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Protective Effect of Ethyl Pyruvate against Myocardial Ischemia Reperfusion Injury through Regulations of ROS-Related NLRP3 Inflammasome Activation

Authors
 Ji Hae Jun  ;  Jae-Kwang Shim  ;  Ju Eun Oh  ;  Eun-Jung Shin  ;  Eunah Shin  ;  Young-Lan Kwak 
Citation
 OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, Vol.2019 : 4264580, 2019 
Journal Title
 OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 
ISSN
 1942-0900 
Issue Date
2019
MeSH
Animals ; Humans ; Inflammasomes/metabolism* ; Male ; Myocardial Reperfusion Injury/drug therapy* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pyruvates/pharmacology ; Pyruvates/therapeutic use* ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species
Abstract
Emerging evidence indicates the pronounced role of inflammasome activation linked to reactive oxygen species (ROS) in the sterile inflammatory response triggered by ischemia/reperfusion (I/R) injury. Ethyl pyruvate (EP) is an antioxidant and conveys myocardial protection against I/R injury, while the exact mechanisms remain elusive. We aimed to investigate the effect of EP on myocardial I/R injury through mechanisms related to ROS and inflammasome regulation. The rats were randomly assigned to four groups: (1) sham, (2) I/R-control (IRC), (3) EP-pretreatment + I/R, and (4) I/R + EP-posttreatment. I/R was induced by a 30 min ligation of the left anterior descending artery followed by 4 h of reperfusion. EP (50 mg/kg) was administered intraperitoneally at 1 h before ischemia (pretreatment) or upon reperfusion (posttreatment). Both pre- and post-EP treatment resulted in significant reductions in myocardial infarct size (by 34% and 31%, respectively) and neutrophil infiltration. I/R-induced myocardial expressions of NADPH oxidase-4, carnitine palmitoyltransferase 1A, and thioredoxin-interacting protein (TXNIP) were mitigated by EP. EP treatment was associated with diminished inflammasome activation (NOD-like receptor 3 (NLRP3), apoptosis-associated speck-like protein, and caspase-1) and interleukin-1β induced by I/R. I/R-induced phosphorylation of ERK and p38 were also mitigated with EP treatments. In H9c2 cells, hypoxia-induced TXNIP and NLRP3 expressions were inhibited by EP and to a lesser degree by U0126 (MEK inhibitor) and SB203580 (p38 inhibitor) as well. EP's downstream protective mechanisms in myocardial I/R injury would include mitigation of ROS-mediated NLRP3 inflammasome upregulation and its associated pathways, partly via inhibition of hypoxia-induced phosphorylation of ERK and p38.
Files in This Item:
T201904519.pdf Download
DOI
10.1155/2019/4264580
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
Kwak, Young Lan(곽영란) ORCID logo https://orcid.org/0000-0002-2984-9927
Shim, Jae Kwang(심재광) ORCID logo https://orcid.org/0000-0001-9093-9692
Oh, Ju Eun(오주은)
Jun, Ji Hae(전지혜) ORCID logo https://orcid.org/0000-0002-8080-0715
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/173344
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