Zearalenone is bioactivated in the river Buffalo (<Emphasis Type="Italic">Bubalus bubalis</Emphasis>): hepatic biotransformation |
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Authors: | Malekinejad Hassan Rahmani Fatemeh Bahrampour Kobra |
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Institution: | (1) Department of Pharmacology & Toxicology, Faculty of Veterinary Medicine, Urmia University, P.O. Box 1177, Urmia, Iran;(2) Department of Biology, Division of Molecular Genetics, Faculty of Basic Sciences, Urmia University, Urmia, Iran |
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Abstract: | Zearalenone (ZEA) as a mycoestrogen is found frequently in human foods and animal feeds. Its estrogenic effects depend on
its biotransformation fate including both first- and second-phase reactions, which are predominantly governed by hydroxylation
and glucuronidation, respectively. In this study, we investigate the hepatic biotransformation of ZEA in river buffalo. To
evaluate the hepatic biotransformation of ZEA, both subcellular fractions of the liver were prepared. ZEA was incubated with
intracellular subfractions in the presence of nicotinamide dinucleotide phosphate, and the products were determined by means
of high-performance liquid chromatography. Moreover, in the same frame of experiment and in the presence of uridine diphosphate
glucuronic acid, the rate of glucuronidation for substrate and products were estimated as well. We found that α-zearalenol
(α-ZOL) is the major hydroxylated hepatic metabolite of ZEA produced by both studied subcellular fractions. The enzymatic
kinetics analyses indicated that the α-ZOL and β-ZOL production by microsomal fraction were two- and three-fold higher than
those by postmitochondrial fraction, respectively. The calculated data showed that α-ZOL is conjugated with glucuronic acid
more than ZEA and β-ZOL, especially at the lower concentrations, which seems to be more applicable. Our data suggest that
unlike other domestic ruminants including cattle and sheep, the hepatic biotransformation of ZEA in river buffalo results
in bioactivation and formation of potent estrogenic metabolite. Moreover, at the relevant concentrations, the produced potent
estrogenic metabolite is entirely conjugated with glucuronic acid and, consequently, may cause the prolongation of presence
of the compound in the body due to enterohepatic cycle. |
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