Salvianolic Acid A Protects H9c2 Cells from Arsenic Trioxide-Induced Injury via Inhibition of the MAPK Signaling Pathway

• Main Authors: Jing-yi Zhang, Gui-bo Sun, Yun Luo, Min Wang, Wei Wang, Yu-yang Du, Ying-li Yu, Xiao-bo Sun
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2017-04-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Arsenic trioxide; Salvianolic acid A; Cardiotoxicity; Apoptosis; Oxidative stress; MAPK
• Online Access: http://www.karger.com/Article/FullText/472409

Background/Aims: This study aimed to investigate whether Salvianolic acid A (Sal A) conferred cardiac protection against Arsenic trioxide (ATO)-induced cardiotoxicity in H9c2 cells by inhibiting MAPK pathways activation. Methods: H9c2 cardiac cells were exposed to 10 µM ATO for 24 h to induce cytotoxicity. The cells were pretreated with Sal A for 4 h before exposure to ATO. Cell viability was determined utilizing the MTT assay. The percentage of apoptosis was measured by a FITC-Annexin V/PI apoptosis kit for flow cytometry. Mitochondrial membrane potential (∆Ψm) was detected by JC-1. The intracellular ROS levels were measured using an Image-iTTM LIVE Green Reactive Oxygen Species Detection Kit. The apoptosis-related proteins and the MAPK signaling pathways proteins expression were quantified by Western blotting. Results: Sal A pretreatment increased cell viability, suppressed ATO-induced mitochondrial membrane depolarization, and significantly altered the apoptotic rate by enhancing endogenous antioxidative enzyme activity and ROS generation. Signal transduction studies indicated that Sal A suppressed the ATO-induced activation of the MAPK pathway. More importantly, JNK, ERK, and p38 inhibitors mimicked the cytoprotective activity of Sal A against ATO-induced injury in H9c2 cells by increasing cell viability, up-regulating Bcl-2 protein expression, and down-regulating both Bax and caspase-3 protein expression. Conclusion: Sal A decreases the ATO-induced apoptosis and necrosis of H9c2 cells, and the underlying mechanisms of this protective effect of Sal A may be connected with the MAPK pathways.