Yoshimura R, Yoshimura N, Nakatani T, Kusunose E, Yamaguchi T, Oka T, Kishimoto T
Department of Urology, Osaka City University Medical School, Japan.
Clin Nephrol. 1993 Dec;40(6):339-45.
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)
通过使用两种动物模型研究了环孢素A（CsA）对肾微粒体细胞色素P - 450系统的影响。雄性Lewis大鼠和雄性白兔分别单独用橄榄油灌胃（A组）或用CsA（30 mg/kg/天，B组）灌胃7天和14天。在给予CsA后按一定时间间隔测定血尿素氮和血清肌酐水平。在大鼠中，BUN和S - Cr升高，表明给药后第14天B组出现肾毒性；BUN为78.8 mg/dl，S - Cr为3.2 mg/dl，而A组未出现（BUN为29.3 mg/dl，S - Cr为0.7 mg/dl）。在兔实验中，治疗7天后B组的BUN和S - Cr显著升高，而A组未升高。检测了从大鼠和兔制备的肾微粒体的P - 450含量。A组大鼠肾特异性P - 450含量为68.8 pmol/mg蛋白，兔为52.1 pmol/mg蛋白，而B组在第14天分别为135.6和221.0 pmol/mg蛋白。SDS - PAGE也显示给予CsA后P - 450含量显著增加。大鼠和兔肾微粒体氨基比林N - 脱甲基酶活性分别增加约2.5倍和1.7倍。月桂酸和前列腺素A1的单加氧酶活性无显著变化。（摘要截短至250字）
