1. Academic Validation
  2. Exenatide alleviates adriamycin-induced heart dysfunction in mice: Modulation of oxidative stress, apoptosis and inflammation

Exenatide alleviates adriamycin-induced heart dysfunction in mice: Modulation of oxidative stress, apoptosis and inflammation

  • Chem Biol Interact. 2019 May 1;304:186-193. doi: 10.1016/j.cbi.2019.03.012.
Juntao Fang 1 Yida Tang 2 Xianwu Cheng 3 Lijuan Wang 1 Can Cai 1 Xiaoman Zhang 1 Shangyu Liu 1 Ping Li 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
  • 2 State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China; Department of Cardiology, The Endocrinology and CardioMetabolic Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences, Peking Union Medical College, 167 Beilishi Rd, Xicheng District, Beijing, 100037, China.
  • 3 The Department of Cardiology and Hypertension, Yanbian University Hospital, Yanji, 133000, China.
  • 4 State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China; Department of Cardiology, The Endocrinology and CardioMetabolic Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences, Peking Union Medical College, 167 Beilishi Rd, Xicheng District, Beijing, 100037, China. Electronic address: liping@fuwaihospital.org.
Abstract

Background: Adriamycin (ADR) is an effective antineoplastic drug; the clinical application of ADR is limited due to fatal heart dysfunction. Exenatide has antioxidant, anti-apoptotic and anti-inflammatory properties. It can alleviate heart damage induced by ischaemia-reperfusion injury. Thus, we assumed that exenatide would produce protective effects on ADR-induced heart dysfunction.

Method: Mice were treated with exenatide 1 h prior to every ADR treatment for 20 days. Left ventricular function and performance were assessed by echocardiography. Additionally, H9c2 cells were pretreated with exenatide followed by ADR, and intracellular Reactive Oxygen Species (ROS) and cell viability, as well as the Lactate Dehydrogenase (LDH) and the creatine kinase MB (CK-MB), were subsequently measured. Flow cytometry and TUNEL staining were applied to assess the effect of exenatide on cardiac damage caused by ADR. Western blot and RT-PCR were performed to detect the effect of exenatide on apoptosis-related genes (Bcl-2 and Bax) and inflammation-related genes and/or proteins (tumour necrosis factor-α, interleukin-6, nuclear factor-κB, and p53).

Result: Echocardiography showed that cardiac dysfunction caused by ADR was significantly improved by treatment with exenatide. ADR mice had harmful changes in the levels of ROS and CK-MB/LDH production, as well as the targeted apoptotic and inflammatory molecules, and these effects were also reversed by exenatide. In vitro, exenatide mitigated ADR-induced oxidative stress and CK-MB/LDH production, as well as Annexin V+/PI+ and TUNEL+ Apoptosis in H9c2 cells.

Conclusion: In conclusion, our research demonstrated the potential protective effects of exenatide on ADR-induced heart dysfunction through suppressing oxidative stress, Apoptosis and inflammation.

Keywords

Adriamycin; Apoptosis; Exenatide; Heart dysfunction; Inflammation; Oxidative stress.

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