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S-equol glucuronidation in liver and intestinal microsomes of humans, monkeys, dogs, rats, and mice

Author:
Isobe, Takashi, Ohkawara, Susumu, Ochi, Sadayuki, Tanaka-Kagawa, Toshiko, Hanioka, Nobumitsu
Source:
Food and chemical toxicology 2019 v.131 pp. 110542
ISSN:
0278-6915
Subject:
daidzein, dogs, humans, intestines, kinetics, liver, liver microsomes, metabolites, mice, monkeys, rats, regioselectivity, toxicology, transferases
Abstract:
S-equol, an active metabolite of the soy isoflavone daidzein, is mainly metabolized into glucuronide(s) by UDP-glucuronosyltransferase (UGT) enzymes in mammals. In the present study, S-equol glucuronidation was examined in the liver and intestinal microsomes of humans, monkeys, dogs, rats, and mice using a kinetic analysis. CLint values for 7- and 4′-glucuronidation by liver microsomes were higher than those by intestinal microsomes in all species. CLint values for total glucuronidation (sum of 7- and 4′-glucuronidation) were rats (7.6) > monkeys (5.8) > mice (4.9) > dogs (2.8) > humans (1.0) for liver microsomes, and rats (9.6) > mice (2.8) > dogs (1.3) ≥ monkeys (1.2) > humans (1.0) for intestinal microsomes, respectively. Regarding regioselective glucuronidation by liver and intestinal microsomes, CLint values were 7-glucuronidation > 4′-glucuronidation for humans, monkeys, dogs, and mice, and 4′-glucuronidation > 7-glucuronidation for rats. These results suggest that the metabolic abilities of UGT enzymes toward S-equol in the liver and intestines markedly differ among humans, monkeys, dogs, rats, and mice.
Agid:
6461607