Ji Hae Jun1, Jong Wook Song2, Eun-Jung Shin1, Young-Lan Kwak2, Nakcheol Choi3, Jae-Kwang Shim4. 1. Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea. 2. Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. 3. Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. 4. Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: aneshim@yuhs.ac.
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.
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.