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.

An inverse association of weight and the occurrence of asymptomatic gallbladder stone disease in Hypercholesterolemia patients in northwest China: a case-control study.

“…The experimental observation revealed that signi cantly increased cholesterol loads lead to imbalances in the state of oxidation and reduction within tissues and ROS accumulation. excessive ROS can cause lipid peroxidation in cellular membranes, and eventually trigger cell death and tissue damage with the activation of transcription factors such as nuclear factor kappa B (NF-κB) and the generation of oxidized low-density lipoprotein [14,44]. Second, we found that serum LDL-c levels were signi cant positively associated with the risk of new-onset asymptomatic GSD in participants with hypercholesterolemia.…”

“…ischemic heart disease), fatty liver, and kidney disease since it might induce lipid peroxidation, low GSH levels, and diminished even after activities of antioxidant enzymes, and eventually cause functional damage to the endothelium, consequently morphological lesions develop. Note of, hypercholesterolemia, closely relating to diabetes and obesity, may deposit fats and triglycerides into the liver, which usually leads to cirrhosis of the liver or even cellular liver cancer [14,15]. In accordance with this viewpoint, another recent study showed that high levels of cholesterol were associated with gallbladder disorders such as cholesterolosis and gallstone disease, suggesting a positive association between hyperlipidemia and gallstones in humans [16].…”

“…Studies showed that a high cholesterol diet might trigger hypercholesterolemia even after short term exposure. In contrast, dietary factors that may prevent the development of gallstones include polyunsaturated fat, monounsaturated fat, ber, and caffeine [14]. In this study, we aimed to investigate the relationship between risk factors such as obesity and hypercholesterolemia with new-onset asymptomatic gallstone disease in a case-control study.…”

An Inverse Association of Weight and the Occurrence of Asymptomatic Gallbladder Stone Disease in Hypercholesterolemia Patients: A Case-control Study

“…The experimental observation revealed that signi cantly increased cholesterol loads lead to imbalances in the state of oxidation and reduction within tissues and ROS accumulation. Excessive ROS can cause lipid peroxidation in cellular membranes, and eventually trigger cell death and tissue damage with the activation of transcription factors such as nuclear factor kappa B (NF-κB) and the generation of oxidized low-density lipoprotein [14,44]. Second, the study showed that serum LDL-c levels were signi cant positively associated with the risk of new-onset asymptomatic GSD in participants with hypercholesterolemia.…”

“…Studies showed that a high cholesterol diet might trigger hypercholesterolemia even after short term exposure. In contrast, dietary factors that may prevent the development of gallstones include polyunsaturated fat, monounsaturated fat, ber, and caffeine [14]. This case-control study aimed to investigate the relationship between risk factors such as obesity and hypercholesterolemia with new-onset asymptomatic gallstone disease.…”