This Article Full Text Full Text (PDF) All Versions of this Article: 109/15/1877    most recent 01.CIR.0000124229.40424.80v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Oudit, G. Y. Articles by Backx, P. H. Search for Related Content PubMed PubMed Citation Articles by Oudit, G. Y. Articles by Backx, P. H. Related Collections Nutrition Contractile function Other heart failure Congestive Animal models of human disease Apoptosis Oxidant stress

(Circulation. 2004;109:1877-1885.)
© 2004 American Heart Association, Inc.

Basic Science Reports

Taurine Supplementation Reduces Oxidative Stress and Improves Cardiovascular Function in an Iron-Overload Murine Model

Gavin Y. Oudit, MSc, MD; Maria G. Trivieri, MD; Neelam Khaper, PhD; Taneya Husain, BSc; Greg J. Wilson, MD; Peter Liu, MD; Michael J. Sole, MD; Peter H. Backx, DVM, PhD

From the Departments of Physiology and Medicine, Toronto General Hospital, University Health Network, Heart and Stroke/Richard Lewar Centre of Excellence (G.Y.O., M.G.T., N.K., P.L., M.J.S., P.H.B.), and the Department of Pathology, Hospital for Sick Children (T.H., G.J.W.), University of Toronto, Toronto, Ontario, Canada.

Correspondence to Dr Michael Sole, MD, FRCP(C), FACC, FAHA, Professor of Medicine and Physiology, University of Toronto, Division of Cardiology, University Health Network and Mount Sinai Hospital, Room 13-212 EN, 200 Elizabeth St, Toronto, Ontario, Canada, M5G 2C4. E-mail michael.sole{at}uhn.on.ca

Received October 23, 2002; de novo received October 16, 2003; revision received December 15, 2003; accepted January 7, 2004.

Background— Iron overload has an increasing worldwide prevalence and is associated with significant cardiovascular morbidity and mortality. Elevated iron levels in the myocardium lead to impaired systolic and diastolic function and elevated oxidative stress. Taurine accounts for 25% to 50% of the amino acid pool in myocardium, possesses antioxidant properties, and can inhibit L-type Ca²⁺ channels. Thus, we hypothesized that this agent would reduce the cardiovascular effects of iron overload.

Methods and Results— Iron-overloaded mice were generated by intraperitoneal injection of iron either chronically (5 days per week for 13 weeks) or subacutely (5 days per week for 4 weeks). Iron overload causes increased mortality, elevated oxidative stress, systolic and diastolic dysfunction, hypotension, and bradycardia. Taurine supplementation increased myocardial taurine levels by 45% and led to reductions in mortality and improved cardiac function, heart rate, and blood pressure in iron-overloaded mice. Histological examination of the myocardium revealed reduced apoptosis and interstitial fibrosis in iron-overloaded mice supplemented with taurine. Taurine mediated reduced oxidative stress in iron-overloaded mice along with attenuation of myocardial lipid peroxidation and protection of reduced glutathione level.

Conclusions— These results demonstrate that treatment with taurine reduces iron-mediated myocardial oxidative stress, preserves cardiovascular function, and improves survival in iron-overloaded mice. The role of taurine in protecting reduced glutathione levels provides an important mechanism by which oxidative stress–induced myocardial damage can be curtailed. Taurine, as a dietary supplement, represents a potential new therapeutic agent to reduce the cardiovascular burden from iron-overload conditions.

Key Words: hemochromatosis • cardiomyopathy • taurine • stress, oxidative • glutathione

This article has been cited by other articles:

				R. Basu, G. Y. Oudit, X. Wang, L. Zhang, J. R. Ussher, G. D. Lopaschuk, and Z. Kassiri Type 1 diabetic cardiomyopathy in the Akita (Ins2WT/C96Y) mouse model is characterized by lipotoxicity and diastolic dysfunction with preserved systolic function Am J Physiol Heart Circ Physiol, December 1, 2009; 297(6): H2096 - H2108. [Abstract] [Full Text] [PDF]

				W.-W. Kuo, T.-C. Hsu, M.-H. Chain, C.-H. Lai, W.-H. Wang, F.-J. Tsai, C.-H. Tsai, C.-H. Wu, C.-Y. Huang, and B.-S. Tzang Attenuated Cardiac Mitochondrial-dependent Apoptotic Effects by Li-Fu Formula in Hamsters Fed with a Hypercholesterol Diet Evid. Based Complement. Altern. Med., November 25, 2009; (2009) nep182v1. [Abstract] [Full Text] [PDF]

				T. F. Reardon and D. G. Allen Time to fatigue is increased in mouse muscle at 37°C; the role of iron and reactive oxygen species J. Physiol., October 1, 2009; 587(19): 4705 - 4716. [Abstract] [Full Text] [PDF]

				T. F. Reardon and D. G. Allen Iron injections in mice increase skeletal muscle iron content, induce oxidative stress and reduce exercise performance Exp Physiol, June 1, 2009; 94(6): 720 - 730. [Abstract] [Full Text] [PDF]

				N. Anderson and J. Borlak Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis Pharmacol. Rev., September 1, 2008; 60(3): 311 - 357. [Abstract] [Full Text] [PDF]

				S.-D. Lee, W.-W. Kuo, D.-T. Bau, F.-Y. Ko, F.-L. Wu, C.-H. Kuo, F.-J. Tsai, P. S. Wang, M.-C. Lu, and C.-Y. Huang The coexistence of nocturnal sustained hypoxia and obesity additively increases cardiac apoptosis J Appl Physiol, April 1, 2008; 104(4): 1144 - 1153. [Abstract] [Full Text] [PDF]

				A. O. Gramolini, T. Kislinger, R. Alikhani-Koopaei, V. Fong, N. J. Thompson, R. Isserlin, P. Sharma, G. Y. Oudit, M. G. Trivieri, A. Fagan, et al. Comparative Proteomics Profiling of a Phospholamban Mutant Mouse Model of Dilated Cardiomyopathy Reveals Progressive Intracellular Stress Responses Mol. Cell. Proteomics, March 1, 2008; 7(3): 519 - 533. [Abstract] [Full Text] [PDF]

				R. C. Mishra, S. Tripathy, K. M. Desai, D. Quest, Y. Lu, J. Akhtar, and V. Gopalakrishnan Nitric Oxide Synthase Inhibition Promotes Endothelium-Dependent Vasodilatation and the Antihypertensive Effect of L-Serine Hypertension, March 1, 2008; 51(3): 791 - 796. [Abstract] [Full Text] [PDF]

				U. Merle, E. Fein, S. G. Gehrke, W. Stremmel, and H. Kulaksiz The Iron Regulatory Peptide Hepcidin Is Expressed in the Heart and Regulated by Hypoxia and Inflammation Endocrinology, June 1, 2007; 148(6): 2663 - 2668. [Abstract] [Full Text] [PDF]

				I. T. Mak, J. J. Chmielinska, L. Nedelec, A. Torres, and W. B. Weglicki D-Propranolol Attenuates Lysosomal Iron Accumulation and Oxidative Injury in Endothelial Cells J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 522 - 528. [Abstract] [Full Text] [PDF]

				J. H. Kramer, S. B. Murthi, R. M. Wise, I-T. Mak, and W. B. Weglicki Antioxidant and lysosomotropic properties of acute d-propranolol underlies its cardioprotection of postischemic hearts from moderate iron-overloaded rats. Experimental Biology and Medicine, April 1, 2006; 231(4): 473 - 484. [Abstract] [Full Text] [PDF]

				K. Saito, N. Ishizaka, T. Aizawa, M. Sata, N. Iso-o, E. Noiri, I. Mori, M. Ohno, and R. Nagai Iron chelation and a free radical scavenger suppress angiotensin II-induced upregulation of TGF-{beta}1 in the heart Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1836 - H1843. [Abstract] [Full Text] [PDF]