The effects of cyclosporin on renal microsomal cytochrome P-450 systems

The effect of CsA on the renal microsomal cytochrome P-450 system was examined by using two animal models. Male Lewis rats and male white rabbits were treated with olive oil alone (Group A) or with CsA (30 mg/kg/day, Group B) by oral gavage for 7 and 14 days. Blood urea nitrogen and serum creatinine levels were determined at serial intervals after administration of CsA. In rats, BUN and S-Cr were increased, indicating the development of nephrotoxicity in group B by the 14th day after administration; BUN 78.8 mg/dl, S-Cr 3.2 mg/dl, but not in group A (BUN 29.3 mg/dl, S-Cr 0.7 mg/dl). In the rabbit experiments, BUN and S-Cr significantly increased in group B after 7 days of treatment but not in group A. P-450 content of the kidney microsomes prepared from rat and rabbit was examined. The renal specific P-450 content in group A was 68.8 pmol/mg protein in rats and 52.1 pmol/mg protein in rabbits, whereas those in group B showed 135.6 and 221.0 pmol/mg protein at day 14, respectively. SDS-PAGE also showed a significant increase in the content of P-450 after the CsA administration. Kidney microsomal aminopyrine N-demethylase activities were increased about 2.5 and 1.7 fold in rats and in rabbits, respectively. Monooxygenase activities for laurate and prostaglandin A1 were not significantly changed.(ABSTRACT TRUNCATED AT 250 WORDS)