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Therapeutic Treatment With Ethyl Pyruvate Attenuates the Severity of Liver Injury in Rats With Severe Acute Pancreatitis

Objective The objective of the study was to evaluate the effect of ethyl pyruvate (EP) in ameliorating liver injury in rats with severe acute pancreatitis (SAP) and its possible mechanism. Methods Rats were randomly divided into control group, SAP group, and EP-treated group. Then, the tissue specimens were harvested for morphological studies, immunohistochemistry examination, reverse transcriptase–polymerase chain reaction, and Western blot analysis. The DNA-binding activity of nuclear factor &kgr;B was measured by electrophoretic mobility shift assay. The concentrations of serum amylase, alanine aminotransferase, and pancreatic tissue malondialdehyde and the activity of myeloperoxidase in the liver were determined. Results Treatment with EP after SAP was associated with a reduction in the severity of SAP and liver injury. Treatment with EP significantly decreased the hepatic mRNA expression of tumor necrosis factor &agr; and interleukin 1&bgr; and ameliorated the activity of myeloperoxidase in the liver in SAP rats. Compared with the SAP group, treatment with EP significantly decreased the infiltration of inflammatory cells and markedly inhibited hepatic nuclear factor &kgr;B DNA binding; EP therapy dramatically inhibited high-mobility group box 1 expression from inflamed hepatic tissue. Conclusions Our results demonstrate that EP might play a therapeutic role in liver inflammation in this SAP model, and these beneficial effects of EP are because of the modulation of high-mobility group box 1 and other inflammatory cytokine responses. Abbreviations SAP - severe acute pancreatitis EP - ethyl pyruvate HMGB1 - high-mobility group box 1 MPO - myeloperoxidase MDA - malondialdehyde ALT - alanine aminotransferase NF-&kgr;B - nuclear factor &kgr;B TNF-&agr; - tumor necrosis factor &agr; IL-1&bgr; - interleukin-1&bgr; EMSA - electrophoretic mobility shift assay