Postischemic tissue injury by iron-mediated free radical lipid peroxidation.
Cell damage initiated during ischemia matures during reperfusion. Mechanisms involved during reperfusion include the effects of arachidonic acid and its oxidative products prostaglandins and leukotrienes, reperfusion tissue calcium overloading, and damage to membranes by lipid peroxidation. Lipid peroxidation occurs by oxygen radical mechanisms that require a metal with more than one ionic state (transitional metal) for catalysis. We have shown that cellular iron is delocalized from the large molecules where it is normally stored to smaller chemical species during postischemic reperfusion. Postischemic lipid peroxidation is inhibited by the iron chelator deferoxamine. Intervention in the reperfusion injury of membranes by chelation of transitional metals is a new and promising therapeutic possibility for protection of the heart and brain.
D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects; D003676:Deferoxamine / Q000627:therapeutic use; D005609:Free Radicals; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D008054:Lipid Peroxides / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D010101:Oxygen Consumption; D012151:Resuscitation; D014022:Tissue Survival
D005609:Free Radicals; D008054:Lipid Peroxides; D007501:Iron; D003676:Deferoxamine; D002118:Calcium