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.