Ethyl pyruvate pretreatment attenuates concanavalin a-induced autoimmune hepatitis in mice

PLoS One. 2014 Feb 3;9(2):e87977. doi: 10.1371/journal.pone.0087977. eCollection 2014.


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-κB) activity were determined.

Results: Following Con A challenge, cytokines TNF-α, IL-2, IL-1β 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-α, IL-2, IL-6 and IL-1β at 3h and 6h and the level of HMGB1 at 6h and 24h post injection. Ethyl pyruvate blocked the degradation of IκB α and IκB β and decreased the expression of NF-κB at 24h.

Conclusion: Taken together, these results indicated that ethyl pyruvate protected against Con A-induced autoimmune hepatitis by decreasing both early (TNF-α, IL-2, IL-1β and IL-6) and late (HMGB1) cytokine expression in mice. The reduction of HMGB1 may correlate with the amelioration of NF-κB activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Concanavalin A / toxicity*
  • HMGB1 Protein / genetics
  • HMGB1 Protein / metabolism
  • Hepatitis, Autoimmune / etiology
  • Hepatitis, Autoimmune / metabolism
  • Hepatitis, Autoimmune / prevention & control*
  • Immunoenzyme Techniques
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mitogens / toxicity*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Pyruvates / pharmacology*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • HMGB1 Protein
  • Interleukin-2
  • Interleukin-6
  • Mitogens
  • NF-kappa B
  • Pyruvates
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • ethyl pyruvate
  • Concanavalin A

Grant support

This work was supported by the National Natural Science Foundation of China (No.81101579 and 81270515), the Shanghai Science and Technology Innovation Plan of Action for international cooperation projects (No. 11430702400), the China Foundation for Hepatitis Prevention and Control WBN Liver Disease Research Fund (No. 20100021 and 20120005), and the Shanghai Health Bureau issues (No. 2011287 and 2012107). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.