Bani M H, Fukuhara M, Kimura M, Ushio F
Department of Pharmaceutical Sciences, National Institute of Public Health, Minato-ku, Tokyo, Japan.
Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1998 Feb;119(2):143-8. doi: 10.1016/s0742-8413(97)00201-6.
Induction mode of the hepatic drug-metabolizing enzymes was studied in Corn snake (Elaphe guttata emoryi). Treatment of snakes with 3-methylcholanthrene or phenobarbital produced no effects on liver weight and total content of cytochromes P450 and b5. Treatment with 3-methylcholanthrene significantly induced the activities of arylhydrocarbon hydroxylase, 7-ethoxyresorufin O-deethylase and 7-pentoxyresorufin O-dealkylase, whereas those of ethoxycoumarin O-deethylase, benzphetamine N-demethylase, erythromycin N-demethylase and testosterone hydroxylases were not affected. 3-Methylcholanthrene-induced activities of 7-ethoxyresorufin O-deethylase and 7-pentoxyresorufin O-dealkylase were inhibited by 20 microM alpha-naphthoflavone by 98% and 73%, respectively. Phenobarbital-treatment caused a significant induction of the activities of erythromycin N-demethylase and testosterone 6 beta-hydroxylase, but did not affect those of the other phase I enzymes and the other testosterone hydroxylases. The activities of UDP-glucuronyltransferase and glutathione S-transferase were not affected by either 3-methylcholanthrene or phenobarbital administration. Immunoblotting showed that 3-methylcholanthrene-treatment induced a protein band related to hamster CYP1A2, and decreased the intensity of the two bands detected with anti-rat CYP2B1. Phenobarbital-treatment did not affect the intensity of CYP2B-related proteins. The results suggest that snake liver has multiple forms of cytochrome P450, notably those inducible by 3-methylcholanthrene.
在玉米锦蛇（Elaphe guttata emoryi）中研究了肝脏药物代谢酶的诱导模式。用3-甲基胆蒽或苯巴比妥处理蛇对肝脏重量以及细胞色素P450和b5的总含量没有影响。用3-甲基胆蒽处理显著诱导了芳烃羟化酶、7-乙氧基试卤灵O-脱乙基酶和7-戊氧基试卤灵O-脱烷基酶的活性，而乙氧基香豆素O-脱乙基酶、苄非他明N-脱甲基酶、红霉素N-脱甲基酶和睾酮羟化酶的活性未受影响。20微摩尔的α-萘黄酮分别抑制了3-甲基胆蒽诱导的7-乙氧基试卤灵O-脱乙基酶和7-戊氧基试卤灵O-脱烷基酶活性的98%和73%。苯巴比妥处理显著诱导了红霉素N-脱甲基酶和睾酮6β-羟化酶的活性，但不影响其他I相酶和其他睾酮羟化酶的活性。UDP-葡萄糖醛酸基转移酶和谷胱甘肽S-转移酶的活性不受3-甲基胆蒽或苯巴比妥给药的影响。免疫印迹显示，3-甲基胆蒽处理诱导出一条与仓鼠CYP1A2相关的蛋白条带，并降低了用抗大鼠CYP2B1检测到的两条条带的强度。苯巴比妥处理不影响CYP2B相关蛋白的强度。结果表明，蛇肝脏有多种形式的细胞色素P450，尤其是那些可被3-甲基胆蒽诱导的形式。
