Ethyl pyruvate is renoprotective against ischemia-reperfusion injury under hyperglycemia

Ji Hae Jun, Jong Wook Song, Eun Jung Shin, Young Lan Kwak, Nakcheol Choi, Jae Kwang Shim

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1650-1658
Number of pages9
JournalJournal of Thoracic and Cardiovascular Surgery
Volume155
Issue number4
DOIs
Publication statusPublished - 2018 Apr

All Science Journal Classification (ASJC) codes

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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