Effect of cyclosporin on liver antioxidants and the protective role of vitamin E in hyperoxaluria in rats.
This study aimed to evaluate whether administration of cyclosporin to hyperoxaluric rats affects liver antioxidant status, and whether pretreatment with vitamin E reverses the effect. Male Wistar rats were divided into two major groups of 40. One group was given vitamin E. Both major groups were then divided into four subgroups which received vehicle (olive oil), cyclosporin in olive oil (50 mg kg(-1)), 3% ammonium oxalate or cyclosporin + 3% ammonium oxalate for three days. The activities of liver lactate dehydrogenase, glycolic acid oxidase and xanthine oxidase, and the level of malondialdehyde, an indicator of lipid peroxidation, increased when cyclosporin was administered to hyperoxaluric rats. The levels of antioxidants ascorbic acid, vitamin E and reduced glutathione and the activities of glutathione-metabolizing enzymes were altered significantly when hyperoxaluric rats were treated with cyclosporin. All these enzymes and antioxidants showed highly significant correlation values, r. These changes were restored to near normal by pretreatment with vitamin E. These findings suggest that cyclosporin-induced hepatotoxicity is aggravated in hyperoxaluria. This was almost totally prevented by pretreatment with vitamin E.
Adhirai
M
M
Department of Biochemistry, Dr A. L. M. PG Institute of Basic Medical Sciences, University of Madras, Taramani, India.
Selvam
R
R
D000818:Animals; D000975:Antioxidants / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000032:analysis; D016572:Cyclosporine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004347:Drug Interactions; D006959:Hyperoxaluria / Q000139:chemically induced / Q000503:physiopathology*; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D008111:Liver Function Tests; D008297:Male; D010070:Oxalates; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*
D000975:Antioxidants; D007166:Immunosuppressive Agents; D010070:Oxalates; D014810:Vitamin E; D016572:Cyclosporine; D001205:Ascorbic Acid