Hydrogen sulfide attenuates the development of diabetic cardiomyopathy

There is growing evidence that H₂S has beneficial effects in treatment of various cardiovascular diseases. However, it remains unclear whether H₂S can attenuate the development of diabetic cardiomyopathy (DCM). The present study was designed to investigate the protective effects of H₂S against DCM. Diabetic rats were induced by intraperitoneal injection of streptozotocin and administered with the H₂S donor sodium hydrosulfide (NaHS) for 16 weeks. Neonatal rat cardiomyocytes (NRCMs) transfected with nuclear factor erythroid 2-related factor 2 (Nrf2)-specific siRNA or pre-treated with SP600125, SB203580 or LY294002 prior to high glucose exposure were used to confirm the involvement of Nrf2/antioxidant response element (ARE), mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K)/Akt signalling pathways in the protective effects of H₂S. The echocardiographical and histopathological data indicated that H₂S improved left ventricular function and prevented cardiac hypertrophy and myocardial fibrosis in diabetic rats. H₂S was also found to attenuate hyperglycaemia-induced inflammation, oxidative stress and apoptosis in the cardiac tissue. In addition, H₂S could activate the Nrf2/ARE signalling pathway and up-regulate the expression of antioxidant proteins haem oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1) in the diabetic myocardium. Moreover, H₂S was found to reduce high glucose-induced apoptosis both in vitro and in vivo by inhibiting c-Jun N-terminal kinase (JNK) and p38 MAPK pathways and activating PI3K/Akt signalling. In conclusion, our study demonstrates that H₂S alleviates the development of DCM via attenuation of inflammation, oxidative stress and apoptosis.