Ethyl pyruvate reduces acute lung damage following trauma and hemorrhagic shock via inhibition of NF-κB and HMGB1

Immunobiology. 2018 Mar;223(3):310-318. doi: 10.1016/j.imbio.2017.10.037. Epub 2017 Oct 16.


Objective: After blunt thoracic trauma (TxT) and hemorrhagic shock with resuscitation (H/R) intense local inflammatory response and cell loss frequently impair the pulmonary function. Ethyl pyruvate (EP) has been reported to improve the pathophysiologic derangements in models of acute inflammation. Here, we studied the effects of EP on inflammation and lung damage after TxT+H/R.

Methods: Twenty four female Lewis rats (180-240g) were randomly divided into 3 groups: two groups underwent TxT followed by hemorrhagic shock (35±3mmHg) for 60min and resuscitation with either Ringers-Lactat (RL) alone or RL supplemented with EP (EP, 50mg/kg). Sham operated animals underwent surgical procedures. Two hours later bronchoalveolar lavage fluid (BAL), lung tissue and blood were collected for analyses.

Results: EP significantly improved pO2 levels compared to RL after TxT+H/R. TxT+H/R induced elevated levels of lactate dehydrogenase, total protein concentration in BAL and lung damage as evidenced by lung histology; these effects were significantly reduced by EP. Local inflammatory markers, lung TNF-alpha protein levels and infiltration with polymorphonuclear leukocytes (PMNL) significantly decreased in EP vs. RL group after TxT+H/R. Indicators of apoptosis as reduced BCL-2 and increased FAS gene expression after TxT+H/R were significantly increased or decreased, respectively, by EP after TxT+H/R. EP reduced TxT+H/R-induced p65 phosphorylation, which was concomitant with reduced HMGB1 levels in lung sections.

Conclusions: Taken together, TxT+H/R induced strong inflammatory response and apoptotic changes as well as lung injury which were markedly diminished by EP. Our results suggest that this might be mediated via NF-κB and/or HMGB1 dependent mechanism.

Keywords: Apoptosis; HMGB1; Lung; Necrosis; Neutrophils; Pyruvate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Disease Models, Animal
  • Gene Expression Regulation
  • HMGB1 Protein / metabolism
  • Humans
  • Lung / drug effects*
  • Lung / physiology
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Pyruvates / therapeutic use*
  • Rats
  • Rats, Inbred Lew
  • Shock, Hemorrhagic / diet therapy*
  • Signal Transduction / drug effects
  • Thoracic Injuries / drug therapy*
  • Tumor Necrosis Factor-alpha / metabolism


  • Anti-Inflammatory Agents
  • Bcl2 protein, rat
  • HMGB1 Protein
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • Pyruvates
  • Tumor Necrosis Factor-alpha
  • ethyl pyruvate