Chung-Lin Tsai1,2, Chia-Wen Tsai1,3, Wen-Shin Chang1,3, Jiunn-Cherng Lin4, Liang-Chun Shih1,3, Jie-Long He5, DA-Tian Bau6,3,7. 1. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C. 2. Division of Cardiac and Vascular Surgery, Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C. 3. Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C. 4. Division of Cardiology, Department of Internal Medicine, Taichung Veterans General Hospital Chiayi Branch, Chiayi, Taiwan, R.O.C. 5. Department of Post-Baccalaureate Veterinary Medicine, Asia University, Taichung, Taiwan, R.O.C. 6. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C.; datian@mail.cmuh.org.tw artbau2@gmail.com. 7. Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan, R.O.C.
Abstract
BACKGROUND/AIM: The clinical use of arsenic trioxide (As2O3) is hampered due to its cardiotoxicity. Therefore, it is critical to prevent As2O3-induced loss of endothelial integrity. The purpose of this study was to examine As2O3-induced endothelial dysfunction and evaluate the efficacy of crocetin on reversing As2O3-induced cardiotoxicity. MATERIALS AND METHODS: Cultured human umbilical vein endothelial cells (HUVECs) were used to examine As2O3-induced oxidative stress, apoptosis, production of reactive oxygen species (ROS) and DNA adducts. In addition, the impact of crocetin on As2O3-induced cardiotoxicity was evaluated. RESULTS: As2O3 decreased the viability of HUVEC cells and led to apoptosis. Additionally, As2O3 elevated NADPH oxidase activity, and the levels of intracellular ROS. Furthermore, the formamidopyrimidine DNA-glycosylase- and endonuclease III-digestible adducts were induced by As2O3 Crocetin treatment reversed the As2O3-induced reduction in cell viability, the induction of apoptosis, the activation of NADPH oxidase activity, ROS levels and DNA adducts. CONCLUSION: Crocetin protects from As2O3-induced cardio-toxicity.
BACKGROUND/AIM: The clinical use of arsenic trioxide (As2O3) is hampered due to its cardiotoxicity. Therefore, it is critical to prevent As2O3-induced loss of endothelial integrity. The purpose of this study was to examine As2O3-induced endothelial dysfunction and evaluate the efficacy of crocetin on reversing As2O3-induced cardiotoxicity. MATERIALS AND METHODS: Cultured human umbilical vein endothelial cells (HUVECs) were used to examine As2O3-induced oxidative stress, apoptosis, production of reactive oxygen species (ROS) and DNA adducts. In addition, the impact of crocetin on As2O3-induced cardiotoxicity was evaluated. RESULTS: As2O3 decreased the viability of HUVEC cells and led to apoptosis. Additionally, As2O3 elevated NADPH oxidase activity, and the levels of intracellular ROS. Furthermore, the formamidopyrimidine DNA-glycosylase- and endonuclease III-digestible adducts were induced by As2O3 Crocetin treatment reversed the As2O3-induced reduction in cell viability, the induction of apoptosis, the activation of NADPH oxidase activity, ROS levels and DNA adducts. CONCLUSION: Crocetin protects from As2O3-induced cardio-toxicity.
Authors: Katherine A Moon; Eliseo Guallar; Jason G Umans; Richard B Devereux; Lyle G Best; Kevin A Francesconi; Walter Goessler; Jonathan Pollak; Ellen K Silbergeld; Barbara V Howard; Ana Navas-Acien Journal: Ann Intern Med Date: 2013-11-19 Impact factor: 25.391