Ethyl Pyruvate Pretreatment Attenuates Concanavalin A-Induced Autoimmune Hepatitis in Mice

Pharmacological Relevance: Ethyl pyruvate (EP), a potent reactive oxygen species scavenger, has been reported to contribute to the inflammatory process. However, the protective effect of ethyl pyruvate on Concanavalin A (Con A)-induced autoimmune hepatitis have not been explored. Thus, the aims of this study are to investigate both the effects of ethyl pyruvate and its mechanism of protection on Con A-induced autoimmune hepatitis in mice. Materials and Methods: Acute autoimmune hepatitis was induced by Con A (20 mg/kg) in Balb/C mice; ethyl pyruvate (40 mg/kg and 80 mg/kg) was administrated 1h prior to the Con A injection. At 3h, 6h and 24h post Con A injection, histological grading, proinflammatory cytokine levels and nuclear factor kappa B (NF-kappa B) activity were determined. Results: Following Con A challenge, cytokines TNF-alpha, IL-2, IL-1 beta and IL-6 were expressed at 3h and 6h, and the level of HMGB1 significantly increased by 24h. Pretreatment with ethyl pyruvate ameliorated the pathological effects of Con A-induced autoimmune hepatitis and significantly decreased the levels of TNF-alpha, IL-2, IL-6 and IL-1 beta at 3h and 6h and the level of HMGB1 at 6h and 24h post injection. Ethyl pyruvate blocked the degradation of I kappa B alpha and I kappa B beta and decreased the expression of NF-kappa B at 24h. Conclusion: Taken together, these results indicated that ethyl pyruvate protected against Con A-induced autoimmune hepatitis by decreasing both early (TNF-alpha, IL-2, IL-1 beta and IL-6) and late (HMGB1) cytokine expression in mice. The reduction of HMGB1 may correlate with the amelioration of NF-kappa B activity.