Modification of in vitro metabolism of T-2 toxin by esterase inhibitors.
In vitro metabolism of T-2 toxin with S-9 fraction obtained from livers of phenobarbital-treated pigs and rats in the presence of different esterase inhibitors, including NaF, p-hydroxymercuribenzoate, phenylmethylsulfonyl fluoride, eserine sulfate, diisopropylfluorophosphate, and diethyl p-nitrophenyl phosphate, was studied. The metabolism was completely shifted to the hydroxylation at the C-3' position in the T-2 toxin molecule when esterase inhibitors were present. Diethyl p-nitrophenyl phosphate was found to be the most potent among six esterase inhibitors tested. In the presence of 10(-4) M diethyl p-nitrophenyl phosphate, 3'-hydroxy-T-2 toxin was the only metabolite detected. Similar results were obtained when other T-2-related metabolites were tested. The yield of conversion of T-2 toxin, acetyl T-2 toxin, HT-2 toxin and T-2 triol to their respective 3'-hydroxyl derivatives were 82, 73, 72, and 75%, respectively.
D000818:Animals; D002855:Chromatography, Thin Layer; D004950:Esterases / Q000037:antagonists & inhibitors*; D006900:Hydroxylation; D006902:Hydroxymercuribenzoates / Q000494:pharmacology; D066298:In Vitro Techniques; D007531:Isoflurophate / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010261:Paraoxon / Q000494:pharmacology; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012717:Sesquiterpenes / Q000378:metabolism*; D012969:Sodium Fluoride / Q000494:pharmacology; D013552:Swine; D013605:T-2 Toxin / Q000031:analogs & derivatives / Q000378:metabolism*
D006902:Hydroxymercuribenzoates; D012717:Sesquiterpenes; D007531:Isoflurophate; D010664:Phenylmethylsulfonyl Fluoride; D012969:Sodium Fluoride; D010830:Physostigmine; D004950:Esterases; D013605:T-2 Toxin; C012351:HT-2 toxin; D010261:Paraoxon