BRIEF REPORT | doi:10.20944/preprints202207.0381.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Caspofungin; Candidemia; Cardiotoxicity; Troponin
Online: 26 July 2022 (03:43:51 CEST)
Echinocandins selectively inhibit fungal cell wall synthesis and, therefore, have few side effects. However, there are reports of hemodynamic and cardiac complications. We conducted this study to investigate the effects of caspofungin both on the noninvasive echocardiographic indices of myocardial function and on myocardial injury based on serum high-sensitivity cardiac troponin I (hs-cTnI) levels. This study was conducted on patients treated for candidemia. The hs-cTnI level and echocardiographic parameters were measured before and 1 hour after the infusion of the induction dose of caspofungin. Data were compared between central and peripheral venous drug administration routes. Fifteen patients were enrolled in the study. There were no significant differences in the echocardiographic parameters between the baseline and post-treatment period. The mean hs-cTnI level exhibited a significant rise following drug administration (0.24 ± 0.2 vs 0.32 ± 0.3; P = 0.006). There was also a significant difference concerning the hs-cTnI level between central and peripheral venous drug administration routes (P = 0.034). Due to differences in the hs-cTnI level, it appears that the administration of caspofungin may be associated with myocardial injury. Our findings also showed a higher possibility of cardiotoxicity via the central venous administration route.
REVIEW | doi:10.20944/preprints201612.0103.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: zebrafish; models; evaluation; drugs; cardiotoxicity; genotoxicity
Online: 20 December 2016 (10:34:56 CET)
Embryonic and larval Danio rerio is increasingly used as a toxicological model to conduct rapid in vivo tests and developmental toxicity assays; the zebrafish features as high genetic homology to mammals; robust phenotypes; and its value in high-throughput genetic and chemical screening have made it a powerful tool to evaluate in vivo toxicity. New methodologies of genome editing as CRISPR/Cas9; ZFN or Talen make it a suitable model to perform studies to pair human genetic diseases as well. This review surveys recent studies; employing zebrafish as experimental model; comparing it with other in vivo and in vitro models; presenting zebrafish as a potent vertebrate tool to evaluate drug toxicity to facilitate more extensive; easy and comprehensive knowledge of new generation drugs.
REVIEW | doi:10.20944/preprints201610.0028.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: mercury; antioxidants; cardiovascular diseases; cardiotoxicity; chelating agents
Online: 10 October 2016 (09:49:50 CEST)
Environmental contamination has exposed humans to various metal agents, including mercury. It has been determined that mercury is not only harmful to the health of vulnerable populations such as pregnant women and children, but is also toxic to ordinary adults in various ways. For many years, mercury was used in a wide variety of human activities. Nowadays, the exposure to this metal from both natural and artificial sources is significantly increasing. Recent studies suggest that chronic exposure, even to low concentration levels of mercury, can cause cardiovascular, reproductive and developmental toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, and carcinogenicity. Possible biological effects of mercury, including the relationship between mercury toxicity and diseases of the cardiovascular system, such as hypertension, coronary heart disease and myocardial infarction, are being studied. As heart rhythm and function are under autonomic nervous system control, it has been hypothesized that the neurotoxic effects of mercury might also impact cardiac autonomic function. Mercury exposure could have a long-lasting effect on cardiac parasympathetic activity and some evidence show that mercury exposure might affect heart rate variability, particularly early exposures in children. The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. The exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction and a reduction in the activity of antioxidant enzymes, such as glutathione peroxidase. In this review we report an overview on the toxicity of mercury and focus our attention on the toxic effects on the cardiovascular system.
REVIEW | doi:10.20944/preprints202304.0746.v2
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: cardiotoxicity, childhood cancer, chemotherapeutics agents, biomarkers, omics technology
Online: 24 April 2023 (04:06:08 CEST)
Improvements in the treatment of childhood cancer have considerably enhanced survival rates over the last decades, to over 80% as per today. However, this great achievement has been accompanied by the occurrence of several early and long-term treatment-related complications major of which is the cardiotoxicity. The chemotherapeutic agents that have been implicated as a cause of cardiotoxicity, are mostly anthracyclines and mitoxantrone, alkylating agents, proteasome inhibitors and to a lesser extent anti-microtubule agents, cisplatin, monoclonal antibodies, small molecular tyrosine kinase inhibitors, and nucleotide synthesis inhibitors. Routine diagnosis and monitoring of cardiotoxicity rely on electrocardiography and echocardiography. For the early detection of cardiotoxicity, in recent years, major studies have been conducted using biomarkers such as troponin, N-terminal pro b-natriuretic peptide, etc. Despite refinements in diagnostics still severe limitations exist, due to the increase of the above-mentioned biomarkers, only after significant cardiac damage has occurred. Lately, research has been expanded by introducing new technologies and finding new markers by omics approach. These new markers could be used not only for early detection, but also for early prevention of cardiotoxicity. The omics science, which includes genomics, transcriptomics, proteomics, and metabolomics, offers new opportunities for biomarker discovery in cardiotoxicity and may provide understanding of mechanisms of cardiotoxicity, beyond traditional technologies. This article reviews the contemporary definition of cardiotoxicity, older and newer chemotherapeutic agents mainly involved in cardiotoxicity and the methods of early and preventive diagnosis, using omics technology.
REVIEW | doi:10.20944/preprints202109.0104.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: hyrogel; cardiotoxicity; regenerative medicine; antineoplastic drugs; polydioxanone; pulmonary autograft
Online: 6 September 2021 (14:01:12 CEST)
Hydrogels, hydrophilic polymeric compounds, have been recently put under investigation as regenerative medicine applications and delivery systems for antineoplastic drugs, particularly chemotherapeutics (anthracyclines, alkylating agents), target drugs (trastuzumab) and immunotherapies. Porosity, conductivity, biodegradability and physical states are some of the peculiarities that render hydrogels suitable for therapies implementation. Chemically-modifying agents and enzymes can be also coupled to hydrogels for pharmacokinetical parameters improvement and side effects avoidance. Cardiotoxicity is in fact one of the major issues for oncological patients after treatment efficacy. Heart failure, myocarditis and hypertension are causes of morbidity and mortality that can possibly be avoided. Specific reaching of the target tumor site has been achieved by several authors in preclinical in vivo studies but clinical studies are currently under design processes. Polydioxanone, a hydrogel-mimicking agent, is capable to interact with the elastic properties of pulmonary artery. An advantageous characteristic is that can be also reabsorbed within biological systems and can cause a remodeling process of the vessel wall. Hydrogels currently represent a strong topic of interest for researchers and probably will guide future clinical investigations and practice.
ARTICLE | doi:10.20944/preprints201706.0017.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: evodiamine; primary cultured neonatal rat cardiomyocytes; zebrafish; cardiotoxicity; oxidative stress
Online: 2 June 2017 (08:07:04 CEST)
Evodiamine is a bioactive alkaloid that is specified as a biomarker for the quality assessment of Evodia rutaecarpa and for traditional Chinese medicines containing this plant. We previously reported that quantitative structure-activity modeling indicated that evodiamine may cause cardiotoxicity. However, previous investigations have indicated that evodiamine has beneficial effects in patients with cardiovascular diseases and there are no previous in vitro or in vivo reports of evodiamine-induced cardiotoxicity. The present study investigated the effects of evodiamine on primary cultured neonatal rat cardiomyocytes in vitro, and on zebrafish in vivo. Cell viability was reduced in vitro, where evodiamine had a 24-h 50% inhibitory concentration of 28.44 µg/mL. Cells exposed to evodiamine also showed increased lactate dehydrogenase release and maleic dialdehyde levels, and reduced superoxide dismutase activity. In vivo, evodiamine had a 10% lethal concentration of 354 ng/mL and induced cardiac malfunction, as evidenced by changes in heart rate and circulation, and pericardial malformations. This study indicated that evodiamine could cause cardiovascular side effects involving oxidative stress. These findings suggest that cardiac function should be monitored in patients receiving preparations containing evodiamine.
REVIEW | doi:10.20944/preprints202212.0354.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Anthracyclines; Cardiotoxicity; Heart failure; Chemotherapy toxicity; Cardio-Oncology; Breast cancer; Haematological cancer
Online: 20 December 2022 (04:26:21 CET)
Background: Anthracyclines form the backbone of many systemic chemotherapy regimens but dose-limiting cardiotoxicity can also lead to reduction in cardiac function and an increased risk of heart failure. Methods: This review was conducted in accordance with PRISMA guidelines and registered on PROSPERO (CRD42022373496). Results: 26 studies met the eligibility criteria including a total of 910 patients. Overall reduction in pooled mean left ventricular ejection fraction (LVEF) post‐anthracyclines in the placebo arms of included randomised-controlled trials was 4.6% (95% CI, 2.7 to 6.6). The trend in LVEF showed a progressive decline until approximately 180 days after which there was no significant change. Those receiving a cumulative anthracycline dose 300 mg/m2 experienced a more profound reduction. The risk of a 10% absolute decline in LVEF from baseline or decline to an LVEF below 50%, the overall pooled risk was 16% (95% CI: 11 to 21; I2 = 77%). Sensitivity analyses by baseline LVEF and trastuzumab treatment status did not yield significant differences. Conclusion: While the mean LVEF decline in patients without cardioprotective therapy was clinically small, a vulnerable subset experienced significant impairment. Further research to best identify those who benefit most from cardioprotective therapies when receiving anthracyclines are required.