Sodium hydrosulfide attenuates hyperhomocysteinemia rat myocardial injury through cardiac mitochondrial protection

• Published in: Molecular and cellular biochemistry 2015-01, Vol.399 (1-2), p.189-200
• Main Authors: Wang, Yuwen, Shi, Sa, Dong, Shiyun, Wu, Jichao, Song, Mowei, Zhong, Xin, Liu, Yanhong
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Biochemistry; Biomedical and Life Sciences; Cardiology; Cardiotonic Agents - pharmacology; Cells, Cultured; Drug Evaluation, Preclinical; Heart Diseases - prevention & control; Hydrogen sulfide; Hyperhomocysteinemia - complications; Hyperhomocysteinemia - drug therapy; Life Sciences; Male; Medical Biochemistry; Membrane Potential, Mitochondrial - drug effects; Mitochondria, Heart - drug effects; Mitochondria, Heart - metabolism; Mitochondrial DNA; Myocardium - pathology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - physiology; Nitric oxide; Oncology; Rats, Wistar; Reactive Oxygen Species - metabolism; Sulfides - pharmacology
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-014-2245-6

Hydrogen sulfide (H 2 S) plays an important role during rat myocardial injury. However, little is known about the role of H 2 S in hyperhomocysteinemia (HHcy)-induced cardiac dysfunction as well as the underlying mechanisms. In this study, we investigated whether sodium hydrosulfide (NaHS, a H 2 S donor) influences methionine-induced HHcy rat myocardial injury in intact rat hearts and primary neonatal rat cardiomyocytes. HHcy rats were induced by methionine (2.0 g/kg) and the daily administration of 80 μmol/L NaHS in the HHcy + NaHS treatment group. At the end of 4, 8, and 12 weeks, the ultrastructural alterations and functions of the hearts were observed using transmission electron microscopy and echocardiography system. The percentage of apoptotic cardiomyocytes, the mitochondrial membrane potential, and the production of reactive oxygen species (ROS) were measured. The expressions of cystathionine-γ-lyase (CSE), Bax and Bcl-2, caspase-3, phospho-endothelial nitric oxide synthase and the mitochondrial NOX4 and cytochrome c were analyzed by Western blotting. The results showed the cardiac dysfunction, the ultrastructural changes, and the apoptotic rate increase in the HHcy rat hearts. In the primary neonatal rat cardiomyocytes of HHcy group, ROS production was increased markedly, whereas the expression of CSE was decreased. However, treatment with NaHS significantly improved the HHcy rat hearts function, the ultrastructural changes, and decreased the levels of ROS in the primary neonatal rat cardiomyocytes administrated with HHcy group. Furthermore, NaHS down-regulated the expression of mitochondrial NOX4 and caspase-3 and Bax and inhibited the release of cytochrome c from mitochondria. In conclusion, H 2 S is involved in the attenuation of HHcy myocardial injury through the protection of cardiac mitochondria.