Oral L-arginine protects against cyclosporine-induced hepatotoxicity in rats.
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: 7.5mg/kg/day; (4) L-Arg group: 2g/lt/day; (5) l-NAME (N-nitro-L-arginine methyl ester) group: 5mg/100ml/day; (6) CyA+L-Arg group: L-Arg (2g/lt/day)+CyA (7.5mg/kg/day); and (7) CyA+L-NAME group: CyA (7.5mg/kg/day)+L-NAME (5mg/100ml/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.
Kurus
Meltem
M
Department of Histology and Embryology, Faculty of Medicine, Inonu University, 44128 Malatya, Turkey. histomelita@yahoo.com
Esrefoglu
Mukaddes
M
Karabulut
Aysun Bay
AB
Sogutlu
Gokhan
G
Kaya
Mine
M
Otlu
Ali
A
D000284:Administration, Oral; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D016572:Cyclosporine / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007166:Immunosuppressive Agents / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008315:Malondialdehyde / Q000032:analysis; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D009569:Nitric Oxide; D008315:Malondialdehyde; D016572:Cyclosporine; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester