title: The inhibitory effect of tannic acid on cytochrome P450 enzymes and NADPH-CYP reductase in rat and human liver microsomes.
abstract: Tannic acid has been shown to decrease mutagenicity and/or carcinogenicity of several amine derivatives and polycyclic aromatic hydrocarbons in rodents. The purpose of this study was to evaluate the effect of tannic acid on cytochrome P450 (CYP)-catalyzed oxidations using rat liver microsomes (RLM) and human liver microsomes (HLM) as the enzyme sources. In RLM, tannic acid showed a non-selective inhibitory effect on 7-methoxyresorufin O-demethylation (MROD), 7-ethoxyresorufin O-deethylation (EROD), tolbutamide hydroxylation, p-nitrophenol hydroxylation and testosterone 6beta-hydroxylation activities with IC(50) values ranged from 14.9 to 27.4 microM. In HLM, tannic acid inhibited EROD, MROD and phenacetin O-deethylation activities with IC(50) values ranged from 5.1 to 7.5 microM, and diclofenac 4-hydroxylation, dextromethorphan O-demethylation, chlorzoxazone 6-hydroxylation and testosterone 6beta-hydroxylation with IC(50) values ranged from 20 to 77 microM. In baculovirus-insect cell-expressed human CYP 1A1 and 1A2, the IC(50) values of tannic acid for CYP 1A1- and 1A2-catalyzed EROD activities were 23.1 and 2.3 microM, respectively, indicating that tannic acid preferably inhibited the activity of CYP1A2. Tannic acid inhibited human CYP1A2 non-competitively with a Ki value of 4.8 microM. Tannic acid was also found to inhibit NADPH-CYP reductase in RLM and HLM with IC(50) values of 11.8 and 17.4 microM, respectively. These results suggested that the inhibition of CYP enzyme activities by tannic acid may be partially attributed to its inhibition of NADPH-CYP reductase activity.
authors.affiliation: Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35, Keyan Road, Zhunan Town, Miaoli County, Taiwan, ROC.
authors.forename: Hsien-Tsung
authors.initials: HT
authors.lastname: Yao
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Chang
authors.forename: Shih-Jung
authors.initials: SJ
authors.lastname: Lan
authors.forename: Teng-Kuang
authors.initials: TK
authors.lastname: Yeh
mesh_terms: D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000037:antagonists & inhibitors* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013634:Tannins / Q000494:pharmacology*
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D013634:Tannins; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase