Iron-overload cardiomyopathy: evidence for a free radical--mediated mechanism of injury and dysfunction in a murine model.
Iron-overload cardiomyopathy is a restrictive cardiomyopathy that manifests itself as systolic or diastolic dysfunction secondary to increased deposition of iron in the heart and occurs with common genetic disorders such as primary hemochromatosis and beta-thalassemia major. Although the exact mechanism of iron-induced heart failure remains to be elucidated, the toxicity of iron in biological systems is believed to be attributed to its ability to catalyze the generation of oxygen-free radicals. In the current investigation, the dose-dependent effects of chronic iron-loading on heart tissue concentrations of iron, glutathione peroxidase (GPx) activity, free-radical production, and cardiac dysfunction were investigated in a murine model of iron-overload cardiomyopathy. It was shown that chronic iron-overload results in dose-dependent (a) increases in myocardial iron burden, (b) decreases in the protective antioxidant enzyme GPx activity, (c) increased free-radical production, and (d) increased mortality. These findings show that the mechanism of iron-induced heart dysfunction involves in part free radical-mediated processes.
School of Nursing, Queen's University, 90 Barrie Street, Kingston, Ontario, Canada, K7L 3N6. bartfayw@post.queensu.ca
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D000818:Animals; D001822:Body Burden; D002313:Cardiomyopathy, Restrictive / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000032:analysis; D006439:Hemodynamics; D007501:Iron / Q000032:analysis; D019190:Iron Overload / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism*; D007505:Iron-Dextran Complex; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009206:Myocardium / Q000737:chemistry; D011897:Random Allocation
D005609:Free Radicals; D007505:Iron-Dextran Complex; D007501:Iron; D005979:Glutathione Peroxidase