Autophagy protects against dasatinib-induced hepatotoxicity via p38 signaling

摘要: // Xiaochun Yang 1 , Jincheng Wang Jiabin Dai Jinjin Shao Jian Ma 2 Chao Chen Shenglin 3 Qiaojun He Peihua Luo and Bo Institute of Pharmacology & Toxicology, College Pharmaceutical Sciences, Zhejiang University, Hangzhou, China Center for Drug Safety Evaluation Research Nanjing Medical Affiliated Hangzhou Hospital, First People’s Correspondence: Luo, email: Yang, Keywords : Autophagy, p38 signaling, Hepatotoxicity, Dasatinib Received October 14, 2014 Accepted January 2015 Published 31, Abstract Liver dysfunction is a common side effect associated with the treatment dasatinib its mechanism poorly understood. Autophagy has been thought to be potent survival or death factor liver dysfunction, which may shed light on novel strategy intervention hepatotoxicity caused by dasatinib. In this study, we show first time that autophagy induced, consistent formation damage. inhibition exacerbated dasatinib-induced failure, suggesting acted as self-defense promote survival. Oxidative stress shown an important stimulus hepatotoxicity. Interestingly, increased activity p38, critical modulator oxidative related injury autophagy. silencing significantly blocked LC3-II induction p62 reduction dasatinib, was accompanied caspase-3 PARP cleavage, indicating alleviated via signaling. Finally, agonist isoproterenol hydrochloride (ISO) failure enhancing without affecting anticancer Thus, study revealed p38-activated promoted during injury, provide approaches managing clinical applications