Raunio H, Liira J, Elovaara E, Riihimäki V, Pelkonen O
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Toxicol Appl Pharmacol. 1990 Mar 15;103(1):175-9. doi: 10.1016/0041-008x(90)90273-w.
The rat hepatic cytochrome P450 induction pattern caused by administration of a high peroral dose of methyl ethyl ketone (MEK, 1.4 ml/kg once daily for 3 consecutive days) and m-xylene (1.0 ml/kg X 3) was studied by catalytic activity and immunoblotting techniques. MEK caused a marked increase in the amount of P450 isozymes belonging to the phenobarbital- and ethanol-inducible P450 subfamilies P450IIB and P450IIE, respectively. Catalytic activities linked with these isozymes, pentoxyresorufin O-depentylase (P450IIB), aniline hydroxylase, and N-nitrosodimethylamine N-demethylase (P450IIE), were also increased (18.0-, 5.4-, and 2.4-fold, respectively). The activity of ethoxyresorufin O-deethylase, which is predominantly linked with the polycyclic aromatic hydrocarbon-inducible P450 isozymes, was also increased 2.3-fold without an apparent increase in the amount of the respective P450 protein (P450IA). m-Xylene caused a similar induction pattern with less effect on P450IIE. Simultaneous administration of MEK and m-xylene resulted in an additive or, in the case of pentoxyresorufin O-depentylase, a potentiating effect on P450-linked catalytic activities. These data indicate that MEK and m-xylene elicit a qualitatively similar induction of P450 isozymes, which may play a role in the metabolic interactions of these compounds.
通过催化活性和免疫印迹技术研究了经口给予大鼠高剂量甲乙酮（MEK，1.4 ml/kg，每日一次，连续3天）和间二甲苯（1.0 ml/kg×3次）所引起的肝脏细胞色素P450诱导模式。MEK分别使属于苯巴比妥和乙醇诱导型P450亚家族P450IIB和P450IIE的P450同工酶量显著增加。与这些同工酶相关的催化活性，即戊氧基间苯二酚O - 脱戊基酶（P450IIB）、苯胺羟化酶和N - 亚硝基二甲胺N - 脱甲基酶（P450IIE）也增加了（分别为18.0倍、5.4倍和2.4倍）。主要与多环芳烃诱导型P450同工酶相关的乙氧基间苯二酚O - 脱乙基酶活性也增加了2.3倍，而相应的P450蛋白（P450IA）量没有明显增加。间二甲苯引起类似的诱导模式，但对P450IIE的影响较小。同时给予MEK和间二甲苯对P450相关的催化活性产生相加作用，对于戊氧基间苯二酚O - 脱戊基酶而言则产生增强作用。这些数据表明，MEK和间二甲苯在定性上对P450同工酶有相似的诱导作用，这可能在这些化合物的代谢相互作用中起作用。
