Effect of UDP-glucuronyltransferase induction on zearalenone metabolism.
Experiments were conducted to determine the UDP-glucuronyltransferase (UDP-GT) isoenzyme which catalyzes zearalenone (Z) conjugation, and the effect of increased enzyme activity on Z metabolism. In competitive enzyme assays, the activity of rat liver UDP-GT towards Z was inhibited by 1-naphthol (NA), a GT1 substrate, and 4-hydroxybiphenyl (HB), a GT2 substrate. When enzyme activity was induced with either 3-methylcholanthrene (MC), a GT1 inducer, or phenobarbital (PB), a GT2 inducer, increased UDP-GT activity towards Z, NA and HB was observed. UDP-GT induction by PB increased urinary excretion of conjugated alpha-zearalenol. These results indicate that UDP-GT isoenzymes have overlapping substrate specificities, and that Z detoxification may be enhanced by UDP-GT enzyme induction, resulting in increased urinary excretion of conjugated alpha-zearalenol.
Pandey
A
A
Department of Foods and Nutrition, University of Manitoba, Winnipeg, Canada.
Hassen
A M
AM
Benedict
D R
DR
Fitzpatrick
D W
DW
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008658:Inactivation, Metabolic / Q000502:physiology; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008748:Methylcholanthrene / Q000494:pharmacology; D009284:Naphthols / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012118:Resorcinols / Q000378:metabolism*; D015025:Zearalenone / Q000378:metabolism* / Q000494:pharmacology
D001713:Biphenyl Compounds; D007527:Isoenzymes; D009284:Naphthols; D012118:Resorcinols; C029350:1-naphthol; D008748:Methylcholanthrene; D015025:Zearalenone; C019046:4-phenylphenol; D014453:Glucuronosyltransferase; D010634:Phenobarbital