Metabolism and Clearance of T-2 Mycotoxin in Perfused Rat Livers

Isolated perfused rat livers were used to study the metabolism and clearance of T-2 mycotoxin, a non-protein Fusarium metabolite known to cause illness or death on contact or by ingestion. To evaluate the in vitro hepatic metabolism, clearance and rate of biliary excretion of T-2 toxin, (3H)T-2 toxin was delivered under constant perfusate flow (8 ml/min) in a single-pass experiment. Steady-state conditions were achieved within 10 min as indicated by a constant exit rate of radiolabel in the effluent. At steady-state, 70 + or - 4% of the total delivered radiolabel was extracted by the liver, 38 + or - 4% remained in the perfusate. Liver actively metabolizes trichothecenes, therefore, the extraction ratio for total radiolabel does not reflect the actual extraction ratio for T-2 toxin. At steady-state, 93% of the delivered (3H)T-2 was extracted and metabolized by the liver, while 4.6 + or - 0.3% remained unmetabolized in the effluent perfusate. The excretion rate of metabolites and conjugates into bile was constant after a 10-min perfusion. Radioactivity measured in bile accounted for 55% of the total radiolabel delivered during the perfusion experiment (1 hr). T-2 toxin was metabolized and eliminated as 3'hydroxy HT-2, 3'hydroxy T-2 triol, 4-deacetylneosolaniol, T-2 tetraol, and glucuronide conjugates of HT-2, 3'hydroxy HT-2, and T-2 tetraol. These studies describe the use of a perfused organ system to determine the rate of formation of T-2 metabolites and their simulation into bile. See also AD-A167 978 and AD-A167 979.