Ethyl pyruvate significantly inhibits tumour necrosis factor-α, interleukin-1β and high mobility group box 1 releasing and attenuates sodium taurocholate-induced severe acute pancreatitis associated with acute lung injury

Clin Exp Immunol. 2013 Jun;172(3):417-26. doi: 10.1111/cei.12062.

Abstract

In this study, we examined the effect of ethyl pyruvate (EP) on pulmonary inflammation in rats with severe pancreatitis-associated acute lung injury (ALI). Severe acute pancreatitis (SAP) was induced in rats by the retrograde injection of 5% sodium taurocholate into the pancreatic duct. Rats were randomly divided into the following experimental groups: control group, SAP group and EP-treated group. The tissue specimens were harvested for morphological studies, Streptavidin-peroxidase immunohistochemistry examination. Pancreatic or lung tissue oedema was evaluated by tissue water content. Serum amylase and lung tissue malondialdehyde (MDA) and myeloperoxidase (MPO) were measured. Meanwhile, the nuclear factor-κB (NF-κB) activation, tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels and HMGB1 protein expression levels in the lung were studied. In the present study, we demonstrated that treatment with EP after SAP was associated with a reduction in the severity of SAP and lung injury. Treatment with EP significantly decreased the expression of TNF-α, IL-1β, HMGB1 and ameliorated MDA concentration, MPO activity in the lung in SAP rats. Compared to SAP group, administration of EP prevented pancreatitis-induced increases in nuclear translocation of NF-κB in the lung. Similarly, treatment with EP significantly decreased the accumulation of neutrophils and markedly reduced the enhanced lung permeability. In conclusion, these results demonstrate that EP might play a therapeutic role in pulmonary inflammation in this SAP model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / etiology
  • Acute Lung Injury / immunology*
  • Acute Lung Injury / pathology
  • Amylases / blood
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • HMGB1 Protein / antagonists & inhibitors*
  • Interleukin-1beta / antagonists & inhibitors*
  • Lung / drug effects
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Malondialdehyde / metabolism
  • Pancreatitis / complications
  • Pancreatitis / drug therapy*
  • Pancreatitis / immunology*
  • Pancreatitis / pathology
  • Peroxidase / metabolism
  • Pyruvates / therapeutic use*
  • Rats
  • Rats, Wistar
  • Taurocholic Acid / toxicity
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • HMGB1 Protein
  • Hbp1 protein, rat
  • Interleukin-1beta
  • Pyruvates
  • Tumor Necrosis Factor-alpha
  • ethyl pyruvate
  • Malondialdehyde
  • Taurocholic Acid
  • Peroxidase
  • Amylases