Cyclosporin A Protected Cardiomyocytes Against Oxidative Stress Injury by Inhibition of NF-B Signaling Pathway

PurposeThis study aims to investigate the effects and the molecular mechanism of cyclosporin A (CsA) against oxidative stress injury in cultured neonatal rat cardiomyocytes.MethodsBax/Bcl-2, cl-casp-9/casp-9, cl-casp-3/casp-3, and iNOS/-actin ratios and p-IB and IB levels were analyzed by western blot. IL-1 and TNF- levels were analyzed by ELISA.ResultsCsA 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-B was closely related to oxidative stress injury. CsA inhibited NF-B activation, thereby preventing the upregulation of IL-1, TNF-, iNOS, and intracellular NO release.ConclusionsCsA protected cardiomyocytes against H2O2-induced cell injury. Hence, CsA may be developed as a candidate drug to prevent or treat myocardial ischemia reperfusion injury.