| ABSTRACT: |
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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. |