Adenylyl cyclase 1 mitigates doxorubicin-induced cardiotoxicity by reducing oxidative stress and myocardial damage

¹ Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
² Physical Examination Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
³ Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, China
⁴ Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

^* Corresponding author: Qingwen Zhang, zhangqw@sumhs.edu.cn Yanfei Li, liyf@sumhs.edu.cn.

Abstract

Doxorubicin (DOX), a commonly used ant-cancer drug, has its clinical application severely restricted due to its serious cardiotoxic side-effects. Adenylyl cyclase 1 (ADCY1) is recognized for its pivotal role in cardiac pathophysiology. Nonetheless, the involvement of ADCY1 in DOX-induced cardiotoxicity (DIC) remains not well-studied. This study aimed to elucidate the role of ADCY1 in DIC, in particular whether ADCY1 affects oxidative stress and myocardial injury. Our findings indicate that ADCY1 expression is downregulated in DOX-treatment AC16 cardiomyocytes with a DOX concentration- dependent manner. Silencing of ADCY1 further exacerbated DIC. It was manifested by the elevated levels of ANP, BNP, LDH oxidative stress compared with DOX treatment group. Conversely, over expression of ADCY1 mitigated these adverse effects induced by DOX. Our study elucidates the cardioprotective effects of ADCY1 by attenuating DOX-induced myocardial injury, oxidative stress . It provides a novel perspective for the development of therapeutic strategies aimed at reducing cardiac toxicity in patients undergoing DOX treatment.