Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Effect of 5-Azacitine Treatment on Redox Status and Inflammatory Condition in MDS Patients

Version 1 : Received: 6 December 2021 / Approved: 8 December 2021 / Online: 8 December 2021 (14:36:28 CET)

A peer-reviewed article of this Preprint also exists.

Montes, P.; Guerra-Librero, A.; García, P.; Cornejo-Calvo, M.E.; López, M.S.; Haro, T.D.; Martínez-Ruiz, L.; Escames, G.; Acuña-Castroviejo, D. Effect of 5-Azacitidine Treatment on Redox Status and Inflammatory Condition in MDS Patients. Antioxidants 2022, 11, 139. Montes, P.; Guerra-Librero, A.; García, P.; Cornejo-Calvo, M.E.; López, M.S.; Haro, T.D.; Martínez-Ruiz, L.; Escames, G.; Acuña-Castroviejo, D. Effect of 5-Azacitidine Treatment on Redox Status and Inflammatory Condition in MDS Patients. Antioxidants 2022, 11, 139.

Journal reference: Antioxidants 2022, 11, 139
DOI: 10.3390/antiox11010139

Abstract

This study focused on the impact of the treatment with the hypomethylating agent 5-Azacitidine on the redox status and inflammation in 24 MDS patients. Clinical and genetic features of MDS patients were recorded and peripheral blood samples were used to determine the activity of the endogenous antioxidant defense system (superoxide dismutase, SOD, catalase, CAT, glutathion peroxidase, GPx, and reductase, GRd, activities), markers of oxidative damage (lipid peroxidation, LPO, and advanced oxidation protein products, AOPP). Moreover, pro-inflammatory cytokines and plasma nitrite plus nitrate levels as markers of inflammation, and CoQ10 plasma levels, were also measured. Globally, MDS patients showed less redox status in terms of a reduction in the GSSG/GSH ratio and in the LPO levels, and increased CAT activity compared with healthy subjects, with not changes in SOD, GPx and GRd activities, and AOPP levels. When analyzed the evolution from early- to advanced stages of the disease, the GPx activity, GSSG/GSH ratio, LPO and AOPP increased, with a reduction in CAT. GPx changes were related with the presence of risk factors such as high-risk IPSS-R or mutational score. Besides, there was an increase in IL-2, IL-6, IL-8 and TNF-α plasma levels, with further increase of IL-2 and IL-10 from early to advanced stage of the disease. However, we did not observe any association between inflammation and oxidative stress. Finally, 5-azacitidine treatment generates oxidative stress in MDS patients, without affecting inflammation levels, suggesting that oxidative status and inflammation are two independent processes.

Keywords

myelodysplastic syndrome (MDS); oxidative stress; cytokines; inflammation; 5-Azacitidine; somatic alterations

Subject

MEDICINE & PHARMACOLOGY, Oncology & Oncogenics

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