Biliary Excretion and Enterohepatic Cycling of Zearalenone in Immature Pigs

The disposition of the estrogenic mycotoxin, zearalenone (ZEN) in female, 10- to 14-week-old Yorkshire pigs was investigated. Pigs were administered [ 3H]ZEN intravenously (IV; n = 4; 5 mg/kg; 15 μCi/kg), orally ( n = 4; 10 mg/kg; 30 μCi/kg), or intravenously with bile removal (IVB; n = 2; 5 mg/kg; 15 μCi/ kg). Plasma, urine, feces, and bile (IVB pigs only) were serially collected and analyzed for radioactivity. Metabolite profiles were determined in plasma and bile by HPLC. The biological half-life of total plasma radioactivity in IV and orally dosed pigs (86.6 hr) was much larger than that of IVB animals (3.34 hr). Metabolite profiles of plasma concentration vs time demonstrated secondary peaks in concentration during the terminal elimination phase in IV and orally dosed pigs. In IVB pigs these peaks were absent, relative metabolite profiles were altered, and ZEN and metabolites were no longer detectable after 16 hr post-dosing. Biliary recovery of radioactivity, principally as glucuronide conjugates, was extensive (45.61 ± 4.73%) in IVB pigs and significantly greater ( p < 0.05) than that of fecal recovery of radioactivity in IV (6.56 ± 0.78) or orally dosed (21.74 ± 1.56%) pigs. Intraduodenal administration of bile containing [ 3H]ZEN and metabolites resulted in recovery of 64.56 ± 4.89% of the dose in bile, 20.78 ± 3.94% in urine, and the presence of glucuronide conjugates of ZEN and α-zearalenol (ZEL) in portal and jugular plasma. Differences in metabolite profiles between administered bile and sampled plasma suggest that the intestinal mucosa was active in reducing ZEN to ZEL and conjugating these metabolites with glucuronic acid. These studies provide evidence for extensive biliary secretion and enterohepatic cycling of ZEN and metabolites in pigs.