A comparison of hepatic in vitro metabolism of T-2 toxin in rats, pigs, chickens, and carp

Abstract

1. T-2 toxin, a highly toxic member of the type-A trichothecenes, is produced by various Fusarium moulds that can potentially affect human health. It is strongly cytotoxic for human hematopoietic progenitors. Alimentary toxic aleukia (ATA), a disease typically associated with human, is primarily induced by T-2 toxin.

2. A comparison of the metabolism of T-2 toxin incubated with hepatocytes of rats, piglets, chickens, and the hepatic subcellular fractions (microsomes and cytosol) of piglets, chickens, rats, and carp (common carp and grass carp) was carried out. The activities of the recombinant pig CYP3A29 on the transformation of T-2 and HT-2 toxins were preliminary studied. Metabolites were identified by novel LC/MS-IT-TOF.

3. Qualitative similarities and differences across the species were observed. In liver microsomes, HT-2 toxin, neosolaniol (NEO), 3′-OH-T-2, and 3′-OH-HT-2 were detected in rats, chickens, and pigs. 3′-OH-HT-2 and HT-2 toxin was not detectable in common carp and grass crap, respectively. Moreover, in liver microsomes, the hydroxyl metabolites accounted for the largest percentage in carp, whereas the hydrolysis product, HT-2 toxin, was the major one for the land animals. Only hydrolysis products such as NEO and HT-2 toxin were detected in hepatocytes. Recombinant pig CYP3A29 was able to convert T-2 and HT-2 toxins to high rates of 3′-OH-T-2 and 3′-OH-HT-2, respectively. Both CYP450 and carboxylesterase enzymes have been found to play a role in the metabolism of T-2 toxin.

4. Metabolism of T-2 toxin across species produces a similar spectrum of metabolites. Preliminary metabolic studies of carp reveal that ester hydrolysis of T-2 toxin in carp may not play as important a role as is the case with land animals.

Keywords::

• Comparative metabolism
• T-2 toxin
• carp
• toxicity
• liver
• CYP3A29