MODULATORY AND ANTIOXIDANT EFFECTS OF LIPOIC ACID ON CYCLOSPORINE A-INDUCED RENAL AND HEPATOTOXICITY IN MALE ALBINO RATS

Abstract

Cyclosporine A (CsA) is the most widely used immunosuppressive drug for preventing graft rejection and autoimmune disease. However, the therapeutic treatment induces several side effects such as nephrotoxicity, cardiotoxicity and hepatotoxicity. This study aimed to assess the protective role of lipoic acid (LA) on kidney and liver toxicity of male albino rats induced by cyclosporine (CsA). Forty adult male rats were allocated into four groups. Group (I) served as a control group. Group (II), received orally CsA (25 mg/kg b.w.), daily for 3 week. Group III (Recovery CsA group), treated orally with CsA (25 mg/kg b.w.), daily for 3 weeks, then recovered for other 3 weeks. Group IV (LA and CsA group), received LA (100 mg/kg b. w.) orally 1 h before treatment by CsA (25 mg/kg b. w.) daily for 3 weeks. The results indicated that treatment of CsA caused a significant elevation of serum urea, creatinine, uric acid and glucose. Also, a significant elevation of serum alanine and aspartate aminotransferases (ALT & AST), gamma glutamate transferase (GGT) activities was recorded in compared with control group. While, serum of total protein, albumin and globulin contents showed a highly significant decrease. Renal and hepatic malondialdehyde (MDA) concentration was markedly increased reflecting increased lipid peroxidation, whereas, reduced glutathione (GSH) and superoxide dismutase (SOD) were significantly decreased. On the other hand, LA plus CsA dose-dependently inhibited levels of serum urea, creatinine, uric acid, AST, ALT and GGT activity. Serum total protein, albumin, globulin and glucose restored in group (IV). The administration of LA plus CsA exhibited significant reduction of lipid peroxidation (LPO) while GSH content and SOD activity were enhanced significantly that reflecting improving renal and hepatotoxicity. In conclusion, the results demonstrate that lipoic acid has the potential to ameliorate cyclosporine A induced kidney and liver toxicity by improving lipid peroxidation, GSH content and restoring SOD activity.