Effects of 8-methoxypsoralen on the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in mice.
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| Abstract |
8-Methoxypsoralen (8-MOP) is a well established drug in the treatment of various skin diseases. Pretreatment of mice with 8-MOP before administration of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) significantly reduced the incidence of NNK-induced tumor. The present study was designed to evaluate the in vivo effects of 8-MOP on the bioactivation of NNK in mice. Decrease in the α-hydroxylation of NNK in mouse blood and tissues was observed as the most pronounced effect of 8-MOP. The catalytic property of cytochrome P450 2A5 (CYP2A5) enzyme in mice was determined by the coumarin 7-hydroxylation reaction, suggesting that 8-MOP produced remarkable inhibition on CYP2A5 in female C57BL/6 mice. These results implied that 8-MOP could prevent NNK-induced mutagenesis and tumorigenesis in mice through the inhibition of NNK α-hydroxylation, which may be achieved through the effect of 8-MOP on the bioactivities of CYP2A5.
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| Authors | Mingfei Feng, Hongtu Zhang, Baojun Cao, Shuaidong Liu, Jian Mao, Qidong Zhang |
| Journal | Drug metabolism and pharmacokinetics (Drug Metab Pharmacokinet) Vol. 30 Issue 4 Pg. 314-20 (Aug 2015) ISSN: 1880-0920 [Electronic] England |
| PMID | 26210672 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2015 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved. |
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