Comparative in vitro metabolism of T-2 toxin by hepatic microsomes prepared from phenobarbital-induced or control rats, mice, rabbits and chickens.
Hepatic microsomes were prepared from phenobarbital (PB)-treated and control rats, mice, rabbits and chickens and were incubated with T-2 toxin (100 micrograms/mg microsomal protein). Additional microsomes from PB-induced animals were incubated with T-2 toxin and the esterase inhibitor paraoxon (PA) at 2.5 nmol/mg microsomal protein. The major metabolite in microsomal preparations from both control and PB-induced rats, rabbits and mice was HT-2. In microsomes isolated from PB-treated chickens, 3'-hydroxy T-2 was the major metabolite, but 30 and 79% of the added T-2 toxin remained unmetabolized at 60 min in incubations from PB-induced and control birds, respectively. The percentage of hydroxylated metabolites formed in the microsomal preparations of the four species studied was significantly increased following PB treatment compared with the non-treated controls. The addition of PA to the incubation system effectively inhibited the hydrolysis of the ester groups in T-2 toxin, resulting in 1.4- and 1.25-fold increases in the percentage of 3'-hydroxy T-2 in the mouse and rat microsomal samples, respectively. In the rabbit microsomal preparations, 3'-hydroxy T-2, which was not detected in the absence of PA, represented 11% of the added substrate in the PB/PA incubation samples. Addition of PA did not cause a significant change in the amount of 3'-hydroxy T-2 formed in chicken microsomal samples, since competition between hydrolysis and hydroxylation pathways for the T-2 toxin substrate was not an important factor in this species. Two new metabolites, designated RLM-2 and RLM-3 were detected in chicken, rat and mouse microsomal preparations. On the basis of gas chromatography/mass spectrometry data, the compounds were tentatively identified as isomers of 3'-hydroxy T-2.
Knupp
C A
CA
Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois, Urbana 61801.
Swanson
S P
SP
Buck
W B
WB
D000818:Animals; D002645:Chickens; D006900:Hydroxylation; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D010261:Paraoxon / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012717:Sesquiterpenes / Q000378:metabolism*; D013045:Species Specificity; D013605:T-2 Toxin / Q000378:metabolism* / Q000633:toxicity
D012717:Sesquiterpenes; D013605:T-2 Toxin; D010261:Paraoxon; D010634:Phenobarbital