these programs. The emphasis of this review is the major role played by mitochondria in such transition of these three important processes toward more deleterious variants as brain aging proceeds. 1. The immune system. The shift away from an efficient immune response to a more unfocused, continuing inflammatory condition. Such a state is both ineffective and harmful. 2. Reactive oxygen species are important intracellular signaling systems. Also, microglial phagocytic activity utilizing short lived reactive oxygen species contribute to the removal of aberrant or dead cells and bacteria. These processes are transformed into an excessive, untargeted and persistent generation of pro-oxidant free radicals (oxidative stress). 3. The normal efficient neural transmission is modified to a state of undirected, chronic low-level excitatory activity. Each of these changes is characterized by the occurrence of continuous activity that is inefficient and diffuse. The signal/noise ratio of several critical biological events is thus reduced as beneficial responses are gradually replaced by their impaired and deleterious variants.

The flavonoid silymarin (SMN) has been widely used in preclinical and clinical studies to treat various types of cancer, either alone or in combination with chemotherapy agents. Herein, we investigated the therapeutic efficacy of SMN and its combination with capecitabine (CAP) and irinotecan (IRI) in a mouse model of colon cancer. A modified diet supplemented with SMN (2500 ppm) with mono- and combined therapy of CAP and IRI were used following 1, 2 dimethylhydrazine (DMH)-induced colon cancer. The lipid profile, liver function tests, and cytokine levels were measured. Additionally, the lipid peroxidation and inflammation indices as well as the antioxidant activities were examined. Eventually, western blotting analysis for colonic BAX and Bcl-2 levels and histopathological examination of colon sections were carried out. SMN alone and in combination with the chemotherapeutic agents could attenuate the DMH-induced hyperlipidemia and elevated liver function enzyme levels. SMN supplementation with chemotherapy agents could also improve antioxidant activity and reverse the elevated levels of lipid peroxidation and inflammatory markers. Furthermore, significant upregulation of BAX and downregulation of Bcl-2 were observed. Besides, carcinogen-induced polyp multiplicity, dysplastic, and inflammatory changes were ameliorated considerably by treatment regimens. Our results showed that the potential anticancer properties of SMN could enhance the therapeutic effects of chemotherapy agents and reduce hepatotoxicity.

Polyphenolic compounds, encompassing flavonoids (e.g., quercetin, rutin, cyanidin) and non-flavonoids (e.g., gallic acid, resveratrol, curcumin), show several health-related beneficial effects, which include antioxidant, anti-inflammatory, hepatoprotective, antiviral, and anticar-cinogenic properties, as well as the prevention of coronary heart diseases. Polyphenols have been also investigated for their counteraction against adverse effects of common anticancer chemo-therapeutics. This review examines the outcomes of clinical studies (and related preclinical data) over the last ten years, with a focus on the use of polyphenols in chemotherapy as auxiliary agents acting against oxidative stress toxicity induced by antitumor drugs. While further clinical studies are needed to establish adequate doses and optimal delivery systems, the improvement in pol-yphenols’ metabolic stability and bioavailability, through implementation of nanotechnologies currently being investigated, could improve therapeutic applications of their pharmaceutical or nutraceutical preparations in tumor chemotherapy.

Previous studies detail that the different blood groups are associate to incidence of oxidative stress-related diseases such as certain carcinomas. Bioactive compounds represent an alternative to prevent this oxidative-stress. The aim of this study was to elucidate the impact of blood groups on the erythroprotective potential of Fucoxanthin, β-Carotene, gallic acid, quercetin, and ascorbic acid as therapeutic agents against oxidative-stress. The impact of ABO blood groups on the erythroprotective potential was evaluate by the elucidated antioxidant capacity, blood biocompatibility, blood susceptibility and erythroprotective potential (membrane stabilization, in vitro photostability and antihemolytic activity). All antioxidant tested exhibited a highest potent antioxidant capacity and presented the ability to inhibit ROO•-induced oxidative-stress without compromising the cell membrane, providing an erythroprotective effect dependent on the blood group. Effect that increased in the presence of antigen A. This result could be key to the prevention of carcinomas associated with antigen A, such as breast and skin cancer. These results revealed a probable relationship between the different erythrocyte antigens with the erythroprotective potential, highlighting the importance of bio-targeted drugs for groups mostly susceptible to certain chronic-degenerative pathologies. These compounds could be applied as additive, nutraceutical or encapsulated to improve its bioaccessibility.

Background: As the impacts of diabetes-induced reproductive damage are now evident in young people, we are now in an urgent need to devise new ways to protect and enhance the reproductive health of diabetic people. The purpose of this study was to assess the protective impact of enalapril (an ACE inhibitor) and paricalcitol (a vitamin D analogue) alone and in combination, on streptozotocin (STZ) diabetes-induced testicular dysfunction in rats. Material and methods: This study was carried on 50 male Sprague-Dawley rats; 10 normal rats were allocated as non-diabetic control group. 40 rats developed diabetes after receiving a single dose of STZ, then the diabetic rats were divided into four groups of equivalent number assigned as diabetic control, enalapril treated, paricalcitol treated, in addition to combined enalapril and paricalcitol treated groups. The effects of mono and combined therapy with paricalcitol and enalapril on testicular functions, sperm activity, glycemic state oxidative stress and inflammatory parameters as well as histopathological examination were assessed when compared to the normal and diabetic control rats. Results: As a result of diabetes induction, epididymal sperm count, sperm motility, serum levels of testosterone, follicle stimulating hormone (FSH) as well as luteinizing hormone (LH) and the antioxidant enzyme activities were significantly decreased, while abnormal sperm (%), insulin resistance, nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6) as well as tumor necrosis factor-α (TNF-α) were significantly increased, along with sever distortion of testicular structure. Interestingly, treatment with paricalcitol and enalapril either alone or in combination significantly improved the sperm parameters, increased antioxidant enzyme activities in addition to serum levels of testosterone, FSH and LH, reduced insulin resistance, IL-6 and TNF-α levels and finally ameliorated the diabetes-induced testicular oxidative stress and histopathological damage with somewhat superior effect for paricalcitol monotherapy and combined therapy with both drugs than monotherapy with enalapril alone. Conclusion: Monotherapy with paricalcitol and its combination therapy with enalapril has a somewhat superior effect in improving the diabetes-induced testicular dysfunction (most probably as a result of their hypoglycemic, antioxidant, anti-inflammatory and anti-apoptotic properties), than monotherapy with enalapril alone in male rats, recommending a synergistic impact of both drugs.

Bees have long been used as a bioindicator of environmental quality. They have the capacity to bio-accumulate various pollutants in cities such as PAHs and heavy metals, but they are also very sensitive to other pollutants in rural areas such as pesticides. The lethal and sub-lethal impacts of pesticides on bees have been extensively studied. However, studies often focus on a single molecule at a same time and rarely on a cocktail of pesticides. The oxidant stress in response to metals and NOx was also measure, but no studies were engaged on the impact of PAHs on honeybees. The aim of this study was to measure the oxidative stress in bees in response to the chronic ingestion of a mixture of pesticides (representative of pollutants in rural areas) on the first hand and a mixture of PAHs (representative of pollutants in urban areas) on the other hand, compared to a control group. We also wanted to determine whether this tool is effective in detecting environmental measures aimed at reducing pollution in urban and rural areas.

Bifenthrin is a synthetic pyrethroid insecticide. It is used worldwide against different agricultural pests. Nervous system (NS) is the primary target organ for the pyrethroid group of insecticide which causes hyper excitation. The aim of this study to determine the effects of bifenthrin on the brain of rabbits. The animals were treated for 14 days with three different doses (1/5th, 1/10th and 1/15th of LD50) of bifenthrin. Neurotransmitters and Histopathological alterations were observed at the end of the experiments. Neurochemical parameters were checked 24 hours after the last dose. Significant changes in the level of biogenic amines were observed. The levels of epinephrine (EPN), dopamine (DA), 3, 4 dihydroxyphenylacetic acid (DOPAC) were decreased as compared to controls group with the increase in insecticide. However, norepinephrine (NE) and homovanillic acid (HVA) levels were found to be significantly higher than those of the controls. A significant reduction in the activity of the acetyl cholinesterase enzyme was found in the frontal cortex’s erythrocyte, plasma and brain of rabbit with the increase in administered bifenthrin. The oxidative stress showed significantly decrease in the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and glutathione S- transferase (GST) with the increase in dose of bifenthrin. Histopathological study of brain tissues showed normal GC (glial cells) and NC (neuronal cells) in the frontal cortex of brain tissue of control groups while the treated groups showed evacuation (odema), elongation of pyramidal nucleus, glial cell damage and brain haemorrhage.

Galanthus elwesii Hook is an important plant species of the Amaryllidaceae family and is used for medicinal purposes with its valuable bioactive compounds. The present study was conducted to investigate the effects of foliar salicylic acid (SA) and zinc (Zn) treatments on proline, carotenoid, chlorophyll content and anti-oxidant enzyme activity in G. elwesii. The ascorbate peroxidase (APX), catalase (CAT) enzyme activity, and protein contents were determined with ascorbate oxidation, hydrogen peroxide (H2O2), and Bradford experiments, respectively. The plants were treated with three different concentrations of SA (0.5, 1, and 2 mM) and, and Zn (40, 80, and 120 mM) were compared with the control. Fresh leaves were harvested in the study. APX (3.99 ± 0.58 EU/mg protein) and CAT (154.64 ± 4.10 EU/mg protein) were obtained from Zn 80 and 120 mM treatments at the highest level, respectively. Proline, chlorophyll b, and carotenoid content increased 12.4, 1.54 and 3.95-fold, respectively, in 0.5 mM SA treatments when matched with control group. It was found that increasing doses of SA and Zn increased the content of malondialdehyde (MDA), but this was not at a significant level. The total chlorophyll content increased 2.27-fold in Zn 120 mM + SA 2 mM treatment and the chlorophyll content increased 2.41-fold in Zn 40 mM + SA 1 mM treatment.

Atherosclerosis (AS) is an age-related disease. Mitochondria and telomere links have been considered to play important roles in AS. PinX1 is a potent and highly conserved endogenous telomerase inhibitor. However, the role of pinX1 in AS and its role in oxidative stress have not been reported. In order to investigate the role of pinX1 in AS, we established a classical AS mice model in the present work and increased pinX1 protein expression using pinX1 overexpression adeno-virus by tail vein injection. Then, red-oil O and HE staining were employed to evaluate the severity of AS. Serum lipid profile and oxidative stress were also detected by using its specific chemical testing kit. The results indicated that high-fat diet (HFD) markedly decreased pinX1 and increased p66shc protein expression, whereas overexpression of pinX1 protein expression in mice produced the opposite results. In addition, pinX1 significantly minimized plaque area and alleviated the abnormal serum lipid profile. By using Western blot and Biochemical assay kits, overexpression of pinX1 decreased p66shc and MMP-9 protein expression and reduced oxidative stress. This study showed pinX1 can inhibit p66shc, MMP-9, and related oxidative stress, pinX1 may be considered as a new candidate target for the treatment of AS.

Phototherapy is an efficient strategy to respond to oxidative stress and has been in the spotlight in various therapeutic fields through its biological effect, but the exact molecular mechanism has not yet been established. As a result of irradiating RAW264.7 cells with a 630 nm or 850 nm LED with an energy intensity of 0.01J/cm2, cell viability was increased depend on the irradiation time. After H2O2 was added, 630 nm or 850 nm LEDs were irradiated for 10 min or 40 min to increase cell viability by about 1.7- or 1.6-fold, respectively. In addition, 630nm or 850nm LED irradiation showed a significant ROS scavenging effect and significantly reduced TUNEL-positive cells by 45.7% and 37.8%, respectively, compared to cells treated only with H2O2. In the result of flow cytometry, the number of cells in the late apoptosis stage was about 2.3- and 1.8-fold lower than that of the cells treated with H2O2 only, but there was no significance. The Bax/Bcl-2 ratio of cells irradiated with 630 nm or 850 nm LED was significantly lower than that of cells treated with H2O2 only, and the expression of procaspase-3 and cleaved PARP was also significantly expressed in the direction of suppressing cell death. In conclusion, the ROS scavenging activity by 630 nm or 850 nm LED irradiation, leading the expression of cell death pathway proteins in the direction of inhibiting cell death.

The ameliorative effect ethanolic extract of M. oleifera (MO) leaves in combination of curcumin against seizures, cognitive impairment & oxidative stress PTZ-induced kindled rats. Molecular docking was performed to predict the potential phytochemical of MO and curcumin against Epilepsy. The effect of pretreatment with leaves of M. oleifera ethanolic extracts (MOEE) (250, 500mg/kg, orally), curcumin (200 and 300 mg/kg, orally), valproic acid used as standards (100mg/kg) and combined effect of MOEE (250mg/kg) and curcumin (200mg/kg) at low dose, on pentylenetetrazole (PTZ)-induced kindling. For the development of kindling the individual Wistar rats (Male) were injected pentyletetrazole (40 mg/kg, i.p.) on every alternate day. Molecular Docking has been done by AutoDock4.2 tool to merge the ligand orientations in the binding cavity. From the RCSB website, the crystal structure of Human Glutathione reductase (PDB ID: 3DK9) was obtained. Curcumin and MOEE showed dose-dependent effect. The combined effects of leaves of MOEE & curcumin significantly improved the seizure score and decreased the number of myo-clonic jerks in compare with standard dose of valproic acid. PTZ kindling induced a significant oxidative stress and cognitive impairment which was reversed by pretreatment with MOEE & curcumin. Glutathione reductase (GR) is an enzyme, which plays key role in the cellular control of reactive oxygen species (ROS). Therefore, activating GR can uplift the antioxidant property, which leads to the inhibition of ROS induced cell death in brain. The combination of ethanolic extract of M. oleifera (MOEE) leaves and curcumin have shown better result than any other combination for antiepileptic effect by virtue of antioxidant effects. As per docking study showed that the chloro-genic acid and quercetin is treated with the combination of curcumin can be much more potential.

Oxidative stress (OS) is a condition in which there is an excess of reactive oxygen species (ROS) in the body, which can lead to cell and tissue damage. This occurs when there is an overproduction of ROS or when the body's antioxidant defense systems are overwhelmed. Quercetin is part of a group of compounds called flavonoids. It is found in high concentrations of vegetables, fruits, and other foods. Over the past decade, a growing number of studies have highlighted the therapeutic potential of flavonoids to modulate neuronal function and prevent age-related neurodegeneration. Therefore, quercetin has been shown to have antioxidant, anticancer, and anti-inflammatory properties, both in vitro and in vivo. Due to its antioxidant character, quercetin alleviates oxidative stress, thus improving cognitive function, reducing the risk of neurodegenerative diseases. On the other hand, quercetin can also help support the body's natural antioxidant defense systems, thus being a potentially practical supplement for managing oxidative stress. This review focuses on experimental studies supporting the neuroprotective effects of quercetin in Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington's disease (HD) and epilepsy.

Excessive intake of fluoride, one of the trace elements to maintain health, leads to liver injury. Tetramethylpyrazine (TMP) is a kind of traditional Chinese medicine monomer with good antioxidant and hepatoprotective function. The aim of this study was to investigate the effect of TMP on liver injury induced by acute fluorosis. A total of 60 1-month-old male Institute of Cancer Research mice without carriage of pathogenic bacteria were selected. All mice were fed adaptively for one week, and then randomly divided into 5 groups: control (K) group, model (F) group, low-dose (LT) group, medium-dose (MT) group and high-dose (HT) group. The control and model group were given distilled water, while 40 mg/kg (LT), 80 mg/kg (MT) and 160 mg/kg (HT) TMP were fed by gavage for two weeks with the maximum gavage volume of mice is 0.2ml/10g/d. Except for the control group, all groups were given fluoride (35 mg/kg) by intraperitoneal injection on the last day of the experiment. The results of this study showed that compared with the model group, TMP alleviated the pathological changes of liver induced by fluoride and improved the ultrastructure of liver cells; TMP significantly decreased the levels of ALT, AST and MDA (P <0.05), and increased the levels of T-AOC, T-SOD and GSH (P <0.05). The results of mRNA detection showed that TMP significantly increased the mRNA expression levels of Nrf2, HO-1, CAT, GSH-Px and SOD in liver compared with model group (P <0.05). In conclusion, TMP can inhibit oxidative stress by activating Nrf2 pathway and alleviate liver injury induced by fluoride.

Repeated exposure to environmental ozone causes a chronic state of oxidative stress. This state is present in chronic degenerative diseases and induces a loss of control of the inflammatory response. The dysfunction of redox system and failures in control the inflammatory responses are involved in a vicious circle that maintains and increases the degenerative process. Intestine also responds to secondary reactive species formed by exposure to ozone doses, generating noxious stimuli that increase degenerative damage. This review aims to elucidate how environmental pollution, mainly by ozone, induces a state of chronic oxidative stress with the loss of regulation of the inflammatory response, both in the intestine and in the brain, where the functionality of both structures is altered and plays a determining role in some neurodegenerative and chronic degenerative diseases. For this purpose, we searched for information on sites like the Cochrane Library Database, PubMed, Scopus, and Medscape. Reviewing the data published, we can conclude that environmental pollutants are a severe health problem. Ozone pollution has different pathways of action, both molecular and systemic, and participates in neurodegenerative diseases such as Parkinson's and Alzheimer's disease as well in bowel diseases as Inflammatory Bowel Disease, Crohn's Disease and Irritable Bowel Syndrome.

Neurodegeneration is an age-dependent progressive phenomenon with no defined cause. Aging is the main risk factor for neurodegenerative diseases. During aging, activated microglia undergoes phenotypic alterations that can lead to neuroinflammation, which is well accepted event in the pathogenesis of neurodegenerative diseases. Several common mechanisms are shared by genetically or pathologically distinct neurodegenerative diseases, such as excitotoxicity, mitochondrial deficits and oxidative stress, protein misfolding and translational dysfunction, autophagy and microglia activation. Progressive loss of neuronal population due to increased oxidative stress leads to neurodegenerative diseases mostly due to the accumulation of dysfunctional mitochondria. Mitochondrial dysfunction and excessive neuroinflammatory responses are both sufficient to induce pathology in age-dependent neurodegeneration. Therefore, mitochondrial quality control is key determinant for the health and survival of neuronal cells in the brain. Research has been primarily focused to demonstrate the significance of neuronal mitochondrial health, despite the important contributions of non-neuronal cells that constitutes significant portion of the brain volume. Moreover, mitochondrial morphology and function are distinctly diverse in different tissues; however, little is known about their molecular diversity among cell types. Mitochondrial dynamics and quality in different cell types markedly decides the fate of overall brain health, therefore it is not justifiable to overlook non-neuronal cells and their significant and active contribution in facilitating overall neuronal health. In this review article, we aim to discuss the mitochondrial quality control of different cell types in the brain and how important and remarkable is the diversity and highly synchronized connecting property of non-neuronal cells in keeping the neurons healthy to control neurodegeneration.

Consumption of poultry meat is higher than red meat due to easy availability, good taste, low cost and palatability. Significant improvement in meat yield and growth rate of broiler chicken has been brought about with the help of genetic selection of desirable traits. The present study was conducted to comparatively evaluate the chronic effect of domestic and broiler chicken meat consumption on male hypothalamic pituitary gonadal axis, lipid profile and oxidative stress on postnatal male rats. Rats were divided into five groups: control, B1, B2, D1 and D2 groups and were fed with 0.17g and 0.34g of broiler and domestic chicken meat from postnatal day 21 to PND90.The significant elevated body weight and weight gain in B2 group (P<0.01), minor change in B1 and D40 group (P<0.05) were detected. In gonadosomatic index absolute and relative epididymis weight, weight of seminal vesical and Prostate weight was significantly augmented in B2 compared to control and D2. Kidney and liver weight in B1, B2 was markedly elevated and minor change in D2 groups. ROS level in B2 was significantly higher than other experimental groups. Serum level of FSH, LH, testosterone, estradiol and low density lipoprotein was significantly elevated in B2 compared to control and D2. In B2 rats fed with 0.34g broiler meat exhibited a marked decreased seminiferous tubule diameter, epithelial height and increased lumen diameter changes that were more prominent compared to rats fed with 0.34g domestic chicken meat. Conclusively chronic administration of broiler meat induces marked alteration in reproductive system, testicular morphology, sexual hormones and oxidative stress in postnatal Sprague Dawley male rats compared to domestic chicken meat.

Cryptococcus neoformans is a human multidrug-resistant yeast with high mortality rates in immunocompromised patients. Recently, the synthetic peptide Mo-CBP3-PepII emerged as a potent anticryptococcal molecule with an MIC50 at low concentration. Here, the mechanisms of action of Mo-CBP3-PepII were deeply analyzed to provide new information about how it led C. neoformans cells to death. Light and fluorescence microscopies, analysis of enzymatic activities, and proteomic analysis were employed to understand the effect of Mo-CBP3-PepII on C. neoformans cells. Light and fluorescence microscopies revealed Mo-CBP3-PepII induced the accumulation of anion superoxide and hydrogen peroxide in C. neoformans cells. In addition to a reduction in the activity of superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT) in the cells treated with Mo-CBP3-PepII. In the presence of Ascorbic acid (AsA), no ROS were detected and Mo-CBP3-PepII lost the inhibitory activity against C. neoformans. Yet, Mo-CBP3-PepII inhibited the activity of lactate dehydrogenase (LDH), ergosterol biosynthesis, and induced the decoupling of cytochrome c from the mitochondrial membrane. Proteomic analysis revealed a reduction in the abundance of proteins related to energetic metabolism, DNA and RNA metabolism, pathogenicity, protein metabolism, cytoskeleton, and cell wall organization and division. Our findings indicated that Mo-CBP3-PepII might have multiple mechanisms of action against C. neoformans cells, mitigating the development of resistance and thus being a potent molecule to be employed in the production of new drugs against C. neoformans infections.

Chrysoeriol (CHE) is a flavonoid substance that exists in many plants and has various physiological and pharmacological effects, including anti-inflammatory, antioxidant, anti-tumor, and protective activity, especially for the cardiovascular system and liver. This study aimed to analyze the results and possible mechanisms of CHE on early porcine embryo development. Adding CHE to the culture media can improve the development quality of early porcine embryos. CHE significantly increased the blastocyst rate and total cell number of embryos in vitro. The apoptosis of blastocyst in CHE-treated culture also decreased significantly compared with untreated culture. Furthermore, CHE downregulated intracellular reactive oxygen species (ROS) and increased glutathione (GSH) in embryos. CHE was also shown to improve the activity of mitochondria and inhibit the occurrence of autophagy. In addition, antioxidant-related genes (SOD1, SOD2, and CAT) and cell pluripotency-related genes (SOX2, OCT4, and NANOG) were upregulated, while those related to apoptosis (Caspase 3) and autophagy (LC3B) showed a downward trend after supplementation with CHE. These results indicated that CHE improved the development of porcine embryos in vitro by reducing oxidative stress and autophagy levels.

The modulation of Nrf2 activity has been reported to be implicated in the pathology of various neurological disorders, including epilepsy. Previous studies have demonstrated that Nrf2 is activated in the post-status epilepticus rat model, however, the spatio-temporal, as well as cell type-specific expression of Nrf2 following brief epileptic seizures remains unclear. Here, we evaluated how an acute epileptic seizure affected the expression of Nrf2 and its downstream genes in the cortex and the hippocampus up to 1-week following the induced seizure. We found that after a pentylenetetrazol-induced seizure, Nrf2 significantly increased at 24 h at the mRNA level and 3 to 6 h at the protein level in the cortex. In the hippocampus, the Nrf2 mRNA level peaked at 3 h after the seizure, and no significant changes were observed in the protein level. Interestingly, the mRNA level of Nrf2 downstream genes peaked at 3-6 h after seizure in both the cortex and the hippocampus. A significant increase in the expression of Nrf2 was observed in the neuronal population of CA1 and CA3 regions of the hippocampus, as well as in the cortex. Moreover, we observed no change in the co-localization of Nrf2 with astrocytes neither in the cortex nor in CA1 and CA3. Our results revealed that following a brief acute epileptic seizure, the expression of Nrf2 and its downstream genes is transiently increased and peaked at early timepoints after seizure predominantly in the hippocampus, and this expression is restricted to the neuronal population.

Long Covid has many symptoms that overlap with ME(myalgic encephalomyelitis)/CFS(chronic fatigue syndrome), FM(fibromyalgia), EBV(Epstein-Barr virus), CMV(cytomegalovirus), CIRS (chronic inflammatory response syndrome), MCAS(mast cell activation syndrome), POTS(postural orthostatic tachycardia syndrome), and post viral fatigue syndrome. They all portend a “long haul” with an antioxidant shortfall and elevated Ca:Mg. Oxidative stress is the root cause. Linkage between TGF(transforming growth factor)-β, IFN(interferon)-γ, the RAS(renin angiotensin system), and the KKS(kallikrein kinin system) is discussed. Technical explanations for the renin aldosterone paradox in POTS, the betrayal of TGF-β, and the commonality of markers for the Warburg effect are offered. The etiology of the common Long Covid symptoms of post exertional malaise, fatigue, and brain fog as well as anosmia, hair loss, and GI symptoms is technically discussed. Ca:Mg is critical to the glutamate/GABA balance. The role of GABA and butyrates from the “good” intestinal bacteria in the gut-brain axis and its correlation with chronic fatigue diseases are explored. The crosstalk between the ENS(enteric nervous system) and the ANS(autonomic nervous system) and the role of the vagus in both are emphasized. HRV(heart rate variability), the fifth vital sign, points to an expanded gut-brain-heart/lung axis. A suggested approach to all of these - Long Covid, chronic fatigue diseases, post viral fatigue syndrome, and general health - is presented.

We conducted this study to determine the potential cryopreservative effects of different hesperidin (vitamin P; HSP) doses on ram semen after freeze-thawing. Semen samples were obtained from Sönmez rams by an artificial vagina. The samples were divided into six groups: control, 10, 50, 100, 250, and 500 µg/mL HSP (C, HSP10, HSP50, HSP100, HSP250, and HSP500, respectively). At the end of the study, sperm motility and kinetic parameters, plasma membrane acrosome integrity (PMAI), high mitochondrial membrane potential (HMMP), viability, lipid peroxidation levels (LPL), chromatin damage, oxidant parameters, and antioxidant parameters were assayed. None of the doses of HSP added to the semen extender showed any enhancing effect on progressive motility compared to C (p>0.05). In fact, HSP500 had negative effects (p<0.05). Moreover, PMI activities were the highest at the HSP10 dose, while LPL values were the lowest (p<0.05). The doses of HSP10 and HSP50 added to the Tris extender medium showed positive effects on spermatozoon chromatin damage. Consequently, we can say that HSP doses used in this study are not effective on semen progressive motility, but the HSP10 dose is effective on PMAI and chromatin damage by reducing LPL.

Silicon is an essential trace nutrient for plant growth and is frequently employed to remediate soils contaminated with heavy metals in agriculture. However, silicon’s role and mechanism in reducing heavy metal toxicity have not been well understood, especially for multi-heavy metals. In this study, the effects of silicon-rich materials (silicate, rice husk biochar (RHB), and bentonite) on growth trait, antioxidant response, and heavy metal accumulation and distribution of wheat grown in two soils polluted by multiple heavy metals (Cd, Zn, Pb, and As) were investigated. The results revealed that the addition of silicon-rich materials enhanced plant growth, improved the photosynthetic attributes in leaf tissues, and decreased the contents of Cd, Zn, Pb, and As in wheat shoots and grains. The examination of the subcellular distribution of heavy metals in plants implied that silicon-rich materials transferred heavy metals as intracellular soluble fractions to the cell walls, indicating the reduction of mobility and toxicity of heavy metals in the plants. In addition, the application of the silicon-rich materials reduced oxidative damage in plants by downregulating plant antioxidant response systems and decreasing the production of malondialdehyde (MDA), ascorbic acid (AsA), and glutathione (GSH). Moreover, fractionation analysis of soil heavy metals showed that silicon-rich amendments could convert bioavailable heavy metals into immobilized forms. The results indicated that silicon-rich materials could remediate multi-heavy metal-polluted soils and promote wheat production.

Contamination with Arsenic, a toxic metalloid, is increasing in the marine environment. Additionally, global warming can alter metalloids toxicity. Polychaetes are key species in marine environments. By mobilizing sediments, they play vital roles in nutrient and element (including contaminants) cycles. Most studies with marine invertebrates focused on the effects of metalloids on either adults or larvae. Here we bring information on the effects of temperature increase and arsenic contamination on the polychaete Hediste diversicolor in different growth stages and water temperatures. Feeding activity and biochemical responses – neurotransmission, indicators of cell damage, antioxidant and biotransformation enzymes and metabolic capacity - were evaluated. Temperature rise combined with As imposed alterations on feeding activity and biochemical endpoints at different growth stages. Small organisms have their antioxidant enzymes increased, avoiding lipid damage. However, larger organisms are the most affected class due to inhibition of superoxide dismutase, which resulted in protein damage. Oxidative damage was observed on smaller and larger organisms exposed to As and 21 °C, demonstrating higher sensibility to the combination of temperature rise and As. The observed alterations may have ecological consequences, affecting the cycle of nutrients, sediment oxygenation and the food chain that depend on the bioturbation of this polychaete.

Cells that experience high levels of oxidative stress respond with the induction of antioxidant proteins through the activation of the transcription factor Nrf2. Nrf2 is negatively regulated by Keap1 which binds to Nrf2 to facilitate its ubiquitination and ensuing proteasomal degradation under basal conditions. Here, we study protein folding and misfolding in Nrf2 and Keap1 in yeast, mammalian cells, and purified proteins under oxidative stress conditions. Both Nrf2 and Keap1 are susceptible to protein misfolding and inclusion formation upon oxidative stress. We propose that the intrinsically disordered regions within Nrf2 and the high cysteine content of Keap1 contribute to their oxidation and the ensuing misfolding. Our work reveals previously unexplored aspects of Nrf2 and Keap1 regulation and dysregulation by oxidation-induced protein misfolding.

Neuroprotective strategies for stroke remain inadequate. Nanoliposomes comprised of phos-phatidylcholine, cholesterol and monosialogangliosides (NL) induced an antioxidant protective response in endothelial cells exposed to amyloid insults. We tested the hypotheses that NL will preserve SH-SY5Y neuroblastoma cell viability following hypoxic injury and will reduce injury in mice following middle cerebral artery occlusion (MCAO). Neuroblastoma were exposed to 20-hour physoxic (5% oxygen) or hypoxic (1% oxygen) condition without or with NL (100 or 300 µg/mL). Viability was measured using calcein-AM fluorescence and SH-SY5Y gene expression of antioxidant proteins heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1) and superoxide dismutase 1 (SOD1) were measured by quantitative polymerase chain reaction. C57BL/6J mice were treated with saline (N=8) or NL (10000 ug/mL, N=7) while undergoing 60-minute MCAO followed by reperfusion. Day 2 post-injury neurologic impairment score and infarction size were compared. Neuroblastoma showed reduced viability following hypoxia that was reversed by NL. NL increased gene expression of HO-1, NQO1 and SOD1 versus controls. NL-treated mice showed reduced neurologic impairment and brain infarct size (18.8±2% versus 27.3±2.3%, p=0.017) versus controls. NL reduced stroke injury in mice subjected to MCAO likely through induction of an antioxidant stress response. NL is a candidate novel agent for stroke.

Introduction:In this study we evaluated the connivance of oxidative and antioxidative parameters in the pathogenesis of spinal cord injury (SCI). Although the etiology and pathogenesis of SCI remain to be fully understood, it has been suggested that reactive oxygen species (ROS) and oxidative stress may play a significant role in the pathophysiology of SCI. Furthermore, there is little information available in scientific literature about oxidative and antioxidative parameters in SCI patients. Methods:Oxidative stress was determined by measuring the levels of Lipid Peroxides (LPO) and Protein carbonyl in plasma and antioxidative parameters like Glutathione Reductase (GR), catalase and Glutathione peroxidase (GPx) in lysate in 40 SCI patients and 40 healthy subjects without SCI. However, pain was measured by McGill pain questionnaire. Results: Concentrations of catalase (p<0.01), GR (p<0.01) and GPx (p<0.01) were significantly lower in patients with SCI than in controls, and levels of oxidative stress parameters, LPO (p<0.01), Protein carbonyl (p<0.01) were significantly higher in patients than in controls. A significant positive correlation was found between LPO and pain score among SCI patients group. Furthermore, a significant positive correlation was also found between Protein carbonyl and pain score among SCI patients group than in control group. Conclusion: The present results indicate that SCI patients are exposed to oxidative stress and this escalated oxidative stress may play a role in the etiopathogenesis of the disease. Moreover, our results also show that increased oxidative stress parameters are more strongly amalgamated with pain in SCI patients.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rapidly increasing worldwide. A choline-deficient L-amino acid-defined high fat diet (CDHFD) has been used to create a mouse model of nonalcoholic steatohepatitis (NASH). There are some reports about the effects on mice of being fed CDAHFD for a long time, 1 to 3 months. However, the effect of this diet over a short period has been unknown. Therefore, we examined the effect of one week of feeding CDAHFD on the mouse liver. Feeding this diet for only one week induced lipid droplet deposition in the liver with increasing activity of liver-derived enzymes in the plasma. On the other hand, it did not induce fibrosis and cirrhosis. Additionally, it was demonstrated that mitochondrial respiration is significantly impaired with severe oxidative stress in the liver by CDAHFD, associated with a decreasing mitochondrial DNA copy number and complexes-proteins. In the gene expression analysis of the liver, inflammatory and oxidative stress markers were significantly increased by CDAHFD. These results demonstrated that one week of feeding CDAHFD to mice induces steatohepatitis with mitochondrial dysfunction and severe oxidative stress, without fibrosis, which can partially mimic the early stage of the NASH in humans.

Oxidative stress is an elevated intracellular level of free oxygen radicals that cause lipid peroxidation, protein denaturation, DNA hydroxylation, and apoptosis, ultimately negotiating cells viability. Antioxidants can scavenge such free radicals, thus reducing the oxidative stress and eventually prevent cellular damage. Medicinal plants, fruits, and spices remain the prioritized sources of antioxidants and antimicrobial properties since the time immemorial, but in contrast to plants, microorganisms can be grown at a faster rate under controlled conditions. They are non-toxic, non-carcinogenic, and biodegradable as compared to synthetic antioxidants. Microorganisms including actinomycetes, archaea, bacteria, protozoa, yeast, and fungi are auspicious source of vital bioactive compounds. The list comprises ample of bioactive components from microorganisms. One of them is bacteriocins, which are ribosomally synthesized antimicrobial peptides product of Eurotium sp., Streptomyces parvulus, S. thermophiles, Lactococcus lactis, etc. It has a great potential as next-generation antibiotics targeting the multiple-drug resistant pathogens. Pneumocandins are antifungal lipohexapeptides derived from the fungus Glarea lozoyensis, and inhibit 1,3-β-glucan synthase of the fungal cell wall and act as a precursor for the synthesis of caspofungin. It is widely used against invasive fungal infections and has been recently approved by the FDA. Taxol (paclitaxel), a chemotherapeutic drug derived from the bark of Taxus brevifolia can also be produced by endophytic fungi Taxomyces andreanae and Nodulisporium sylviforme. It is known to inhibit several fungi such as Pythium, Aphanomyces and Phytophthora. Hispidin and its derivate isolated from P. hispidus, reduce inducible nitric oxide synthase (iNOS) expression, obstruct the transcriptional activity of NF-κB, and also decrease the production of reactive oxygen species (ROS) in macrophages. Astaxanthin, known as an “aquatic” carotenoid produced by H. pluvialis, also has excellent ROS quenching activity. This study mainly focuses on fascinating antioxidant and antimicrobial compounds that have been scarcely investigated in microorganisms and discuss the promise and challenges of microorganisms as providers of health benefits.

Background: Post-operative delirium in elderly with hip fracture is associated with various adverse clinical outcomes. Nevertheless, the pathophysiological processes underpinning delirium have remained elusive. The aim of this study is to explore the associations between delirium and its features and immune-inflammatory and blood gas biomarkers.Methods: In this prospective study we examined 65 patients who underwent a hip fracture surgery and assessed the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), Richmond Agitation-Sedation Scale (RASS), and Delirium Rating Scale Revised-98 (DRS-R-98) before and during 4 days after the surgery. Complete Blood Count (CBC) and venous blood gas markers were obtained at the same time points.Results: Delirium was observed in 19 patients and was accompanied by significantly increased pO2, number of white blood cells, neutrophil percentage, and neutrophil/lymphocyte ratio, and lower mean platelet volume (MPV) (after adjusting for age, central nervous system (CNS) disease, blood loss during surgery, sleep disorders, and body mass index. The severity of delirium was associated with lowered number of platelets and MPV. Psychomotor disorders were associated with lower bicarbonate levels. The requirement of physical restraint of the patients was predicted by increased percentages of neutrophils and lymphocytes. Prior CNS disease was together with these biomarkers a significant predictor of delirium and severity of delirium. Conclusion: Delirium and psychomotor disorders following hip fracture and surgery may be caused by immune-inflammatory and oxidative stress pathways probably attributable to an aseptic inflammatory process. Oxygen administration may aggravate these pathways.

Metal exposure has been associated with a wide range of adverse birth outcomes and oxidative stress is a leading hypothesis of the mechanism of action of metal toxicity. We assessed the relationship between maternal exposure to essential and non-essential metals and metalloids in pregnancy and oxidative stress markers, and sought to identify windows of vulnerability and effect modification by fetal sex. In our analysis of 215 women from the PROTECT birth cohort study, we measured 14 essential and non-essential metals in urine samples at three time points during pregnancy. The oxidative stress marker 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite 2,3-dinor-5,6-dihydro-15-15-F2t-IsoP, as well as prostaglandin F2α (PGF2α), were also measured in the same urine samples. Using linear mixed models, we examined the main effects of metals on markers of oxidative stress as well as the visit-specific and fetal sex-specific effects. After adjustment for covariates, we found that a few urinary metal concentrations, most notably cesium (Cs) and copper (Cu), were associated with higher 8-iso-PGF2α with effect estimates ranging from 7.3 to 14.9 % for each interquartile range, increase in the metal concentration. The effect estimates were generally in the same direction at the three visits and a few were significant only among women carrying a male fetus. Our data show that higher urinary metal concentrations were associated with elevated biomarkers of oxidative stress. Our results also indicate a potential vulnerability of women carrying a male fetus.

Biomedical aspects of tattooing have been extensively discussed in literature, however pathophysiological effects of tattoo inks in the human body are still unexplored. Oxidative stress is considered responsible for the adverse effects of tattooing, however no experimental evidence for tattoo ink-related oxidative stress in the human body currently exists. The aim was to examine the effect of a blue tattoo on skin redox regulatory network (RRN) parameters in a single human subject. Skin surface oxidation-reduction potential (ORP) was analyzed with a PH60F flat probe. Interstitial and intracellular fluid enriched capillary blood from the tattoo and the control area was extracted and analyzed with I₂/KI-stabilized microORP, nitrocellulose redox permanganometry (NRP), carbonato-cobaltate (III) formation-derived H₂O₂ dissociation rate assay, 1,2,3-trihydroxybenzene autoxidation assay, thiobarbituric reactive substances (TBARS) assay and 5,5,’-dithio-bis-(2-nitrobenzoic acid) (DTNB)-based determination of free thiol content in low molecular weight and protein precipitate fractions. Surface ORP analysis revealed a greater antioxidant capacity of tattooed skin in comparison with the control (CTR). Capillary blood analysis confirmed greater reductive capacity in the tattoo sample both by microORP (-4.33mV vs CTR) and NRP (+10.8%). Hydrogen peroxide dissociation rate (+11.8%), and protein sulfhydryl content (+8.5%) were increased, and lipid peroxidation (-15%) was reduced in the tattoo sample in comparison with the CTR. In this N-of-1 study, RRN of tattooed skin was shifted towards a more reductive state with all parameters indicating reduced levels of oxidative stress in comparison with nontattooed skin. The local antioxidant effect of copper(II) phthalocyanine provides one possible explanation of the observed effects.

The immune system is a dynamic network of cells and cytokines are the major mediators of immune responses which combat pathogens. Based on the cytokine production, effector T cells differentiate into subsets known as Th1, Th2, Th17 or Treg (T regulatory). This system serves as a barrier to intracellular pathogens, bacterial infections and stimulates the production of reactive oxygen species (ROS), reactive nitrogen intermediates (RNI) and nitric oxide (NO), which diffuses across membranes and engulfs intracellular pathogens. Oxidative stress occurs when ROS, reactive nitrogen species (RNS) production and antioxidant defences become imbalanced. Oxidative stress generated by infected cells produces a substantial amount of free radicals which enables killing of intracellular pathogens. Intracellular pathogens are exposed to endogenous ROS as part of normal aerobic respiration, also aexogenous ROS and RNS are generated by the host immune system in response to infection. Nanoparticles which are designed for drug delivery are capable of trapping the desired drug in the particles which protects the drug from enzymatic degradation in a biological system. The small (subcellular) size of nanoparticles enables higher intracellular uptake of the drug which results in the reduction of the concentration of free drugs reducing their toxic effect. Research on the modulation of immune response and oxidative stress using nanoparticles used to encapsulate drugs has yet to be explored fully. In this review we illustrate the immune activation and generation of oxidative stress properties which are mediated by nanoparticle encapsulated drug delivery systems which can make the therapy more effective in case of diseases caused by intracellular pathogens.

Nitric oxide has been implicated in symptoms of ethanol withdrawal in animal models. Zebrafish have been used as models to study neurobehavioral effects of ethanol (EtOH) withdrawal, but the mechanisms associated with these effects are not yet clear. Adult zebrafish were treated with 1% EtOH for 20 min per day for 8 days, injected with the nitric oxide synthase 2 (NOS-2) inhibitor aminoguanidine (50 mg/kg), and allowed to experience withdrawal (WD) in their hometanks for 7 days. EtOH WD increased anxiety-like behavior in the novel tank test, an effect that was blocked by aminoguanidine. EtOH WD also increased brain levels of nitrite, an effect that was partially blocked by aminoguanidine. These results underline a novel mechanism by which NOS-2 controls anxiety-like responses to ethanol withdrawal, with implications for the mechanistic study of symptoms associated with chronic ethanol abuse.

Osteoarthritis (OA) is a disease that currently has no cure. There are numerous studies showing that carnosine and hyaluronic acid (HA) have a positive pharmacological action during joint inflammation. For this reason, the goal of this research was to discover the protective effect of a new HA+Carnosine formulation (FidHycarn) on the inflammatory response and on the cartilage degradation in in vivo experimental model of OA. This model was induced by a single intra-articular (i.ar.) injection of 25µl normal saline having 1mg of monosodium iodoacetate solution (MIA) in the knee joint. MIA injection caused histological alterations and degradation of cartilage as well as behavioral changes. Oral treatment with FidHycarn ameliorated the macroscopic signs, improved thermal hyperalgesia and weight distribution of hind paw as well as decreased histological and radiographic alterations. The oxidative damage was analyzed by evaluating the levels of nitrotyrosine and inducible nitric oxide synthase (iNOS) that were significantly reduced in FidHycarn rats. Moreover, the levels of pro-inflammatory cytokines and chemokines were also significantly reduced by FidHycarn. However, interestingly, in more cases, the effects of FidHycarn were not statistically different to Naproxen used as positive control. Thus, the new formulation containing Carnosine and HA could represent an interesting therapeutic strategy to combat osteoarthritis.

Chronic kidney disease (CKD) is a major non-communicable disease associated with high rates of premature morbidity and mortality. The prevalence of hypovitaminosis D (deficiency of 25(OH)D or 25D) is greater in racial/ethnic minorities and in patients with CKD than the general population. Low 25D is associated with bone and mineral disorders as well as immune, cardiometabolic and cardiovascular (CV) diseases. Thus, it has been suggested low 25D contributes to the poor outcomes in patients with CKD. The prevalence of hypovitaminosis D rises progressively with advancing severity of kidney disease with over 30% of patients with CKD stage 3 and 70% patients with CKD stage 5 estimated to have low levels of 25D. This report describes several of the abnormal physiologic and counter-regulatory actions related to low 25D in CKD such as those in oxidative stress and inflammatory systems, and some of the preclinical and clinical evidence or lack of thereof of normalizing serum 25D levels to improve outcomes in patients with CKD, and especially for the high risk subset of racial/ethnic minorities who suffer from higher rates of advanced CKD and hypovitaminosis D.

Huntington's disease (HD) is a progressive and fatal neurodegenerative disease caused by CAG repeat expansion in the coding region of huntingtin (HTT) protein. The accumulation of mutant HTT (mHTT) contributes to neurotoxicity by causing autophagy defects and oxidative stress that ultimately lead to neuronal death. Interestingly, epidemiologic studies have demonstrated that the prevalence of type-2 diabetes, a metabolic disease mainly caused by defective insulin signaling, is higher in patients with HD than in healthy controls. Although the precise mechanisms of mHTT-mediated toxicity remain unclear, the blockade of brain insulin signaling may initiate or exacerbate mHTT-induced neurodegeneration. In this study, we used an in vitro HD model to investigate whether neuronal insulin signaling is involved in mHTT-mediated neurotoxicity. Our results demonstrated that mHTT overexpression significantly impairs insulin signaling and causes apoptosis in neuronal cells. However, treatment with liraglutide, a GLP-1 analogue, markedly restores insulin sensitivity and enhances cell viability. This neuroprotective effect may be attributed to the contribution of the upregulated expression of genes associated with endogenous antioxidant pathways to oxidative stress reduction. In addition, liraglutide stimulates autophagy through AMPK activation, which attenuates the accumulation of HTT aggregates within neuronal cells. Our findings collectively suggest that liraglutide can rescue impaired insulin signaling caused by mHTT and that GLP-1 may potentially reduce mHTT-induced neurotoxicity in the pathogenesis of HD.

Neurodegenerative diseases like Alzheimer’s disease (AD) are poised to become a global health crisis, and therefore understanding the mechanisms underlying the pathogenesis is critical for the development of therapeutic strategies. Mutations in genes encoding presenilin occur in most familial Alzheimer’s disease but the role of PSEN in AD is not fully understood. In this review, the potential modes of pathogenesis of AD are discussed, focusing on calcium homeostasis and mitochondrial function. Moreover, research using Caenorhabditis elegans to explore the effects of calcium dysregulation due to presenilin mutations on mitochondrial function, oxidative stress and neurodegeneration is explored.

Accumulating evidence suggests that metformin, used as an antidiabetic drug, possesses anticancer properties. Metformin reduced the incidence and growth of experimental tumors in vivo. In a randomized clinical trial among nondiabetic patients, metformin treatment significantly decreased the number of aberrant crypt foci compared to the untreated group with a follow-up of 1 month. In our study, HT29 cells were treated with graded concentrations of metformin, 10 mM/25 mM/50 mM, for 24/48 hours. We performed immunofluorescence experiments by means of confocal microscopy and Western blot analysis to evaluate a panel of factors involved in apoptotic/autophagic processes and oxidative stress response. Moreover, HT29 cells treated with metformin were analyzed by flow cytometry assay to detect the cell apoptosis rate. The results demonstrate that metformin exerts growth inhibitory effects on cultured HT29 cells by increasing both apoptosis and autophagy; moreover, it affects the survival of cultured cells inhibiting the transcriptional activation of nuclear factor E2–related factor 2 (NRF-2) and nuclear factor–kappa B (NF-κB). The effects of metformin on HT29 cells were dose- and time-dependent. These results are very intriguing, since metformin is emerging as a multifaceted drug: it has a good safety profile and is associated with low cost, and it might be a promising candidate for the prevention or treatment of colorectal cancer.

Keywords: apoptosis; arbutus unedo L; formaldehyde; hippocampus; oxidative stress

Ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxide accumulation, plays a pivotal role in various pathological conditions, including neurodegenerative diseases. While reasonable evidence for ferroptosis exist e.g. in Parkinson’s disease or Alzheimer’s disease, there are only few reports on amyotrophic lateral sclerosis (ALS), a fast progressive and incurable neurodegenerative disorder characterized by progressive motor neuron degeneration. Initial studies, however, highlight that ferroptosis might be significantly involved in ALS. Key features of ferroptosis include oxidative stress, glutathione depletion, mitochondrial and dysfunction alterations in mitochondrial morphology, mediated by proteins such as GPX4, xCT, ACSL4 FSP1, Nrf2 and TfR1. Induction of ferroptosis involves small molecule compounds like erastin and RSL3, which disrupt system Xc- and GPX4 activity, respectively, yielding in lipid peroxidation and cellular demise. Mutations in Fused in Sarcoma (FUS) are associated with familial ALS. Pathophysiological hallmarks of FUS-ALS involve mitochondrial dysfunction and oxidative damage, implicating ferroptosis as putative cell death pathway in motor neuron demise. However, mechanistic understanding of ferroptosis in ALS, particularly FUS-ALS, remains limited. Here, we investigated ferroptosis vulnerability in a FUS-ALS cell model, revealing mitochondrial disturbance and increased susceptibility for ferroptosis in cells harboring the mutant FUS variant. This was accompanied by altered expression of ferroptosis-associated proteins, particularly by dramatic reduction of xCT expression, leading to cellular imbalance of the redox system and increased lipid peroxidation. Iron chelation with deferoxamine as well as inhibition of the mitochondrial calcium uniporter (MCU) significantly alleviated ferroptotic cell death and lipid peroxidation. These findings suggest a link between ferroptosis and FUS-ALS, offering potential therapeutic targets.

Acute HSV-1 infection is associated with mild symptom, such as fever and lesions of the mouth, face and skin. This phase is followed by a latency period before reactivation which is associated with symptoms ranging from ulcers to encephalitis. Despite available anti-HSV-1 drugs, the development of new antiviral agents is sought due to the presence of resistant viruses. Melatonin, a molecule secreted by the pineal gland, has been shown to be an antioxidant, inducer of antioxidant enzymes, and regulator of various biological processes. Clinical trials have explored its therapeutic utility in conditions including infections. This study focuses on melatonin's role in HSV-1 replication and the underlying mechanisms. Melatonin was found to decrease the synthesis of HSV-1 proteins in infected Vero cells measured by inmunofluorescence indicating an inhibition of HSV-1 replication. Additionally, it regulates the activities of antioxidant enzymes and affects proteasome activity. Melatonin activates the unfolded protein response (UPR) and autophagy and suppresses apoptosis in HSV-1-infected cells. In summary, melatonin demonstrates an inhibitory role in HSV-1 replication by modulating various cellular responses, suggesting its potential utility in the treatment of viral infections.

Phosphatase and tensin homolog (PTEN) is a tumor suppressor due to its ability to regulate cell survival, growth and proliferation by down-regulating PI3K/AKT signaling pathway. In addition, PTEN plays an essential role in other physiological events associated with cell growth demands, such as ischemia-reperfusion, nerve injury and immune response. Therefore, recently PTEN inhibition has emerged as a potential therapeutic intervention in these situations. Increasing evidence demonstrates that reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), are produced and required for the signaling in many important cellular processes under such physiological conditions. ROS have been shown to oxidize PTEN at the cysteine residue of its active site, consequently inhibiting its function. Here we provide an overview of studies that highlight the role of oxidative inhibition of PTEN in physiological processes.

In obesity, white adipose tissue expresses inflammatory cytokines leading to insulin resistance. Non-physiological meta-tyrosine and ortho-tyrosine (meta-Tyr and ortho-Tyr), produced from phenylalanine by free radicals, may contribute to the development of insulin resistance. The resulting insulin resistance may have a significant impact on macrophage function. In this study we aim to investigate microscopically the effect of meta- and ortho-Tyr on insulin sensitivity and M1/M2 polarization of macrophages using Akt phosphorylation and the arginase 1/iNOS ratio. Macrophage cell lines were cultured in media containing para-, meta- or ortho-Tyr, 5 mmol/L or 25 mmol/L glucose (para25-Tyr group) and treated with insulin. Para25, meta- and ortho-Tyr increased pAkt levels and decreased the arginase 1/iNOS ratio in macrophages in the absence of insulin. In the case of physiological para-tyrosine treatment, insulin increased the amount of pAkt and decreased the arginase 1/iNOS ratio. Both meta- and ortho-Tyr treatment were able to abolish or reverse the insulin’s increasing effect on pAkt and the decreasing effect on arginase 1/iNOS ratio. Our results suggest that non-physiological tyrosine isomers may affect the insulin signaling of macrophages and influence their M1/M2 polarization.

Diabetic retinopathy (DR) is a progressive blinding disease that affects vision and quality of life of patients and severely impacts society. This complication, caused by abnormal glucose metabolism, leads to structural, functional, molecular, and biochemical abnormalities in the retina. Oxidative stress (OS) and inflammation also play pivotal roles in the pathogenic process of DR, leading to mitochondrial damage and decrease in the mitochondrial function. DR causes retinal degeneration in glial and neural cells, while the disappearance of pericytes in retinal blood vessels leads to modifications in vascular regulation and stability. Clinical changes include dilatation and blood flow alterations in response to the reduce in retinal perfusion in retinal blood vessels, leading to vascular leakage, neovascularization and neurodegeneration. Thus, DR is a highly complex disease with various biological factors that contribute to its pathogenesis. The interplay between biochemical pathways and non-coding RNAs (ncRNAs) is essential for understanding the development and progression of DR. Abnormal expression of ncRNAs has been confirmed to promote the development of DR, suggesting that ncRNAs such as miRNAs, lnc-RNAs and circ-RNAs have potential as diagnostic biomarkers and theranostic targets in DR. This review provides an overview of interactions between abnormal biochemical pathways and dysregulated expression of ncRNAs under the influence of hyperglycemic environment in DR.

Breast cancer is a serious disease and the second leading cause of cancer-related death among women in the U.S. New treatments for this aggressive disease are urgently needed. Repurposing FDA-approved drugs for cancer treatment is an alternative that saves time and lowers the costs needed for drug development. In this study, we investigated the effects of proguanil, an anti-malarial drug, in breast cancer cells. Proguanil exhibited a significant cytotoxic effect on breast cancer cell lines including patient derived cell lines. Proguanil caused apoptosis through increased production of ROS and consequent decrease of mitochondrial membrane potential, mitochondrial respiration, and ATP production rates. ROS generation by proguanil was up to 3-fold higher when compared to the control. Proguanil treatment increased the expression of Bax, p-H2AX, cleaved-caspase 9, cleaved PARP, and down-regulated bcl-2 and survivin in breast cancer cell lines. The enlargement of 4T1 breast tumors in female Balb/c mice was suppressed by 55% through daily oral administration of 20mg/kg of proguanil. Western blot analyses of proguanil- treated tumors showed increased levels of p-H2AX, Bax, c-PARP, and c-caspase3 compared to control. Proguanil proved to be an efficient in vitro and in-vivo inhibitor of breast cancer cells, hence should be considered further for clinical investigation against breast cancer.

Oxidative stress is increasingly implicated in male secondary infertility, where the seminal plasma altered proteome composition plays a critical role. This study aims to explore proteomic changes in the seminal plasma of fertile individuals with oxidative stress and secondary infertility patients, hypothesizing oxidative stress as a key factor in secondary infertility. Pooled semen samples from both groups underwent quantitative proteomics analysis using advanced mass spectrometry, with subsequent bioinformatic analysis using tools like DAVID, STRING, and IPA for identifying differentially expressed proteins (DEPs). The study identified 377 DEPs in the secondary infertile group and 523 DEPs in healthy controls, revealing seven mutual pathways including acute phase response signaling and free radical scavenging. Significant alterations were noted in proteins like C3 and SERPINA3, associated with sperm function and fertility. The findings suggest that oxidative stress-induced proteomic alterations in seminal plasma are linked to secondary infertility, highlighting potential biomarkers and therapeutic targets. This research underscores the importance of understanding the interplay between oxidative stress and seminal plasma proteins, potentially guiding personalized treatment strategies to improve fertility outcomes in affected individuals.

Ferroptosis is a recent form of non-apoptotic cell death, which occurs due to imbalance of iron homeostasis (iron overload). Oxidative stress due to the impairment of the antioxidant system is a major pathophysiology during ferroptosis, which eventually results in lipid peroxidation. The cellular and physiological biomarker of ferroptotic cell death includes major alteration in the glutathione peroxidase 4 (GPX4) antioxidant system and lipid peroxidation induced loss of plasma membrane integrity. This review elaborates the mechanism of oxidative stress which triggers ferroptosis.

Consumption of high amounts of ethanol is a risk factor for development of cardiovascular diseases such as arterial hypertension. The hypertensive state induced by ethanol is a complex multi-factorial event, and oxidative stress is a pathophysiological hallmark of vascular dysfunction associated with ethanol consumption. Increasing levels of reactive oxygen species (ROS) in the vasculature triggers important processes underlying vascular injury, including accumulation of intracellular Ca2+ ions, reduced bioavailability of nitric oxide (NO), activation of mitogen-activated protein kinases (MAPKs), endothelial dysfunction, and loss of the anticontractile effect of perivascular adipose tissue (PVAT). The enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase plays a central role in vascular ROS generation in response to ethanol. Activation of the renin-angiotensin-aldosterone system (RAAS) is an upstream mechanism which contributes to NADPH oxidase stimulation, overproduction of ROS and vascular dysfunction. This review discusses the mechanisms of vascular dysfunction induced by ethanol, detailing the contribution of ROS to these processes. Data examining the association between neuroendocrine changes and vascular oxidative stress induced by ethanol are also reviewed and discussed. These issues are of paramount interest to public health as ethanol contributes to blood pressure elevation in the general population, and it is linked to cardiovascular conditions and diseases.

Atherogenic lipoproteins may impair vascular reactivity, leading to tissue damage in various organs, including the eye. This study aimed to investigate whether ophthalmic artery reactivity is affected in mice lacking the apolipoprotein E gene (ApoE-/-), a model for hypercholesterolemia and atherosclerosis. Twelve-month-old male ApoE-/- mice and age-matched wild-type controls were used to assess vascular reactivity using videomicroscopy. Moreover, vascular mechanics, lipid content, levels of reactive oxygen species (ROS), expression of pro-oxidant redox enzymes and of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) were determined in vascular tissue. Unlike the aorta, the ophthalmic artery of ApoE-/- mice developed no signs of endothelial dysfunction and no signs of excessive lipid deposition. Remarkably, levels of ROS, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), NOX2, NOX4, and of LOX-1 were increased in the aorta but not in the ophthalmic artery of ApoE-/- mice. Our findings suggest that ApoE-/- mice develop endothelial dysfunction in the aorta by increased oxidative stress via involvement of LOX-1, NOX1 and NOX2, whereas NOX4 may participate in media remodeling. In contrast, the ophthalmic artery appears to be resistant to chronic apolipoprotein E deficiency. Lack of LOX-1 expression/overexpression in response to increased ox-LDL levels may be a possible mechanism of action.

HMGB1 is a key late inflammatory mediator upregulated during air pollution-induced oxidative stress. Extracellular HMGB1 accumulation in the airways and lungs plays significant roles in the pathogenesis of inflammatory lung injury. Decreasing extracellular HMBG1 level may restore innate immune cell functions to protect the lungs from harmful injuries. Current therapies for air-pollution induced respiratory problems are inadequate. Dietary antioxidants from natural sources could serve as a frontline defense for air pollution-induced oxidative stress lung damage. Here, a standardized bioflavonoid antioxidant composition from Scutellaria baicalensis and Acacia catechu was evaluated for its efficacy in attenuating acute inflammatory lung injury and sepsis induced by oxidative stress and endotoxemia. Murine hyperoxia-exposed, bacterial-challenged acute lung injury, LPS-induced sepsis, and LPS-induced acute inflammatory lung injury models were utilized in vivo. Effect of the bioflavonoid composition on phagocytic activity and HMGB1 release was assessed using hyperoxia-stressed macrophages in vitro. Hematoxylin-eosin (HE) staining for lung tissue damage evaluation, ELISA for inflammatory cytokines and chemokines, western blot analysis for protein and HMGB1 as well as bacterial counts in the lung and airways have been performed. Statistically significant decrease in mortality (50%), reduced proinflammatory cytokines (TNF-α, IL-1β, IL-6) and chemokines (CINC-3) in serum and bronchoalveolar lavage, increased bacterial clearance of airways and lungs; reduced airway total protein, and extracellular HMGB1 were observed in vivo. A statistically significant 75.9% reduction in the level of HMGB1 and increased phagocytosis activity were also observed in vitro. The compilation of data in this report strongly suggest that the bioflavonoid composition could be indicated for oxidative stress induced lung damage protection possibly through attenuation of extracellular HMGB1.

The aim of this study was to assess the effects of three warm-up durations on post-exercise oxidative stress biomarkers, as well as recovery from the Wingate test in 14 amateur handball players. These players completed the Wingate test three times: after 5-min, after 10-min, and then after 15-min of warm-up, spread over two weeks with an interval of one week between each session. At the end of each session of the Wingate test, blood samples were taken: at rest (PR), after warming up (PWU) and immediately at the end of the test (P0), then after 10-min (P10) and after 20-min (P20) of recovery. The measured parameters are the total antioxidant status (TAS), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), malondialdehyde (MDA), protein-bound-carbonyls (PC) and thiobarbituric acid reactive substances (TBARS). The main findings revealed that anaerobic exercise induces oxidative stress, as evidenced by changes in antioxidant status and significant increases in concentrations of the majority of oxidative stress indicators (p < 0.05). At P20, plasma GPx, SOD, GR, TBARS, and PC contents, are lower and significantly different after a 15-min warm-up than after a 10-min or 5-min warm-up. ANOVA showed a significant ‘‘warm-up×recovery’’ effect on plasma GPx, SOD, GR, TBARS, and PC contents [F(8.104)=3.61; p<0.001; η2p=0.22, F(8.104): from 1.88 to 19.97; η2p: from 0.19 to 0.61: 0.05<p<0.001], respectively. We concluded that a 15-min warm-up was more efficient than the other duration in reducing free radical rise, emphasizing the importance of warm-up length on plasma oxidative stress biomarkers.

Porphyromonas gingivalis is a periodontopathogenic bacterium that can adhere and colonize periodontal tissues leading to inflammatory process, and consequently tissue destruction. New therapies using flavonoids such as hesperidin are being studied, and its promising properties have been highlighted. The aim of this study was to evaluate the effect of hesperidin on epithelial barrier function, reactive oxygen species (ROS) production and on inflammatory response caused by P. gingivalis in in vitro models. Integrity of the epithelial tight junctions challenged by P. gingivalis was determined by monitoring the transepithelial electrical resistance (TER). P. gingivalis adherence to a gingival keratinocyte monolayer and a basement membrane model were evaluated by a fluorescence assay. A fluorometric assay was used to determine the ROS production in gingival keratinocytes. The level of pro-inflammatory cytokines and matrix metalloproteinases (MMPs) secretion was evaluated by ELISA, while to assess NF-κB activation, the U937-3xjB-LUC monocyte cell line transfected with a luciferase reporter gene was used. Hesperidin protected against gingival epithelial barrier dysfunction caused by P. gingivalis and reduced the adherence of P. gingivalis to the basement membrane model. Hesperidin dose-dependently inhibited P. gingivalis-mediated ROS production by oral epithelial cells as well as the secretion of IL-1β, TNF- IL-8, MMP-2 and MMP-9 by macrophages challenged with P. gingivalis. Additionally, it was able to attenuate NF-κB activation in macrophages stimulated with P. gingivalis. These findings suggested that hesperidin has a protective effect on the epithelial barrier function, in addition to reduce ROS production and attenuate the inflammatory response associated with periodontal disease.