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)
Yoshimura
R
R
Department of Urology, Osaka City University Medical School, Japan.
Yoshimura
N
N
Nakatani
T
T
Kusunose
E
E
Yamaguchi
T
T
Oka
T
T
Kishimoto
T
T
D000818:Animals; D015153:Blotting, Western; D016572:Cyclosporine / Q000009:adverse effects / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew
D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System