Effects of Candesartan and Losartan on Thioacetamide Induced Low Grade Renal Dysfunction in Rats

摘要

Background and Objective: Equivocal evidence exists concerning the role of angiotensin receptor blockers (ARBs) in renal injury, whether they are reno-protective or reno-toxic. Effect of low and high dose of losartan and candesartan (ARBs) was evaluated on murine model of low grade renal dysfunction. Materials and Methods: Low grade renal dysfunction was induced by thioacetamide 50 mg kg^?1 intraperitoneally once daily for two weeks. Rats were treated once daily by gastric gavage for 14 days as follows: Positive control (vehicle), two losartan (5 and 10 mg kg^?1) and two candesartan groups (0.1 and 0.3 mg kg^?1) and normal control group. At end of treatment, blood urea and creatinine were measured in addition to the histopathological examination of renal tissues. Results: Only losartan 10 mg kg^?1 revealed significant decrease in blood urea and creatinine compared to the positive control group. Thioacetamide caused a decrease in glomerular cellularity, widening of capsular space and dilatation of tubular lumina with desquamation of epithelium. Only losartan 10 mg kg^?1 reversed these changes. Conclusion: A high dose of losartan protects against low grade renal dysfunction in rats. Larger studies are recommended to further elucidate the underlying mechanisms.