Effects of edaravone in heart of aged rats after cerebral ischemia-reperfusion injury.
Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has potent effects in the brain as a free radical scavenger in ischemia-reperfusion (IR) injuries. However, whether this free radical scavenger can prevent myocardial injury after cerebral IR is not clear. The aim of the present study was to investigate the effect of edaravone against oxidative damage in brain-to-heart signaling triggered by IR injury and its possible mechanism. In this study, the expression of glutathione peroxidase (GSHPx) and protein carbonyl content was examined to evaluate oxidative stress. The activation of mitogen-activated protein kinases (MAPKs) was also examined. Terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) analysis was performed to estimate cardiomyocytes cell death. After edaravone treatment there was a mild increase in activities of GSHPx in cardiomyocytes; however, there was a decrease in protein carbonyl content. p38 MAPK activity was inhibited by edaravone treatment in comparison with the vehicle group in myocardium. These results were further complemented by a significant reduction of TUNEL-positive cells in the heart sections. Our results demonstrate that edaravone provides ameliorative effects in the myocardium after cerebral IR injury by differentially modulating MAPK's activity, thus reducing the oxidative stress state.
Watanabe
Kenichi
K
Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima, Niigata 956-8603, Japan. watanbe@niigata-pharm.ac.jp
Ma
Meilei
M
Wen
Juan
J
Kodama
Makoto
M
Aizawa
Yoshifusa
Y
D000375:Aging; D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002545:Brain Ischemia / Q000150:complications; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D000077553:Edaravone; D004797:Enzyme-Linked Immunosorbent Assay; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D006335:Heart Injuries / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D020287:In Situ Nick-End Labeling / Q000379:methods; D007275:Injections, Intravenous; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D016166:Free Radical Scavengers; D005979:Glutathione Peroxidase; D048051:p38 Mitogen-Activated Protein Kinases; D000077553:Edaravone; D000983:Antipyrine