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Abstract

Resveratrol Inhibits Mitochondrial Apoptotic Response in Septic Cardiomyopathy via c-Jun NH2-Terminal Kinase/BAX/Cytochrome C Pathway

Author(s): Liang Lin, Guodong Cao, Youcheng Zeng, Yuhan Zhao and Qinghong Cheng*
Department of Cardiology, Shihezi University School of Medicine, 1Department of Critical Care Medicine II, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang Uyghur Autonomous Region 832000, China

Correspondence Address:
Qinghong Cheng, Department of Critical Care Medicine II, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang Uyghur Autonomous Region 832000, China, E-mail: Xunfeicheng@aliyun.com


A key factor in septic patient’s deaths is cardiac dysfunction brought on by sepsis. The molecular causes of septic cardiomyopathy and effective preventative treatments, however, remain unknown. Resveratrol is a naturally occurring antitoxin with several biological effects, including anticancer, a protective impact on the cardiovascular system, antiapoptotic, antioxidant, anti-free radical, antibacterial, antiviral, anti-inflammatory, and immunomodulatory. Whether resveratrol mediates bioactive resistance in septic myocardial damage is unknown, though. The c-Jun NH2-terminal kinase/Bcl-2-associated X protein/cytochrome C signaling pathway is involved in mitochondrial apoptosis. Activated c-Jun NH2-terminal kinase, or phospho-c-Jun NH2-terminal kinase, causes Bcl-2-associated X protein to move to the outer mitochondrial membrane, increasing its permeability, and later releases cytochrome C into the cytoplasm, initiating apoptosis. To decrease cardiac damage in sepsis, it was determined in this study if resveratrol mediates the apoptotic process of cardiomyocytes via the c-Jun NH2-terminal kinases/Bcl-2-associated X protein/cytochrome C signaling pathway. Rats with sepsis underwent cecum ligation puncture to cause myocardial damage, which was then treated with resveratrol. The outcomes demonstrated that resveratrol substantially reduced myocardial apoptosis, slowed reactive oxygen species generation, and ameliorated sepsis-induced cardiac dysfunction. The c-Jun NH2-terminal kinases/Bcl-2-associated X protein/cytochrome C pathway was shown to be much more agonistic in the H9c2 rat cardiomyocyte sepsis model than in the control group, although this was significantly decreased following treatment with resveratrol. We further demonstrated whether resveratrol mediates the c-Jun NH2-terminal kinase/Bcl-2-associated X protein/cytochrome C pathway by agonizing the c-Jun NH2-terminal kinase signaling pathway in vitro with a c-Jun NH2-terminal kinase-activator to increase sepsis-induced cardiac injury, while using resveratrol to verify its protective effect on myocardial injury in sepsis. All things considered, it has been established that resveratrol lessens myocardial cell death by controlling the c-Jun NH2-terminal kinase/Bcl-2-associated X protein/cytochrome C signaling pathway, thereby reducing the myocardial harm brought on by sepsis.

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