Effects of 8-methoxypsoralen on the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in mice. Issue 4 (August 2015)

• Record Type: Journal Article
• Authors: Feng, Mingfei; Zhang, Hongtu; Cao, Baojun; Liu, Shuaidong; Mao, Jian; Zhang, Qidong
• Is Part Of: Drug metabolism and pharmacokinetics. Volume 30:Issue 4(2015)
• Page Start: 314
• Page End: 320
• Publication Date: 2015-08
• Subjects: 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone -- CYP2A5 -- 8-Methoxypsoralen -- Activity -- Metabolites -- Mice; Drugs -- Metabolism -- Periodicals; Pharmacokinetics -- Periodicals; 615.7
• DOI: 10.1016/j.dmpk.2015.06.001
• Languages: English
• ISSNs: 1347-4367

Abstract

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.