Cyclosporin A Protected Cardiomyocytes Against Oxidative Stress Injury by Inhibition of NF-κB Signaling Pathway
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This study aims to investigate the effects and the molecular mechanism of cyclosporin A (CsA) against oxidative stress injury in cultured neonatal rat cardiomyocytes.
Bax/Bcl-2, cl-casp-9/casp-9, cl-casp-3/casp-3, and iNOS/β-actin ratios and p-IκB and IκB levels were analyzed by western blot. IL-1β and TNF-α levels were analyzed by ELISA.
CsA effectively improved the cell viability and reduced the extracellular lactate dehydrogenase release in cardiomyocytes after H2O2-induced oxidative damage. CsA significantly increased the superoxide dismutase activity, glutathione production, and catalase activity but decreased the malonaldehyde level. CsA treatment considerably reduced the H2O2-induced intracellular generation of reactive oxygen species, mitochondrial dysfunction, and release of cytochrome c. CsA could act against H2O2-induced ATP reduction, TCA cycle enzymes, mitochondrial complex I enzyme, and complex V enzyme in cardiomyocytes. CsA significantly decreased the Bax/Bcl-2 ratio, cl-casp-9/casp-9, and cl-casp-3/casp-3 in a concentration-dependent manner. CsA also remarkably reduced the cleaved PARP level and DNA fragmentation. NF-κB was closely related to oxidative stress injury. CsA inhibited NF-κB activation, thereby preventing the upregulation of IL-1β, TNF-α, iNOS, and intracellular NO release.
CsA protected cardiomyocytes against H2O2-induced cell injury. Hence, CsA may be developed as a candidate drug to prevent or treat myocardial ischemia reperfusion injury.
KeywordsCsA Cardiomyocytes H2O2 Oxidative stress NF-κB
This study was funded by Shandong health science and technology association (No. 2017BJ007).
Conflict of interest
Author Meng Ma declares that he has no conflict of interest. Author Xiaohui Ma declares that she has no conflict of interest. Author Jie Cui declares that she has no conflict of interest. Author Yifeng Guo declares that she has no conflict of interest. Author Xiuqin Tang declares that she has no conflict of interest. Author Chuanmin Chen declares that he has no conflict of interest. Author Ying Zhu declares that she has no conflict of interest. Author Chao Cui declares that she has no conflict of interest. Author Gang Wang declares that he has no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
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