Mennes W C, van Holsteijn C W, Timmerman A, Noordhoek J, Blaauboer B J
Research Institute of Toxicology, University of Utrecht, The Netherlands.
Biochem Pharmacol. 1991 Apr 15;41(8):1203-8. doi: 10.1016/0006-2952(91)90659-s.
The coumarin derivative scoparone is regioselectively demethylated yielding isoscopoletin and scopoletin. The ratio of the formation rates of these two metabolites (isoscopoletin/scopoletin; I/S ratio) is reported to mirror the contribution of several cytochrome P450 (P450) isoenzymes to the biotransformation of scoparine. The metabolism of scoparine has been studied in primary liver cell cultures of rats, hamsters, cynomolgus monkeys and in human liver cells. Rat hepatocytes appeared to metabolize scoparone 7 to 10 times slower than those of hamsters and monkeys. In hepatocyte monolayers of all three species the loss of P450 was paralleled by a decrease in total scoparone metabolism. In hamsters but not in rats, a decrease of the I/S ratio was found during primary culture of liver cells. A similar shift in the metabolic pattern of scoparine observed with the monkey hepatocytes was statistically not significant. Most likely, in hamster and possibly in monkey hepatocyte cultures the different P450s involved in scoparone metabolism decrease at unequal rates. In rat liver cells, however, the pattern of these P450 isoenzymes remains more or less unaltered. In contrast to liver cells from the other species, human hepatocytes did not secrete scopoletin in detectable amounts. Scoparone demethylation in humans may be qualitatively different from that in other mammals.
香豆素衍生物滨蒿内酯被区域选择性去甲基化，生成异滨蒿素和滨蒿素。据报道，这两种代谢产物的生成速率之比（异滨蒿素/滨蒿素；I/S比）反映了几种细胞色素P450（P450）同工酶对滨蒿素生物转化的贡献。已在大鼠、仓鼠、食蟹猴的原代肝细胞培养物以及人肝细胞中研究了滨蒿素的代谢。大鼠肝细胞代谢滨蒿内酯的速度似乎比仓鼠和猴子的肝细胞慢7至10倍。在所有这三个物种的肝细胞单层中，P450的损失与滨蒿内酯总代谢的减少同时出现。在仓鼠而非大鼠中，在肝细胞原代培养过程中发现I/S比降低。在猴子肝细胞中观察到的滨蒿素代谢模式的类似变化在统计学上不显著。很可能，在仓鼠以及可能在猴子肝细胞培养物中，参与滨蒿内酯代谢的不同P450以不同的速率减少。然而，在大鼠肝细胞中，这些P450同工酶的模式或多或少保持不变。与其他物种的肝细胞不同，人肝细胞未分泌可检测量的滨蒿素。人肝脏中滨蒿内酯的去甲基化在性质上可能与其他哺乳动物不同。
