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 nonprotein 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, 33.9 micrograms T-2/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, 93 +/- 4% of the delivered [3H]T-2 was extracted and metabolized by the liver, while 4.6 +/- 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. Approximately 7% of the administered radiolabel remained in the liver and was identified as 4-deacetylneosolaniol (18%), T-2 tetraol (41%), and conjugated metabolites (41%). Total recovery of administered radiolabel associated with T-2 and its metabolites equaled 97.6% (bile, 52.5%; perfusate, 38.0%; liver, 7.1%). Approximately 3% of the biliary radiolabel was not identified. These studies describe the use of a perfused organ system to determine the rate of formation of T-2 metabolites and their elimination into bile.