Gas signaling molecule hydrogen sulfide attenuates doxorubicin-induced dilated cardiomyopathy

Increasing evidence has revealed that hydrogen sulfide (H(2)S) has beneficial effects in the treatment of various cardiovascular diseases. However, whether H(2)S can attenuate the development of dilated cardiomyopathy (DCM) remains unclear. In this study, we generated a rat model of DCM induced by doxorubicin and investigated the protective effects of H(2)S against DCM. Cardiac structure and function were analyzed by two-dimensional echocardiography. Oxidative stress was evaluated by measuring malondialdehyde, superoxide dismutase, glutathione peroxidase and reactive oxygen species. Cardiomyocyte apoptosis was assessed by flow cytometry following Annexin V/PI staining. Our results showed that exogenous administration of H(2)S could improve left ventricular structure and function in DCM rats. H(2)S was found to suppress doxorubicin-induced oxidative stress by activating the Nrf2 pathway and upregulating the expression of antioxidant proteins NQO1 and GCLM. Moreover, H(2)S was also found to inhibit doxorubicin-induced cardiomyocyte apoptosis by activating the PI3K/Akt signaling pathway. In conclusion, our study demonstrates that H(2)S protects against doxorubicin-induced DCM via attenuation of oxidative stress and apoptosis.