Role And Mechanism Of Exenatide On Adriamycin-induced Cardiac Injury

ObjectiveAdriamycin(ADR)is a very effective antineoplastic drug.Due to its fatal cardiac toxicity,its clinical application is greatly limited.At present,there are few studies about the effect of exenatide on cardiotoxicity induced by adriamycin.The purpose of this study is to explore the effect of exenatide on adriamycin-induced cardiotoxicity and its mechanism.MethodsMice were randomly divided into three groups:control group without intervention,adriamycin group 2 mg/kg through intraperitoneal injection,with a cumulative dose of 20 mg/kg,exenatide group 5 ug/kg through subcutaneous injection,one hour prior to adriamycin treatment.On the 20th day,left ventricular function was evaluated by echocardiography,tissue from plasma and heart were collected for further detection.H9c2 cells were cultured in DMEM medium.When the growth of H9c2 cells reached about 80%fusion,the cells were starved in serum-free DMEM medium for 24 hours.After treatment,the levels of reactive oxygen species(ROS),lactate dehydrogenase(LDH),creatine kinase MB(CK-MB),malondialdehyde(MDA),superoxide dismutase(SOD),tumor necrosis factor-A(TNF-a),interleukin-6(IL-6),caspase-3,caspase-9 and membrane potential were detected by kit.CCK-8,flow cytometry and TUNEL staining were used to detect the activity and apoptosis of cells,the mRNA expression of Bcl-2,Bax,TNF-a and IL-6 were detected by RT-PCR,and the protein expression of nuclear factor-kB(NF-kB)and p53 were detected by Western blot.ResultsCompared with control group,the cardiac function of mice in the adriamycin group was significantly impaired,plasma LDH,CK-MB and MDA levels were significantly increased,SOD activity were significantly decreased,cell activity was significantly decreased,intracellular ROS was significantly increased,Cytoplasm LDH,CK-MB,MDA,TNF-a,IL-6,caspase-3,caspase-9 levels were significantly increased,SOD levels and membrane potential were significantly decreased.Flow cytometry and TUNEL staining showed that the apoptotic rate of cardiomyocytes increased significantly,the mRNA expression of Bax,TNF-a and IL-6 increased significantly,while the expression of Bcl-2 decreased significantly.The protein expression of NF-kB and P53 increased significantly.Pretreatment with exenatide can significantly improved the results above.ConclusionExenatide can protect against adriamycin-induced cardiotoxicity by reducing oxidative stress,apoptosis and inflammation.