Renin Angiotensin System Blockage by Losartan Neutralize Hypercholesterolemia-Induced Inflammatory and Oxidative Injuries

Abstract Background: Hypercholesterolemia induces several metabolic diseases via oxidative and pro-inflammatory pathways. Renin angiotensin system (RAS) contributes to the pathogenesis of hypercholesterolemia-associated metabolic changes. Therefore, this study aims to explore the protective role of losartan (LT) against oxidative and inflammatory damages in different physiological systems including heart, liver and kidney tissues in hypercholesterolemic rats. Methods: After induction of hypercholesterolemia by high cholesterol diet for 6 weeks, LT was administered for 4 weeks. In serum samples, the levels of lipoproteins, aminotransferases, creatine kinases, urea, apoptosis and inflammatory markers were measured. In cardiac, hepatic and renal tissues, lipid peroxidation product and glutathione as well as antioxidant enzymatic activities were assayed. Finally, histopathological assessment evaluated the structural damage in in cardiac, hepatic and renal tissues. Results: Serum markers of cardiac, hepatic and renal toxicities including creatine kinases, aminotransferases and urea were attenuated by LT in hypercholesterolemic animals. Moreover, LT markedly corrected the elevated levels of lipoproteins, apoptosis and inflammatory biomarkers. Hypercholesterolemia-induced lipid peroxidation, low glutathione levels and diminished activities of antioxidant enzymes were prominently improved in LT treated animals. Histopathological alterations by hypercholesterolemia in heart, liver and kidney tissues were ameliorated by LT. Conclusion: This study confirmed the pathological enrolment of renin-angiotensin system in hypercholesterolemia-associated metabolic alterations. LT had a significant cardiac, hepatic and renal protective role against these impairments through down-regulation of oxidative damage, inflammation and necrosis.