Luo G, Guenthner T M
Department of Pharmacology, College of Medicine, University of Illinois at Chicago.
J Pharmacol Exp Ther. 1995 Feb;272(2):588-96.
The metabolism of allylbenzene 2',3'-oxide, estragole 2',3'-oxide, allylbenzene and estragole was studied in the isolated perfused rat liver. Formation of dihydrodiol and glutathione conjugate metabolites was detected for both epoxides and the presence of dihydrodiol metabolites after perfusion of allylbenzene or estragole indicated the formation of allylic epoxide intermediates in the intact liver. A comparison of elimination kinetics for parent compounds and epoxides indicated that epoxides were relatively rapidly detoxified and probably do not accumulate on formation in vivo. Acute toxicity of epoxides, measured as the release of alanine aminotransferase activity into the perfusate, or genetic toxicity, determined as covalent binding of radiolabeled epoxide to DNA, were not observed. It was concluded that both epoxide hydrolases and glutathione S-transferases can effectively detoxify the allylic epoxides derived from either allylbenzene or estragole and effectively prevent cellular or genetic toxicity of these reactive intermediates. Epoxide hydrolases appear to play the major role in the detoxication of these epoxides in vivo.
在离体灌注大鼠肝脏中研究了烯丙基苯2',3'-氧化物、草蒿脑2',3'-氧化物、烯丙基苯和草蒿脑的代谢。两种环氧化物均检测到二氢二醇和谷胱甘肽共轭代谢物的形成，并且在灌注烯丙基苯或草蒿脑后存在二氢二醇代谢物，这表明在完整肝脏中形成了烯丙基环氧化物中间体。母体化合物和环氧化物消除动力学的比较表明，环氧化物相对迅速地被解毒，并且在体内形成时可能不会积累。未观察到以丙氨酸转氨酶活性释放到灌注液中衡量的环氧化物急性毒性，或作为放射性标记环氧化物与DNA共价结合测定的遗传毒性。得出的结论是，环氧化物水解酶和谷胱甘肽S-转移酶都可以有效地解毒源自烯丙基苯或草蒿脑的烯丙基环氧化物，并有效预防这些反应性中间体的细胞毒性或遗传毒性。环氧化物水解酶似乎在体内这些环氧化物的解毒中起主要作用。
