Cytochrome C, a potent oxygen free radical scavenger against the calcium paradox injury in the myocardium.
The calcium paradox was induced by perfusion of hearts with a calcium-free medium for 10 mins followed by calcium-containing medium for 20 mins (group A). During calcium depletion, myocytes were preserved but vascular endothelial cells underwent prominent morphological changes and their plasma membranes were disrupted and transformed to myelin-like whorls. Calcium repletion induced severe myocyte necrosis, massive release of creatine phosphokinase (CPK) and calcium accumulation. The effect of ferricytochrome C on the calcium paradox injury was investigated in groups of hearts; ferricytochrome C (75 microM) was given either during calcium repletion only (group B), during calcium depletion only (group C), or both during calcium depletion and repletion (group D). There was no protection by cytochrome C in group B with no reduction in release of CPK, calcium accumulation or cell damage. However, cytochrome C was very protective when given during calcium depletion (groups C and D). CPK was significantly reduced in groups C and D compared to group A (P less than 0.03) and less calcium accumulation was observed in groups C and D (6.0 +/- 0.8, 12.5 +/- 1.25 mumol) compared to group A (P less than 0.03). Moreover, a significant number of cells was preserved in group C (84%) and group D (80%), compared to group A (2%). This was associated with prevention of vascular damage caused by calcium depletion. The data provide strong evidence that cytochrome C is a potent protective agent against the calcium paradox injury that may be caused by oxygen-derived radicals.
Ashraf
M
M
Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Ohio 45267-0529.
Kossenjans
W
W
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D003574:Cytochrome c Group / Q000494:pharmacology*; D004727:Endothelium / Q000187:drug effects / Q000648:ultrastructure; D005609:Free Radicals; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D003574:Cytochrome c Group; D005609:Free Radicals; D003402:Creatine Kinase; D010100:Oxygen; D002118:Calcium