A role for iron in oxidant-mediated ischemic injury to intestinal microvasculature.
Recent reports in the literature suggest that iron plays an important role in free radical-mediated injury in biological systems. To assess the role of iron-catalyzed oxidant production in ischemia-reperfusion injury, we examined the influence of deferoxamine (an iron chelator) and apotransferrin (iron transporting protein) on the increased intestinal vascular permeability produced by 1 h of ischemia and reperfusion. Both agents were administered intravascularly as a constant infusion, beginning 5 min before reperfusion. Capillary osmotic reflection coefficients were derived from the relationship between lymph-to-plasma protein concentration ratio and lymph flow in the feline small bowel. Vascular permeability in control intestinal preparations was 0.08 +/- 0.005, however it increased significantly to 0.40 +/- 0.03 in preparations subjected to 1 h of ischemia and 30 min of reperfusion. Vascular permeability in the deferoxamine-(0.15 +/- 0.009) and apotransferrin- (0.17 +/- 0.002) treated animals were significantly lower (P less than 0.01) than in the untreated group. Treatment with iron-loaded deferoxamine or transferrin did not offer any protection against ischemic injury. These findings support the hypothesis that iron plays an important role in the formation of hydroxyl radicals after reperfusion of the ischemic bowel.
D000818:Animals; D001059:Apoproteins / Q000494:pharmacology; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects; D002415:Cats; D003676:Deferoxamine / Q000494:pharmacology; D005609:Free Radicals / Q000494:pharmacology; D006878:Hydroxides / Q000378:metabolism*; D017665:Hydroxyl Radical; D007422:Intestines / Q000098:blood supply*; D007501:Iron / Q000494:pharmacology / Q000502:physiology*; D007511:Ischemia / Q000473:pathology*; D014168:Transferrin / Q000494:pharmacology
D001059:Apoproteins; D005609:Free Radicals; D006878:Hydroxides; D014168:Transferrin; C028284:apotransferrin; D017665:Hydroxyl Radical; D007501:Iron; D003676:Deferoxamine