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 κB 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 α and interleukin 1β 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 κB 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.
Department of Intensive Care Unit, The First Hospital, China Medical University, Shenyang, China. zgl17698@sina.com
Zheng-Gang
ZG
Luan
Hao
H
Zhang
Xiao-Chun
XC
Ma
Cheng
C
Zhang
Ren-Xuan
RX
Guo
D000208:Acute Disease; D000818:Animals; D015153:Blotting, Western; D015870:Gene Expression / Q000187:drug effects; D024243:HMGB1 Protein / Q000378:metabolism; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D009195:Peroxidase / Q000378:metabolism; D011773:Pyruvates / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D013656:Taurocholic Acid; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D024243:HMGB1 Protein; D007375:Interleukin-1; D016328:NF-kappa B; D011773:Pyruvates; D014409:Tumor Necrosis Factor-alpha; C046522:ethyl pyruvate; D008315:Malondialdehyde; D013656:Taurocholic Acid; D009195:Peroxidase