Hepatotoxicity of T-2 toxin, trichothecene mycotoxin

Five-week-old female ICR:CD-1 mice were inoculated orally with 10 mg/kg b.w. of T-2 toxin. Hematological and blood biochemical examinations and histopathological examination of the liver were done up to 48 hours after treatment (HAT). In addition, microarray analysis was done on the gene expression profile of the liver at 0.5, 3 and 24 HAT. In the T-2 toxin-treated group, the levels of AST and ALT increased while those of total cholesterol, total protein, blood glucose and fibrinogen decreased at and after 3 HAT. The coagulation test revealed the prolongation of both prothrombin time (PT) and activated partial thromboplastin time (APTT). Histopathologically, dead hepatocytes were sporadically observed at and after 3 HAT. Dead hepatocytes at the early stage were characterized by cellular swelling and those at the late stage by pyknosis with condensed eosinophilic cytoplasm, respectively. Microarray analysis on the liver revealed the up-regulated expression of oxidative stress-, cell cycle- and apoptosis-related genes and the down-regulated expression of lipid metabolism-, glycogen metabolism-, drug metabolism- and blood coagulation-related genes. Especially, c-fos and c-jun mRNAs expression was significantly elevated immediately after T-2 toxin-treatment and kept high level until 24 HAT. The present study clarified that T-2 toxin affects liver function including blood coagulation system and that morphological characteristic of dead hepatocytes shifts from cellular swelling (necrosis) to pyknosis with condensed eosinophilic cytoplasm (apoptosis). From the results of microarray analysis, T-2 toxin was considered to damage hepatocytes mainly through oxidative stress and apoptosis.