Water-soluble acacetin prodrug confers significant cardioprotection against ischemia/reperfusion injury
| Autor: | Feng Lin, Hui-Jun Wu, Hai-Ying Sun, Kui-Hao Chen, Gui-Rong Li, Lei Yang, Guo-Sheng Xiao, Hui Liu, Gang Li, Yan Wang |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Myocardial Infarction Ischemia Apoptosis Myocardial Reperfusion Injury 030204 cardiovascular system & hematology Pharmacology Protective Agents Models Biological Article Proinflammatory cytokine Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Thioredoxins 0302 clinical medicine Heart Rate In vivo Internal medicine Ventricular Pressure Animals Medicine Prodrugs cardiovascular diseases Cardioprotection Multidisciplinary Acacetin Interleukin-6 Superoxide Dismutase Tumor Necrosis Factor-alpha business.industry Myocardium Heart Prodrug Flavones medicine.disease Rats Toll-Like Receptor 4 Disease Models Animal Oxidative Stress 030104 developmental biology chemistry Cardiology business Reperfusion injury Ex vivo |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | The morbidity and mortality of patients with ischemic cardiomyopathy resulted from ischemia/reperfusion injury are very high. The present study investigates whether our previously synthesized water-soluble phosphate prodrug of acacetin was cardioprotective against ischemia/reperfusion injury in an in vivo rat model. We found that intravenous administration of acacetin prodrug (10 mg/kg) decreased the ventricular arrhythmia score and duration, reduced ventricular fibrillation and infarct size, and improved the impaired heart function induced by myocardial ischemia/reperfusion injury in anesthetized rats. The cardioprotective effects were further confirmed with the parent compound acacetin in an ex vivo rat regional ischemia/reperfusion heart model. Molecular mechanism analysis revealed that acacetin prevented the ischemia/reperfusion-induced reduction of the anti-oxidative proteins SOD-2 and thioredoxin, suppressed the release of inflammation cytokines TLR4, IL-6 and TNFα, and decreased myocyte apoptosis induced by ischemia/reperfusion. Our results demonstrate the novel evidence that acacetin prodrug confer significant in vivo cardioprotective effect against ischemia/reperfusion injury by preventing the reduction of endogenous anti-oxidants and the release of inflammatory cytokines, thereby inhibiting cardiomyocytes apoptosis, which suggests that the water-soluble acacetin prodrug is likely useful in the future as a new drug candidate for treating patients with acute coronary syndrome. |
| Databáze: | OpenAIRE |
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