Mennes W C, Luijckx N B, Wortelboer H M, Noordhoek J, Blaauboer B J
Research Institute of Toxicology, University of Utrecht, The Netherlands.
Arch Toxicol. 1993;67(2):92-7. doi: 10.1007/BF01973677.
The hamster is known to display very high rates of monooxygenase-mediated biotransformation. In comparison with other species little knowledge has been gathered with respect to the nature of its cytochrome P450 enzymes and their respective inducibility. We studied the consequences of induction of P450 enzymes in rats and Syrian golden hamsters using the regioselective oxidative O-demethylation of the coumarin derivative scoparone. This metabolic conversion indicates differential effects of P450 inducers in the rat, in which various types of inducers cause different shifts in the isoscopoletin/scopoletin metabolite ratio (I/S-ratio). Liver microsomes from hamster not treated with P450 inducers oxidized scoparone much more efficiently than liver microsomes of untreated rats. In rat liver microsomes total demethylation rates of scoparone increased upon in vivo treatment with phenobarbital or beta-naphthoflavone. Phenobarbital reduced the I/S-ratio whereas beta-naphthoflavone caused an increase in this ratio. In hamster liver microsomes both phenobarbital and beta-naphthoflavone treatments resulted in a decrease in the I/S ratio. In this species the total scoparone demethylation rate was not much affected by phenobarbital, but beta-naphthoflavone caused a huge increase in over-all scoparone biotransformation. In both species, dexamethasone, isoniazid and clofibrate were much less effective. In contrast to the rat, in the hamster the scoparone biotransformation profile cannot be used to differentiate between phenobarbital- or beta-naphthoflavone-treated animals.
已知仓鼠表现出非常高的单加氧酶介导的生物转化速率。与其他物种相比，关于其细胞色素P450酶的性质及其各自的诱导性，人们了解得很少。我们使用香豆素衍生物滨蒿内酯的区域选择性氧化O-去甲基化研究了大鼠和叙利亚金仓鼠中P450酶诱导的后果。这种代谢转化表明P450诱导剂在大鼠中有不同的作用，其中各种类型的诱导剂会导致异滨蒿素/滨蒿素代谢物比率（I/S比率）发生不同的变化。未用P450诱导剂处理的仓鼠肝脏微粒体比未处理的大鼠肝脏微粒体更有效地氧化滨蒿内酯。在大鼠肝脏微粒体中，用苯巴比妥或β-萘黄酮进行体内处理后，滨蒿内酯的总去甲基化率增加。苯巴比妥降低了I/S比率，而β-萘黄酮导致该比率增加。在仓鼠肝脏微粒体中，苯巴比妥和β-萘黄酮处理均导致I/S比率降低。在该物种中，苯巴比妥对滨蒿内酯的总去甲基化率影响不大，但β-萘黄酮导致滨蒿内酯总体生物转化大幅增加。在这两个物种中，地塞米松、异烟肼和氯贝丁酯的效果要差得多。与大鼠不同，在仓鼠中，滨蒿内酯的生物转化谱不能用于区分苯巴比妥或β-萘黄酮处理的动物。
