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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 
 Journal of Thoracic and Cardiovascular Surgery, Vol.155(4) : 1650-1658, 2018 
Journal Title
 Journal of Thoracic and Cardiovascular Surgery 
Issue Date
acute kidney injury ; ethyl pyruvate ; hyperglycemia ; ischemia-reperfusion
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-1beta, tumor necrosis factor-alpha, 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.
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1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
곽영란(Kwak, Young Lan) ORCID logo https://orcid.org/0000-0002-2984-9927
송종욱(Song, Jong Wook) ORCID logo https://orcid.org/0000-0001-7518-2070
심재광(Shim, Jae Kwang) ORCID logo https://orcid.org/0000-0001-9093-9692
최낙철(Choi, Nakcheol) ORCID logo https://orcid.org/0000-0002-1354-6366
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