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Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):395-399. doi: 10.1016/j.bbrc.2018.11.049. Epub 2018 Nov 13.

Cardioprotective effect of levosimendan against homocysteine-induced mitochondrial stress and apoptotic cell death in H9C2.

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Department of Pharmacology and Toxicology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran; Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran. Electronic address:
Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.


Levosimendan is a cardiac inotropic and vasodilator agent that has been reported to have anti-oxidative, anti-inflammatory, and smooth muscle vasodilatory properties. The purpose of this study was to examine the effect of levosimendan on homocysteine-induced cardiomyocyte injury and to explore its underlying mechanisms. H9C2 myocardial cells were incubated with levosimendan 30 min before exposure to homocysteine (Hcy) for 24 h. The effect of levosimendan on cell viability was assessed using the MTT assay. Biological markers of oxidative stress were examined by assessment of lipid peroxidation (LPO), total antioxidant power (TAP), and total thiol groups. Moreover, the expression of caspase-3, Bcl-2, and Bax proteins was determined by western blot analysis. These results showed that levosimendan increased survival of cardiomyocytes in Hcy condition. Treatment with levosimendan decreased lipid peroxidation level. It also enhanced the TAP and total thiol groups. Further, levosimendan pretreatment upregulated the expression of Bcl-2 and downregulated the expression of Bax. The experiments also demonstrated that levosimendan could decrease the expression and activity of caspase-3, which is a key factor in regulating apoptosis. Taken together, these results indicated that levosimendan protects H9C2 myocardial cells against Hcy-induced oxidative stress and apoptosis by scavenging free radicals and modulating the mitochondrial-mediated apoptotic signaling pathway.


Apoptosis; H9C2 cells; Homocysteine; Levosimendan; Oxidative stress

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