Fate and Distribution of 3H-Labeled T-2 Mycotoxin in Guinea Pigs

摘要

T-2 toxin is a potent cytotoxic metabolite produced by the Fusarium species. The fate and distribution of (3H)-labeled T-2 toxin were examined in male guinea pigs. Radioactivity was detected in all body tissues within 30 min after an im injection of an LD(50) dose (1.04 mg/kg) of T-2 toxin. The plasma concentration curve of radioactivity versus time was multiphasic, with an initial absorption half-life (T1/2,E) of less than 6 min. The initial half-life of elimination (T1/2,A) was 1.8 hr. Bile contained a large amount of radioactivity which was identified as HT-2,4-deacetylneosolaniol, 3'hydroxy HT-2, 3'hydroxy T-2 triol, and several more-polar unknowns. These T-2 metabolites are excreted from liver via bile into the intestine. Wtihin 5 days, 75% of the total radioactivity was excreted in urine and feces at a ratio of 4 to 1. The appearance of radioactivity in the excreta was biphasic (T1/2,A=2.2 hr, 1.5 days and 8.2 hr, 1.7 days, for urine and feces, respectively). Metabolic derivatives of T-2 excreted in urine were T-2 tetraol, 4-deacetylneosolaniol, 3' hydroxy HT-2, and several unknowns. These studies showed a rapid appearance in and subsequent loss of radioactivity from tissues and body fluids. However, radioactivity (ten to the fifth power dpm) was still detectable in tissues at 28 days. The distribution patterns and excretion rates suggest that liver and kidney are the principal organs of detoxication and excretion of T-2 toxin and its metabolites.