Gas signaling molecule hydrogen sulfide attenuates doxorubicin-induced dilated cardiomyopathy

Abstract

Increasing evidence has revealed that hydrogen sulfide (H₂S) has beneficial effects in the treatment of various cardiovascular diseases. However, whether H₂S 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 H₂S 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 H₂S could improve left ventricular structure and function in DCM rats. H₂S was found to suppress doxorubicin-induced oxidative stress by activating the Nrf2 pathway and upregulating the expression of antioxidant proteins NQO1 and GCLM. Moreover, H₂S was also found to inhibit doxorubicin-induced cardiomyocyte apoptosis by activating the PI3K/Akt signaling pathway. In conclusion, our study demonstrates that H₂S protects against doxorubicin-induced DCM via attenuation of oxidative stress and apoptosis.