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 language | English |
|---|---|
| Pages (from-to) | 1650-1658 |
| Number of pages | 9 |
| Journal | Journal of Thoracic and Cardiovascular Surgery |
| Volume | 155 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2018 Apr |
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All Science Journal Classification (ASJC) codes
- Surgery
- Pulmonary and Respiratory Medicine
- Cardiology and Cardiovascular Medicine
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Ethyl pyruvate is renoprotective against ischemia-reperfusion injury under hyperglycemia. / Jun, Ji Hae; Song, Jong Wook; Shin, Eun Jung; Kwak, Young Lan; Choi, Nakcheol; Shim, Jae Kwang.
In: Journal of Thoracic and Cardiovascular Surgery, Vol. 155, No. 4, 04.2018, p. 1650-1658.Research output: Contribution to journal › Article
TY - JOUR
T1 - Ethyl pyruvate is renoprotective against ischemia-reperfusion injury under hyperglycemia
AU - Jun, Ji Hae
AU - Song, Jong Wook
AU - Shin, Eun Jung
AU - Kwak, Young Lan
AU - Choi, Nakcheol
AU - Shim, Jae Kwang
PY - 2018/4
Y1 - 2018/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85035202718&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85035202718&partnerID=8YFLogxK
U2 - 10.1016/j.jtcvs.2017.10.069
DO - 10.1016/j.jtcvs.2017.10.069
M3 - Article
C2 - 29195627
AN - SCOPUS:85035202718
VL - 155
SP - 1650
EP - 1658
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
SN - 0022-5223
IS - 4
ER -