Ishikawa M, Sasaki K, Ozaki M, Watanabe K, Takayanagi Y, Sasaki K
Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku College of Pharmacy, Sendai, Japan.
J Pharmacobiodyn. 1991 Mar;14(3):132-8. doi: 10.1248/bpb1978.14.132.
Effect of carrageenan-induced inflammation on hepatic drug metabolism was studied in male and female Wistar rats. One day after treatment of male and female Wistar rats with carrageenan (1%, 0.1 ml, s.c.) (i) a prolongation of the duration of sleeping time induced by hexobarbital (100 mg/kg, i.p.), (ii) decreases biotransformation of hexobarbital, aminopyrine and ethylmorphine in the hepatic 9000 x g supernatants (S-9) and (iii) a decrease in cytochrome P-450 content were observed in males but not female rats. However, carrageenan treatment did not alter aniline hydroxylase activity in animals of either sex. Carrageenan also suppressed induction of hexobarbital, aminopyrine and ethylmorphine metabolism by phenobarbital treatment, and depressed the induction of hepatic S-9 cytochrome P-450 content caused by phenobarbital treatment. These data show that there is a sex-related difference in the ability of carrageenan to alter hepatic drug metabolism, which is substrate-specific, in the rats.
在雄性和雌性Wistar大鼠中研究了角叉菜胶诱导的炎症对肝脏药物代谢的影响。在用角叉菜胶(1%,0.1 ml,皮下注射)处理雄性和雌性Wistar大鼠一天后,在雄性大鼠中观察到:(i)己巴比妥(100 mg/kg,腹腔注射)诱导的睡眠时间延长;(ii)肝脏9000×g上清液(S-9)中己巴比妥、氨基比林和乙基吗啡的生物转化减少;(iii)细胞色素P-450含量降低,但在雌性大鼠中未观察到这些现象。然而,角叉菜胶处理并未改变任一性别动物的苯胺羟化酶活性。角叉菜胶还抑制了苯巴比妥处理对己巴比妥、氨基比林和乙基吗啡代谢的诱导作用,并降低了苯巴比妥处理引起的肝脏S-9细胞色素P-450含量的诱导。这些数据表明,在大鼠中,角叉菜胶改变肝脏药物代谢的能力存在性别相关差异,且这种差异具有底物特异性。