Carvedilol prevents doxorubicin-induced free radical release and apoptosis in cardiomyocytes in vitro

Journal of Molecular and Cellular Cardiology
Paolo SpallarossaClaudio Brunelli

Abstract

The clinical use of doxorubicin, a highly active anticancer drug, is limited by its severe cardiotoxic side effects. Increased oxidative stress and apoptosis have been implicated in the cardiotoxicity of doxorubicin. Carvedilol is an adrenergic blocking agent with potent anti-oxidant activity. In this study we investigated whether carvedilol has protective effects against doxorubicin-induced free radical production and apoptosis in cultured cardiac muscle cells, and we compared the effects of carvedilol to atenolol, a beta-blocker with no anti-oxidant activity. Reactive oxygen species (ROS) generation in cultured cardiac muscle cells (H9c2 cells) was evaluated by flow cytometry using dichlorofluorescein (DCF) and hydroethidine (HE). Apoptosis was assessed by measuring annexin V-FITC/propidium iodide double staining, DNA laddering, levels of expression of the pro-apoptotic protein Bax-alpha and the anti-apoptotic protein Bcl-2, and caspase-3 activity. Pre-treatment with carvedilol significantly attenuated the doxorubicin-induced increases in DCF (P < 0.001 compared to cells not pre-treated with carvedilol) and HE (P < 0.01) fluorescence. Doxorubicin increased the fraction of annexin V-FITC-positive fluorescent cells, while pre-t...Continue Reading

References

Jan 1, 1985·Heart and Vessels. Supplement·V J Ferrans, J F Van Vleet
Oct 1, 1981·American Heart Journal·M R BristowJ R Daniels
Nov 16, 1995·The New England Journal of Medicine·D L Fenster
Jan 1, 1994·Cold Spring Harbor Symposia on Quantitative Biology·A H WyllieR G Morris
Feb 1, 1994·Free Radical Biology & Medicine·N W KooyJ S Beckman
Apr 1, 1994·Free Radical Biology & Medicine·P Ubezio, F Civoli
Jan 1, 1996·Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology·J LekakisS Moulopoulos
Jul 17, 1998·Transplant International : Official Journal of the European Society for Organ Transplantation·S ShintakuK Dohi
Oct 28, 1998·Clinical Cardiology·S FazioL Saccà
Nov 21, 1998·Free Radical Biology & Medicine·L BenovI Fridovich
Dec 10, 1998·The New England Journal of Medicine·W H Frishman
Feb 19, 1999·Circulation Research·D B SawyerR A Kelly
Jul 23, 1999·Annals of the New York Academy of Sciences·D KumarP Singal
Mar 31, 2000·Experimental Cell Research·B Antonsson, J C Martinou
May 19, 2000·Breast Cancer Research and Treatment·A MichelottiP Conte
Jun 30, 2000·Current Opinion in Cell Biology·M Crompton
Jul 25, 2000·Journal of Cardiac Failure·A NooriB D Lowes
Sep 26, 2000·Molecular Genetics and Metabolism·M S HorensteinT J L'Ecuyer
Apr 9, 2001·Antioxidants & Redox Signaling·D KumarP K Singal
Jan 17, 2002·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Sharon Phaneuf, Christiaan Leeuwenburgh
Jun 14, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Xuwan LiuBalvin H L Chua
Oct 16, 2002·Biochimica Et Biophysica Acta·Pattie S Green, Christiaan Leeuwenburgh
Dec 31, 2002·Journal of Molecular and Cellular Cardiology·Semon WuYing-Shiung Lee
Jan 1, 2003·Human & Experimental Toxicology·T K YeungJ W Hopewell
Mar 12, 2003·Journal of the American College of Cardiology·Satoshi YamanakaMasao Nakagawa
Apr 4, 2003·Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology·Isao MitaniBarry L Zaret
Aug 19, 2007·Seminars in Oncology Nursing·William P Hogle
Feb 6, 2008·Basic & Clinical Pharmacology & Toxicology·Bulent KaragozE Gokhan Kandemir

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Citations

Dec 25, 2012·Future Cardiology·Alessandro Colombo, Daniela Cardinale
Aug 9, 2012·Future Cardiology·Danielle HarakeSteven E Lipshultz
May 13, 2014·Current Treatment Options in Cardiovascular Medicine·Laura Carola MagnanoXavier Bosch
Apr 29, 2014·Current Treatment Options in Cardiovascular Medicine·Alessandro ColomboDaniela Cardinale
Aug 16, 2006·Journal of Zhejiang University. Science. B·He HuangLing-bo Qian
Oct 30, 2009·Archivum Immunologiae Et Therapiae Experimentalis·Yi-Wei ZhangLei Wei
Apr 5, 2011·Antioxidants & Redox Signaling·Laura A A Gilliam, Daret K St Clair
Sep 30, 2006·Cell Biology and Toxicology·J M Berthiaume, K B Wallace
Nov 26, 2008·Current Treatment Options in Cardiovascular Medicine·Daniela CardinaleCarlo Maria Cipolla
May 17, 2013·Current Treatment Options in Cardiovascular Medicine·Alessandro ColomboDaniela Cardinale
May 18, 2011·Cellular and Molecular Life Sciences : CMLS·Katherine VerverisTom C Karagiannis
Mar 21, 2013·Current Cardiology Reports·Alessandro ColomboDaniela Cardinale
Jan 4, 2008·Heart Failure Reviews·Eloisa ArbustiniJagat Narula
May 17, 2008·Apoptosis : an International Journal on Programmed Cell Death·Ching-Feng ChengHeng Lin
Oct 6, 2007·Naunyn-Schmiedeberg's Archives of Pharmacology·Jin-Shiung ChengChung-Ren Jan
Jan 12, 2011·Pediatric Cardiology·Barry H TrachtenbergSteven E Lipshultz
Oct 10, 2007·Cardiovascular Drugs and Therapy·Xing ChenJing Xu
Apr 18, 2015·Drug and Chemical Toxicology·Nathalie ChahineRamez Chahine
May 31, 2011·Journal of Receptor and Signal Transduction Research·Yao-Dung HsiehChung-Ren Jan
Mar 30, 2012·Toxicology Mechanisms and Methods·Yong-Hyun KimWan-Joo Shim
Jun 1, 2011·Journal of Molecular and Cellular Cardiology·Geert C van AlmenStephane Heymans
Sep 24, 2009·Mitochondrion·M A Carvalho RodriguesA C Santos
Aug 25, 2009·Biochemical and Biophysical Research Communications·Mylène GilleronSteve Lancel
Jan 19, 2008·Translational Research : the Journal of Laboratory and Clinical Medicine·Jie GaoPeiqing Liu
Mar 17, 2007·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Eun-Jung Park, Kwangsik Park
Aug 30, 2008·Journal of Cellular and Molecular Medicine·Elisabetta BorchiChiara Nediani
Dec 15, 2005·British Journal of Haematology·Karlijn A WoutersSteven E Lipshultz
Mar 7, 2008·European Journal of Heart Failure·Alexander RiadCarsten Tschöpe

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