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We aimed to determine the effects of evolocumab on the plasma lipid profile, reactive oxygen species (ROS), and nitric oxide (NO) generation in the heart of adult male obese Zucker rats. Methods: The rats were divided into lean and obese controls and obese rats treated with evolocumab subcutaneously at a dose of 10 mg\/kg every two weeks. After 6 weeks, the lipid profile was determined in the plasma, and NO synthase (NOS) activity, thiobarbituric acid reactive substance (TBARS), conjugated diene (CD) concentration, and protein expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, nuclear factor kappaB (NF-\u03baB), endothelial NOS (eNOS), and phosphorylated eNOS (peNOS) were measured in the heart. Results: Evolocumab treatment did not reduce body weight, relative heart weight, or systolic blood pressure in obese Zucker rats. Evolocumab treatment, however, reduced plasma LDL levels, TBARS, and CD concentrations along with decreasing expression of NADPH oxidase and NF-kappaB proteins in the heart. On the other hand, evolocumab had no effect on NOS activity or eNOS and peNOS protein expression. Conclusions: Besides its lipid-lowering effect, evolocumab may exert antioxidant properties and protect cardiomyocytes from lipid peroxidation while not affecting NO production.<\/jats:p>","DOI":"10.3390\/pathophysiology32010005","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T05:47:42Z","timestamp":1737438462000},"page":"5","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evolocumab Reduces Oxidative Stress and Lipid Peroxidation in Obese Zucker Rats"],"prefix":"10.3390","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0132-670X","authenticated-orcid":false,"given":"Martina","family":"Cebova","sequence":"first","affiliation":[{"name":"Institute of Normal and Pathological Physiology, Center of Experimental Medicine, Slovak Academy of Sciences, 813 71 Bratislava, Slovakia"},{"name":"Institute of Pathophysiology, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radoslava","family":"Bulkova","sequence":"additional","affiliation":[{"name":"Institute of Normal and Pathological Physiology, Center of Experimental Medicine, Slovak Academy of Sciences, 813 71 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5476-2949","authenticated-orcid":false,"given":"Olga","family":"Pechanova","sequence":"additional","affiliation":[{"name":"Institute of Normal and Pathological Physiology, Center of Experimental Medicine, Slovak Academy of Sciences, 813 71 Bratislava, Slovakia"},{"name":"Institute of Pathophysiology, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gaggini, M., Gorini, F., and Vassalle, C. 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