Abstract.
Eight toxic compounds of natural origin present in the human diet or used as drugs were tested as inhibitors of UDP-glucuronosyltransferase (UGT) activity in rat liver microsomes with 1-naphthol (1-NA), phenolphthalein (PPh) and 4-nitrophenol (4-NP) as substrates. Strong inhibitory effects were observed with tannic acid (tannin) and the antifungal drug griseofulvin (GF): at a concentration of 1 mM, the two compounds completely suppressed the glucuronidation of 1-NA and PPh, respectively. A concentration of 0.1 mM still proved to be highly inhibitory, and even at a concentration as low as 50 µM, tannin produced nearly 50% inhibition of 1-NA conjugation. The UGT isoforms converting 4-NP were less sensitive to the tested compounds (with the exception of GF). Kinetic studies with tannin revealed an uncompetitive type of inhibition toward 1-NA, with an apparent Ki value of 20 µM. The inhibition by GF was non-competitive with respect to PPh and was of a mixed type toward UDP-glucuronic acid, with apparent Ki values of 40 µM and 30 µM, respectively. Tannin and GF did not act as substrates for rat microsomal UGT.
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Grancharov, K., Engelberg, H., Naydenova, Z. et al. Inhibition of UDP-glucuronosyltransferases in rat liver microsomes by natural mutagens and carcinogens. Arch Toxicol 75, 609–612 (2001). https://doi.org/10.1007/s00204-001-0282-x
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DOI: https://doi.org/10.1007/s00204-001-0282-x