Protective effect of ethyl pyruvate on pancreas injury in rats with severe acute pancreatitis.
BACKGROUND
Systemic inflammatory mediators have an important role in the development of acute pancreatitis. In this study, we investigated the effect of ethyl pyruvate (EP) on pancreas injury in rats with severe acute pancreatitis (SAP) and its possible mechanism.


METHODS
We randomly allocated rats into the following three experimental groups: control and SAP- and EP-treated. Then, we recorded the mortality rate. We harvested tissue specimens for morphological studies, streptavidin-peroxidase immunohistochemistry examination, and Western blot analysis. We tested the levels of pancreatic tissue malondialdehyde and the activity of serum amylase, myeloperoxidase in the pancreas. In addition, we studied nuclear factor-κB (NF-κB) activation, tumor necrosis factor-α levels, and high mobility group box 1 protein expression levels in the pancreas.


RESULTS
Treatment with EP after SAP was associated with a reduction in the severity of SAP and pancreas injury. Treatment with EP significantly decreased the expression of tumor necrosis factor-α and high mobility group box 1, and ameliorated malondialdehyde concentration and myeloperoxidase activity in the pancreas in SAP rats. Compared with the SAP group, treatment with EP significantly decreased the number of inflammatory cell infiltration, markedly inhibited pancreatic NF-κB DNA binding, and increased the survival rates.


CONCLUSIONS
This study demonstrates that preventing the activation of NF-κB by EP ameliorates tissue injury associated with experimental murine acute pancreatitis. This result provides an important insight into the molecular biology of acute pancreatitis.
Intensive Care Unit, First Hospital, China Medical University, Shenyang, China. zgl17698@sina.com
Zheng-Gang
ZG
Luan
Xiao-Chun
XC
Ma
Hao
H
Zhang
Cheng
C
Zhang
Ren-Xuan
RX
Guo
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D004247:DNA / Q000378:metabolism; D024243:HMGB1 Protein / Q000032:analysis; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy*; D009195:Peroxidase / Q000378:metabolism; D011773:Pyruvates / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D016328:NF-kappa B; D011773:Pyruvates; D014409:Tumor Necrosis Factor-alpha; C046522:ethyl pyruvate; D004247:DNA; D009195:Peroxidase; D000681:Amylases