Transferrin delays oxygen radical induced cardiac-contractile failure.
The role of iron-loaded transferrin in xanthine-xanthine oxidase (X-XO) induced cardiac injury in isolated perfused rat hearts was examined. X (2 mM) - XO (10 U/L) perfusion resulted in contractile failure, a rise in resting tension, an increase in lipid peroxidation, and myocardial cell damage. The addition of transferrin (2.4 microM) into the X-XO medium had a protective effect, as indicated by an increase in time to contractile failure, a lesser rise in resting tension, a decrease in MDA values, and lesser damage compared with the X-XO perfused controls. Ultrastructural studies revealed localization of transferrin along the capillary basement membrane. In contrast, addition of transferrin and Desferal (desferrioxamine mesylate, 3 mM, an iron chelator) into X-XO medium caused a rapid contractile failure as well as a rise in resting tension, and in these hearts transferrin was localized inside the myocytes. These findings suggest that a vascular supply of iron protein chelators may have a beneficial effect against myocardial cell injury caused by a vascular source of oxygen radicals.
Tiede
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Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Man., Canada.
Sareen
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Singal
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D000818:Animals; D001485:Basement Membrane / Q000648:ultrastructure; D003676:Deferoxamine / Q000494:pharmacology; D005609:Free Radicals; D006333:Heart Failure / Q000503:physiopathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000648:ultrastructure; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014168:Transferrin / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000633:toxicity
D005609:Free Radicals; D014168:Transferrin; D008315:Malondialdehyde; D014969:Xanthine Oxidase; D003676:Deferoxamine