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(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

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