Selective induction of rat hepatic CYP1 and CYP4 proteins and of peroxisomal proliferation by green tea.
Rats were exposed to freshly prepared aqueous extracts of green tea (2.5% w/v) as the sole source of drinking water for 4 weeks. Hepatic cytochrome P450 activity was determined using chemical probes, showing selectivity for particular isoforms, and by immunoblot analysis employing polyclonal antibodies. Exposure to green tea gave rise to increases in the O-demethylation of methoxyresorufin and, to a lesser extent, in the dealkylations of ethoxyresorufin and pentoxyresorufin. An increase was also seen in lauric acid hydroxylation but, in contrast, the N-demethylation of erythromycin was inhibited. p-Nitrophenol oxidase activity was unaffected by the same treatment. Immunoblot analysis revealed increases in the apoprotein levels of CYP1A2 and CYP4A1 following treatment with green tea. A significant increase was also noted in the CN(-)-insensitive palmitoyl CoA oxidation and this was paralleled by an increase in the levels of the peroxisomal trifunctional protein determined immunologically. Hepatic S9 and microsomal preparations from tea-treated animals were more effective than controls in activating 2-amino-3-methylimidazol[4,5-f]quinoline and 2-aminoanthracene to mutagens in the Ames test. When N-nitrosopyrrolidine served as the promutagen, tea did not influence its mutagenicity when isolated microsomes comprised the activation system but a significant inhibition was observed when hepatic S9 was used. The above findings are discussed within the context of the established anticarcinogenic and anti-mutagenic properties of green tea.
Division of Toxicology, School of Biological Sciences, University of Surrey, Guildford, UK.
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Bu-Abbas
M N
MN
Clifford
R
R
Walker
C
C
Ioannides
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D019388:Cytochrome P-450 CYP1A2; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008830:Microbodies / Q000187:drug effects*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D010088:Oxidoreductases / Q000096:biosynthesis*; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013662:Tea
D010936:Plant Extracts; D013662:Tea; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D019388:Cytochrome P-450 CYP1A2; D042926:Cytochrome P-450 CYP4A