Metabolism and Clearance of T-2 Mycotoxin in Perfused Rat Livers
ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
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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, 3HT-2 toxin was delivered under constant perfusate flow 8 mlmin 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 3HT-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 3hydroxy HT-2, 3hydroxy T-2 triol, 4-deacetylneosolaniol, T-2 tetraol, and glucuronide conjugates of HT-2, 3hydroxy 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.