Polyamine effects on cytochrome P-450- and flavin-containing monooxygenase-mediated oxidation of xenobiotics.
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.[1]References
- Polyamine effects on cytochrome P-450- and flavin-containing monooxygenase-mediated oxidation of xenobiotics. Osimitz, T.G., Kulkarni, A.P. Drug Metab. Dispos. (1985) [Pubmed]
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