Ethyl pyruvate is renoprotective against ischemia-reperfusion injury under hyperglycemia

J Thorac Cardiovasc Surg. 2018 Apr;155(4):1650-1658. doi: 10.1016/j.jtcvs.2017.10.069. Epub 2017 Nov 1.


Background: Hyperglycemia (HG) is common in cardiovascular surgeries due to diabetes, inflammation, and the neuroendocrine stress response. HG aggravates renal ischemia-reperfusion (I/R) injury through an increased inflammatory response, and blunts the protective effect of various measures. Ethyl pyruvate (EP) provides anti-inflammatory effects against I/R injury via inhibition of high-mobility group box 1 protein (HMGB1) release. This study aimed to determine the renoprotective effect of EP against I/R injury under HG.

Methods: Sprague-Dawley rats were randomly assigned at random to 8 groups: normoglycemia (NG)-sham, NG-I/R-control, NG-EP-I/R (pretreatment), NG-I/R-EP (posttreatment), HG-sham, HG-I/R-control, HG-EP-I/R, and HG-I/R-EP. Renal I/R was induced by 45 minutes of ischemia (clamping of renal arteries), followed by 24 hours of reperfusion. EP (50 mg/kg) was administered intraperitoneally at 1 h before ischemia (pretreatment) or on reperfusion (posttreatment).

Results: I/R injury under HG significantly aggravated the degree of renal tubular apoptosis and damage compared with the NG groups, which could be attenuated by both pretreatment and posttreatment of EP. I/R-induced increases in HMGB1 and Toll-like receptors (TLRs), activation of NF-kB, and resultant alterations in interleukin-1β, tumor necrosis factor-α, proapoptotic Bax, and antiapoptotic Bcl-2 were all favorably modulated by EP treatment in both the NG and HG groups compared with their corresponding control groups.

Conclusions: Despite aggravation of renal I/R injury by HG through amplified inflammation, EP administration showed similar suppression of the HMGB1-TLR-NF-kB pathway in the HG and NG groups. EP retained anti-inflammatory, antiapoptotic, and renoprotective effects in the HG groups, whether administered before ischemia or on reperfusion.

Keywords: acute kidney injury; ethyl pyruvate; hyperglycemia; ischemia-reperfusion.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis / drug effects
  • Blood Glucose / metabolism*
  • Cytoprotection
  • Disease Models, Animal
  • HMGB1 Protein / metabolism
  • Hyperglycemia / blood
  • Hyperglycemia / complications
  • Hyperglycemia / drug therapy*
  • Interleukin-1beta / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / etiology
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control*
  • Male
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Pyruvates / pharmacology*
  • Rats, Sprague-Dawley
  • Reperfusion Injury / etiology
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Signal Transduction / drug effects
  • Toll-Like Receptors / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • bcl-2-Associated X Protein / metabolism


  • Anti-Inflammatory Agents
  • Bax protein, rat
  • Bcl2 protein, rat
  • Blood Glucose
  • HMGB1 Protein
  • Hbp1 protein, rat
  • IL1B protein, rat
  • Interleukin-1beta
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • Pyruvates
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • ethyl pyruvate