Gas signaling molecule hydrogen sulfide attenuates doxorubicin-induced dilated cardiomyopathy

// Zongliang Yu 1, * , Wei Zhang 2, * , Mengyao Zhang 1, * , Mengchao Jin 2 , Weiting Xu 2 and Xiang Zhou 2 1 Department of Cardiology, The First People's Hospital of Kunshan Affiliated to Jiangsu University, Kunshan, China 2 Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, China * These authors have contributed equally to this work Correspondence to: Xiang Zhou, email: zhou-xiang@suda.edu.cn Keywords: hydrogen sulfide, doxorubicin, dilated cardiomyopathy, oxidative stress, apoptosis Received: June 26, 2017 Accepted: August 09, 2017 Published: September 08, 2017 ABSTRACT 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.