Oral l-arginine protects against cyclosporine-induced hepatotoxicity in rats

Abstract

Cyclosporine A (CyA) leads to liver injury, probably by causing the production of free radicals and resulting in nitric oxide (NO) deficiency. We evaluated CyA-mediated liver damage histopathologically to determine the possible beneficial effects of l-arginine ( l-Arg). In this study, 7 groups of Sprague–Dawley rats; (1) Control group; (2) 0.9% NaCl group; (3) CyA group: 7.5 mg/kg/day; (4) l-Arg group: 2 g/lt/day; (5) l-NAME ( N-nitro- l-arginine methyl ester) group: 5 mg/100 ml/day; (6) CyA+ l-Arg group: l-Arg (2 g/lt/day)+CyA (7.5 mg/kg/day); and (7) CyA+ l-NAME group: CyA (7.5 mg/kg/day)+ l-NAME (5 mg/100 ml/day) were included. At the end of the treatments, animals were killed and hepatic tissues were treated for morphological (hematoxylin and eosin) and biochemical (NO and malondialdehyde, MDA) analyses, and serum was processed for biochemical (alanine transaminase (ALT), aspartate transaminase (AST), bilirubin, alkaline phosphatase (ALP) and total protein) study. The results indicated that CyA-induced hepatotoxicity was characterized by sinusoidal dilatation, hepatocellular vacuolization, neutrophilic infiltration and hepatocellular necrosis. These findings were less pronounced in the CyA+ l-Arg group than CyA alone group. l-NAME group showed moderate changes. The CyA+ l-NAME (Group 7) had more severe changes. We found changes in tissue NO and MDA levels. We think that the tissue damage caused by CyA is mild and reversible at the period when biochemical parameters are just starting to become abnormal and that l-Arg may have a protective effect against CyA damage on liver.