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


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.


CONCLUSIONS
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.
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, People's Republic of China.
Miao
M
Shen
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, People's Republic of China.
Jie
J
Lu
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, People's Republic of China.
Ping
P
Cheng
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, People's Republic of China.
Chunlei
C
Lin
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, People's Republic of China.
Weiqi
W
Dai
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, People's Republic of China.
Fan
F
Wang
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, People's Republic of China.
Chengfen
C
Wang
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, People's Republic of China.
Yan
Y
Zhang
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, People's Republic of China.
Kan
K
Chen
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, People's Republic of China.
Ling
L
Xu
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, People's Republic of China.
Yinqun
Y
Zhou
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, People's Republic of China.
Chuanyong
C
Guo
D000818:Animals; D015153:Blotting, Western; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D003208:Concanavalin A / Q000633:toxicity*; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism; D019693:Hepatitis, Autoimmune / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D007124:Immunoenzyme Techniques; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000633:toxicity*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011773:Pyruvates / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D024243:HMGB1 Protein; D007376:Interleukin-2; D015850:Interleukin-6; D008934:Mitogens; D016328:NF-kappa B; D011773:Pyruvates; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C046522:ethyl pyruvate; D003208:Concanavalin A