Inhibition of liver microsomal cytochrome P450 activity and metabolism of the tobacco-specific nitrosamine NNK by capsaicin and ellagic acid.

ABSTRACT

The tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK), present in tobacco and tobacco smoke, is metabolically activated by microsomal enzymes. In this study, we examined the effect of capsaicin and ellagic acid on the in vitro metabolism of NNK by hamster and rat liver microsomes. Capsaicin is the principal component of Capsicum fruits used widely throughout the world as a food additive. Ellagic acid, with reported anticarcinogenic properties, is found in various soft fruits and nuts. Both capsaicin and ellagic acid inhibited the major pathways of NNK-reduction, N-pyridine oxidation and a-hydroxylation by hamster liver microsomes. Capsaicin inhibited NNK-reduction and a-hydroxylation and ellagic acid inhibited N-oxidation and a-hydroxylation by rat liver microsomes. The effects of capsaicin and ellagic acid on isozymes of cytochrome P450 were observed in the hydroxylation reactions of the metabolism of the steroid hormone testosterone. Results of these experiments indicated that both capsaicin and ellagic acid strongly inhibited the constitutive enzymes CYP 2A2, 3A1, 2C11, 2B1, 2B2 and 2C6. This study suggests that capsaicin and ellagic acid, as naturally occurring dietary constituents, possess antimutagenic and anticarcinogenic properties through the inhibition of xenobiotic metabolizing enzymes.