Siegers C P, Larseille J, Younes M
Res Commun Chem Pathol Pharmacol. 1982 Apr;36(1):61-73.
The effects of dithiocarb and (+)-catechin on the microsomal mixed-function oxidase system of rat liver were investigated after a single dose as well as after repeated treatment for 7 and for 28 days. Dithiocarb (200 mg/kg p.o.) significantly reduced the microsomal cytochrome P-450 content, aniline hydroxylase and aminopyrine demethylase activities; maximum decrease was observed at 4 hrs, return to normal values after 24 hrs. (+)-catechin (200 mg/kg p.o.) had no effects in this respect. Both agents did not affect microsomal enzyme activities when applied orally for 7 days. After 28 days treatment only dithiocarb (50 - 100 - 200 mg/kg p.o.) exerted a dose-dependent depression of the aniline hydroxylase activity. In vitro experiments confirmed the in vivo observations: a concentration-dependent inhibition of the aniline hydroxylation and aminopyrine demethylation were seen from the addition of dithiocarb, the I50-values were 5.4 X 10(-6) M and 9.6 X 10(-5) M, respectively. (+)-catechin showed no inhibitory activity on both enzyme activities in vitro. Both dithiocarb and (+)-catechin depressed the activity of the NADPH-cytochrome C-reductase only in the 10(-4) M concentration range, these effects should be therefore evaluated as non-physiological without relevance in vivo.
研究了二硫代氨基甲酸盐和(+)-儿茶素单次给药以及连续7天和28天重复给药后对大鼠肝脏微粒体混合功能氧化酶系统的影响。二硫代氨基甲酸盐(200mg/kg口服)显著降低了微粒体细胞色素P-450含量、苯胺羟化酶和氨基比林脱甲基酶活性;在4小时时观察到最大降幅,24小时后恢复到正常值。(+)-儿茶素(200mg/kg口服)在这方面没有影响。两种药物口服7天时均未影响微粒体酶活性。28天治疗后,只有二硫代氨基甲酸盐(50-100-200mg/kg口服)对苯胺羟化酶活性产生剂量依赖性抑制。体外实验证实了体内观察结果:加入二硫代氨基甲酸盐后可见对苯胺羟化和氨基比林脱甲基的浓度依赖性抑制,I50值分别为5.4×10(-6)M和9.6×10(-5)M。(+)-儿茶素在体外对两种酶活性均无抑制活性。二硫代氨基甲酸盐和(+)-儿茶素仅在10(-4)M浓度范围内降低NADPH-细胞色素C还原酶活性,因此这些作用应被视为非生理性的,在体内无相关性。