Osimitz T G, Kulkarni A P
Drug Metab Dispos. 1985 Mar-Apr;13(2):197-203.
The effects of in vitro addition of polyamines on the female mouse hepatic microsomal cytochrome P-450- and flavin-containing monooxygenase-dependent oxidation of xenobiotics were examined. Putrescine, spermine, and spermidine all caused a different degree of stimulation of oxidative dearylation of parathion and O-ethyl-O-p-nitrophenylphosphonothioate, epoxidation of aldrin, and O-deethylation of 7-ethoxycoumarin. The degree of stimulation was greatest in the presence of spermidine. Enhancement of aldrin epoxidation by spermidine was higher in pregnant mice as compared to nonpregnant mice. Total phorate S-oxidation was stimulated by all the polyamines tested. Phorate S-oxidation, mediated by microsomal flavin-containing monooxygenase, was only slightly increased by spermine and spermidine while putrescine caused slight inhibition. Of the various steps involved in the monooxygenation cycle examined, only the rates of NADPH oxidation and cytochrome P-450 reduction were significantly increased. Efficient coupling of NADPH utilization with substrate oxidation appears to be the underlying mechanism responsible for the polyamine-stimulated xenobiotic oxidation.
研究了体外添加多胺对雌性小鼠肝微粒体细胞色素P - 450和含黄素单加氧酶依赖的外源化合物氧化的影响。腐胺、精胺和亚精胺均对硫磷和O - 乙基 - O - 对硝基苯基硫代磷酸酯的氧化脱芳基作用、艾氏剂的环氧化作用以及7 - 乙氧基香豆素的O - 去乙基化作用产生不同程度的刺激。在亚精胺存在的情况下刺激程度最大。与未怀孕小鼠相比，亚精胺对怀孕小鼠艾氏剂环氧化的增强作用更高。所有测试的多胺均刺激了甲拌磷的总S - 氧化作用。由微粒体含黄素单加氧酶介导的甲拌磷S - 氧化作用，精胺和亚精胺使其仅略有增加，而腐胺则导致轻微抑制。在所研究的单加氧循环的各个步骤中，只有NADPH氧化速率和细胞色素P - 450还原速率显著增加。NADPH利用与底物氧化的有效偶联似乎是多胺刺激外源化合物氧化的潜在机制。
