Species difference of T-2 toxin metabolism in liver microsomes by high performance liquid chromatography-tandem mass spectrometry / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To compare the species difference of T-2 toxin metabolism in liver micro-somes of different animals. METHODS T-2 toxin was incubated with liver microsomes from mice, rats,Beagle dogs, monkeys and humans, respectively, at 37℃ for some time. Then, the incubation liquid was detected by high liquid chromatography-mass spectrometry method after albumen precipitation. RESULTS The half-life (t1/2) of T-2 toxin was less than 1 min, 2-4 min in mouse and monkey liver microsomes, 13 min in dog liver microsomes, and 39 min in rat liver microsomes. The hepatic clear-ance (Clh) of T-2 toxin was divided into three groups among the five species of animalshumans, dogs and rats were in one group, monkeys a second group, and mice in another group. The Clh of mouse group was 3-4 times that of the human, dog and rat group. The affinity to T-2 toxin was different between the liver microsomes of these five species. The affinity of mouse liver microsomes was the strongest, followed by that of humans, dogs, rats and monkeys. The enzyme transfer rate of T-2 toxin was the highest in monkey liver microsomes followed by that of rats and dogs. It was one million times higher in monkey liver microsomes than in human and mouse liver microsomes. The major metabolites were 3′-hydroxyl-T-2 toxin and neosolaniol. T-2 triol and HT-2 toxins were the major metabolites in human and rat liver microsomes. HT-2 toxin and 3′-OH-T-2 toxin were the dominating metabolites in dog liver microsomes and T-2 triol and 3′-OH-T-2 toxin in mouse liver microsomes. T-2 toxin metabolited by hydrolysis effect in mouse, rat, dog and human liver microsomes, but through hydroxylation in monkey liver microsomes. CONCLUSION There are species differences in metabolic parameters, metabolites, amounts of metabolites, metabolic pathways of T-2 toxin in mouse, rat, dog, monkey and human liver microsomes.