The effects of subcutaneous administration of T-2 toxin on liver drug metabolizing enzymes in piglets

Abstract

T-2 toxin is one of trichothecenes, which are a structurally diverse group of toxic secondary metabolites produced by Fusarium and related species of fungi. The toxin usually contaminates cereal grains throughout the world. Although the pig is increasingly being used in pharmacological and toxicological studies, there is not enough information about the effects of T-2 toxin on drug-metabolizing enzymes in pigs. The purpose of this study is to investigate the effects of subcutaneous administration of T-2 toxin on the activities of hepatic Phase I and Phase II metabolizing enzymes in piglet liver. Piglets were administrated 0.3 mg T-2 toxin/Kg BW dissolved in DMSO by single subcutaneous (s.c.) injection. Control animals received only vehicle (DMSO). The activities of Phase I and Phase II enzymes were determined at 24 and 48 h after the last s.c. injection. The activities of cytochrome P-450 (CYP) 1A2 and 2E1 increased slightly at 24 and 48 h (P < 0.05). The CYP3A4 activity increased at 24 (P < 0.01), and tended to decrease at 48 h, but not significantly (P > 0.05). The glutathione S-transferase (GST) activity towards cumene hydroperoxide increased slightly at 24 h (P < 0.05), but decreased slightly at 48 h (P < 0.05). No significant changes were observed in the glutathione S-transferase activity toward 1-Chloro-2,4-dinitrobenzene (CDNB) either at 24 or 48 h. Western blot analyses of the liver fractions revealed increased levels of CYP1A2, 2E1, 3A4, GST, GST M1-1 at 24 h, and that of CYP2E1 at 48 h.The results suggest that T-2 toxin causes modulation of Phase I and Phase II drug metabolizing enzymes in piglets.

Keywords:

• T-2 toxin
• glutathione S-transferase (GST)
• cytochrome P-450(CYP)
• drug metabolizing enzymes
• western blotting assays
• piglets

Acknowledgements

The authors are grateful to Dr Junyou Li and Dr Tomohiro Yonezawa for their valuable help in this experiment. This work was supported by a grant from the Ministry of Education, Culture, Sports, Science and Technology, Grant No.: 15405039.