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 6β-hydroxylation activities with IC 50 values ranged from 14.9 to 27.4 μM. In HLM, tannic acid inhibited EROD, MROD and phenacetin O-deethylation activities with IC 50 values ranged from 5.1 to 7.5 μM, and diclofenac 4-hydroxylation, dextromethorphan O-demethylation, chlorzoxazone 6-hydroxylation and testosterone 6β-hydroxylation with IC 50 values ranged from 20 to 77 μM. 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 μM, 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 μM. Tannic acid was also found to inhibit NADPH-CYP reductase in RLM and HLM with IC 50 values of 11.8 and 17.4 μM, 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.