Endogenous sulfur dioxide protects against isoproterenol-induced myocardial injury and increases myocardial antioxidant capacity in rats

Recently, sulfur dioxide (SO2) was discovered to be produced in the cardiovascular system and to influence important biological processes. Here, we investigated changes in endogenous SO2/glutamic oxaloacetic transaminase (GOT) pathway in the development of isoproterenol (ISO)-induced myocardial injury in rats and the regulatory effect of SO2 on cardiac function, myocardial micro-and ultrastructure, and oxidative stress. Wistar male rats were divided into control, ISO-treated, ISO+SO2, and SO2 groups. At the termination of the experiment, parameters of cardiac function and hemodynamics were measured and the micro-and ultrastructure of myocardium and stereological ultrastructure of mitochondria were analyzed. Myocardial SO2 content was detected by high-performance liquid chromatography. GOT (key enzyme for endogenous SO2 production) activity and gene (GOT1 and GOT2) expressions were measured, and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), hydrogen peroxide, and superoxide radical levels were assayed. SOD (SOD1 and SOD2) and GSH-Px (GSH-Px1) gene expressions were also detected. The results showed that SO2 donor at a dose of 85 mg/(kg day) did not impact the cardiac function and structure of rats, but exerted a subtle influence on myocardial redox status. ISO-treated rats exhibited decreased cardiac function, damaged myocardial structures, and downregulated endogenous SO2/GOT pathway. Meanwhile, myocardial oxidative stress increased, whereas antioxidative capacity downregulated. Administration of SO2 markedly improved cardiac function and ISO-induced myocardial damage by ameliorating the pathological structure of the myocardium and the mitochondria. At the same time, myocardial products of oxidative stress decreased, whereas antioxidative capacity increased. These results suggest that downregulation of the endogenous SO2/GOT pathway is likely involved in the pathogenesis of ISO-induced myocardial injury. SO2 protects against ISO-induced myocardial injury associated with increased myocardial antioxidant capacity in rats. Laboratory Investigation (2011) 91, 12-23; doi:10.1038/labinvest.2010.156; published online 23 August 2010