Kyung Hye Lee1, Haneul Cho1, Sora Lee1, Jong Shin Woo1, Byung Hyun Cho1, Jung Hee Kang1, Yun-Mi Jeong1, Xian Wu Cheng1, Weon Kim2. 1. Division of Cardiology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea. 2. Division of Cardiology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea. Electronic address: mylovekw@hanmail.net.
Abstract
OBJECTIVES: Exenatide is a glucagon-like peptide-1 analogue that mitigates myocardial injury caused by ischemia-reperfusion injury via the survival signaling pathway. We hypothesized that exenatide would provide a protective effect in doxorubicin-induced cardiotoxicity. METHODS: H9c2 cardiomyocytes were pre-treated with exenatide followed by doxorubicin (DOX), and cell viability and intracellular reactive oxygen species (ROS) were subsequently measured. In order to determine the role of autophagy, we performed western blot as well as TUNEL and autophagosome staining. Additionally, rats were treated with exenatide 1h prior to every DOX treatment. Left ventricular (LV) function and performance were then assessed by echocardiography. Myocardial and serum ROS was measured with DHE fluorescence and ROS/RNS assay. RESULTS: DOX-induced caspase-3 activation decreased after pre-treatment with exenatide both in vivo and in vitro. Oxidative stress was attenuated by exenatide in H9c2 cells, as well as in cardiac tissue and serum. The number of autophagosomes and autophagic markers were further increased by exenatide in the DOX-treated H9c2 cells, which mediated AMPK activation. Suppression of the autophagosome abolished exenatide-induced anti-apoptotic effect. Echocardiography showed that pre-treatment with exenatide significantly improved LV dysfunction that is induced by DOX treatment. Exenatide inhibits the DOX-induced production of intracellular ROS and apoptosis in the myocardium. The autophagic markers increased in exenatide pre-treated cardiac tissue. CONCLUSION: Exenatide reduces DOX-induced apoptosis of cardiomyocytes by upregulating autophagy and improving cardiac dysfunction. These novel results highlight the therapeutic potential of exenatide to prevent doxorubicin cardiotoxicity. Copyright Â
OBJECTIVES:Exenatide is a glucagon-like peptide-1 analogue that mitigates myocardial injury caused by ischemia-reperfusion injury via the survival signaling pathway. We hypothesized that exenatide would provide a protective effect in doxorubicin-induced cardiotoxicity. METHODS: H9c2 cardiomyocytes were pre-treated with exenatide followed by doxorubicin (DOX), and cell viability and intracellular reactive oxygen species (ROS) were subsequently measured. In order to determine the role of autophagy, we performed western blot as well as TUNEL and autophagosome staining. Additionally, rats were treated with exenatide 1h prior to every DOX treatment. Left ventricular (LV) function and performance were then assessed by echocardiography. Myocardial and serum ROS was measured with DHE fluorescence and ROS/RNS assay. RESULTS:DOX-induced caspase-3 activation decreased after pre-treatment with exenatide both in vivo and in vitro. Oxidative stress was attenuated by exenatide in H9c2 cells, as well as in cardiac tissue and serum. The number of autophagosomes and autophagic markers were further increased by exenatide in the DOX-treated H9c2 cells, which mediated AMPK activation. Suppression of the autophagosome abolished exenatide-induced anti-apoptotic effect. Echocardiography showed that pre-treatment with exenatide significantly improved LV dysfunction that is induced by DOX treatment. Exenatide inhibits the DOX-induced production of intracellular ROS and apoptosis in the myocardium. The autophagic markers increased in exenatide pre-treated cardiac tissue. CONCLUSION:Exenatide reduces DOX-induced apoptosis of cardiomyocytes by upregulating autophagy and improving cardiac dysfunction. These novel results highlight the therapeutic potential of exenatide to prevent doxorubicincardiotoxicity. Copyright Â
Authors: Refaat A Eid; Mohammad Adnan Khalil; Mahmoud A Alkhateeb; Samy M Eleawa; Mohamed Samir Ahmed Zaki; Attalla Farag El-Kott; Mubarak Al-Shraim; Fahmy El-Sayed; Muhammad Alaa Eldeen; Mashael Mohammed Bin-Meferij; Khalid M E Awaji; Abdullah S Shatoor Journal: Cardiovasc Drugs Ther Date: 2021-12 Impact factor: 3.727
Authors: Refaat A Eid; Mashael Mohammed Bin-Meferij; Attalla Farag El-Kott; Samy M Eleawa; Mohamed Samir Ahmed Zaki; Mubarak Al-Shraim; Fahmy El-Sayed; Muhammad Alaa Eldeen; Mahmoud A Alkhateeb; Samah A Alharbi; Hussain Aldera; Mohammad A Khalil Journal: J Cardiovasc Transl Res Date: 2020-04-01 Impact factor: 4.132
Authors: Michael F Bode; Clare M Schmedes; Grant J Egnatz; Vanthana Bharathi; Yohei M Hisada; David Martinez; Tomohiro Kawano; Alice Weithauser; Leah Rosenfeldt; Ursula Rauch; Joseph S Palumbo; Silvio Antoniak; Nigel Mackman Journal: Sci Rep Date: 2021-07-12 Impact factor: 4.996