Effect of 5-Azacitidine Treatment on Redox Status and Inflammatory Condition in MDS Patients Montes, Paola Guerra Librero Rite, Ana García Martín, Paloma Cornejo Calvo, María Elena López Vélez, María del Señor Haro Muñoz, Tomás de Martínez Ruiz, Laura Escames Rosa, Germaine Acuña Castroviejo, Darío Myelodysplastic syndrome (MDS) Oxidative stress Cytokines Inflammation 5-azacitidine Somatic alterations This study was partially supported by grants from the Instituto de Salud Carlos III through the project CB/10/00238 (co-funded by European Regional Development Fund/European Social Fund “Investing in your future”); the Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (CTS-101), Spain; and the UGC de Laboratorios Clínicos, Hospital Universitario San Cecilio, Granada, Spain. 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, as well as 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, as well as increased CAT activity compared with healthy subjects, with no changes in SOD, GPx, and GRd activities, or AOPP levels. When analyzing the evolution from early to advanced stages of the disease, we found that the GPx activity, GSSG/GSH ratio, LPO, and AOPP increased, with a reduction in CAT. GPx changes were related to the presence of risk factors such as high-risk IPSS-R or mutational score. Moreover, there was an increase in IL-2, IL-6, IL-8, and TNF- plasma levels, with a further increase of IL-2 and IL-10 from early to advanced stages of the disease. However, we did not observe any association between inflammation and oxidative stress. Finally, 5-azacitidine treatment generated oxidative stress in MDS patients, without affecting inflammation levels, suggesting that oxidative status and inflammation are two independent processes. 2022-02-14T11:13:37Z 2022-02-14T11:13:37Z 2022-01-09 journal article Montes, P... [et al.]. Effect of 5-Azacitidine Treatment on Redox Status and Inflammatory Condition in MDS Patients. Antioxidants 2022, 11, 139. [https://doi.org/10.3390/antiox11010139] http://hdl.handle.net/10481/72825 10.3390/antiox11010139 eng http://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España MDPI