Abstract: Objective: To explore the protective effect of betulinic acid (BA) on liver injury induced by T-2 toxin in mice and its underlying molecular mechanism. Methods: Totally 60 adult male Kunming mice were randomly divided into six groups: blank control, 4 mg/kg mb T-2 toxin, 0.25 mg/kg mb BA + T-2, 0.5 mg/kg mb BA + T-2, 1 mg/kg mb BA + T-2 and 100 mg/kg mb vitamin E (VE) + T-2. After 14 days of continuous administration of betulinic acid, T-2 toxin was intraperitoneally injected into all groups except the blank control group to induce liver injury. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) and total protein (TP) concentration in serum were measured. Histopathological changes in the liver were observed by hematoxylin-eosin staining. Total antioxidant capacity (T-AOC), the activities of catalase (CAT) and superoxide dismutase (SOD), and the contents of glutathione (GSH) and malondialdehyde (MDA) in liver tissues were determined. Apoptosis of hepatocytes was detected by TUNEL staining. The protein expression of Bax, Bcl-2, caspase-3, Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) in liver tissues was evaluated by Western blot. Results: BA pretreatment attenuated the increase in the activities of ALT, AST and ALP and the decrease in TP concentration in serum caused by T-2 toxin. Also, it increased T-AOC, CAT and SOD activity and GSH content, decreased MDA content and the number of apoptotic cells, up-regulated the expression of Bcl-2 protein, and down-regulated the expression of Bax, caspase-3, JAK2, and STAT3 proteins. Conclusion: BA inhibits hepatocyte apoptosis through the JAK2/STAT3 pathway due to its antioxidant capacity, thereby alleviating T-2-induced liver injury in mice.

Key words: betulinic acid; T-2 toxin; liver damage; oxidative stress; apoptosis