Swanson A B, Miller E C, Miller J A
Biochim Biophys Acta. 1981 Apr 3;673(4):504-16. doi: 10.1016/0304-4165(81)90482-7.
Safrole, estragole, and their 2',3'-oxides were hydroxylated by hepatic microsomes from rats and mice at the 1'-carbon; trans-anethole was hydroxylated at the 3'-carbon; and safrole, estragole, and their 1'-hydroxy derivatives were epoxidized at the 2',3'-double bond. The 2',3'-epoxidation of eugenol was just detectable. The formation of these metabolites was dependent on an NADPH-generating system and on cytochrome P-450. In the absence of 3,3,3-trichloropropylene oxide little or no safrole-, estragole-, or eugenol-2',3'-oxide was recovered when these oxides were added to the incubations; recoveries of 50-70% were obtained in its presence. The recoveries of the 2',3'-oxides of 1'-hydroxy-safrole and of 1'-hydroxyestragole were 50-80% in the absence of trichloropropylene oxide and nearly quantitative in its presence. All incubations for analysis of epoxidation rates contained trichloropropylene oxide. The rates of metabolite formation ranged from about 0.4 nmol of eugenol-2',3'-oxide/mg protein/h by female rat liver microsomes to about 270 nmol of trans-3'-hydroxyanethole/mg protein/h for male rat liver microsomes. The rates of epoxidation and hydroxylation were greater for the estragole derivatives than for the safrole derivatives. The rates of epoxidation of safrole and estragole were greater than for their 1'-hydroxy derivatives.
黄樟素、草蒿脑及其2',3'-氧化物在大鼠和小鼠的肝微粒体作用下于1'-碳位发生羟基化；反式茴香脑在3'-碳位发生羟基化；黄樟素、草蒿脑及其1'-羟基衍生物在2',3'-双键处发生环氧化。丁香酚的2',3'-环氧化仅可检测到。这些代谢产物的形成依赖于NADPH生成系统和细胞色素P-450。在不存在1,1,1-三氯环氧丙烷的情况下，当将这些氧化物添加到孵育体系中时，几乎没有或没有回收得到黄樟素、草蒿脑或丁香酚-2',3'-氧化物；在其存在时回收率为50 - 70%。在不存在三氯环氧丙烷的情况下，1'-羟基黄樟素和1'-羟基草蒿脑的2',3'-氧化物回收率为50 - 80%，在其存在时回收率接近定量。所有用于分析环氧化速率的孵育体系均含有三氯环氧丙烷。代谢产物形成速率范围从雌性大鼠肝微粒体每毫克蛋白每小时约0.4纳摩尔丁香酚-2',3'-氧化物到雄性大鼠肝微粒体每毫克蛋白每小时约270纳摩尔反式-3'-羟基茴香脑。草蒿脑衍生物的环氧化和羟基化速率高于黄樟素衍生物。黄樟素和草蒿脑的环氧化速率高于它们的1'-羟基衍生物。
