Nutritional iron restriction diminishes acute complement-dependent lung injury

Abstract

Deferoxamine has been shown to protect rats from lung injury after complement activation by a cobra venom factor (CVF). The purpose of this study was to assess the effect of prior nutritional iron restriction on acute CVF-induced lung injury. Weanling Sprague-Dawley rats given iron-deficient feed developed marked anemia within three weeks. Control rats received the same feed supplemented with 100 mg Fe/kg. Lung injury was assessed by quantitating the amount of 125I-bovine serum albumin ( 125I-BSA) remaining in the lungs 30 minutes after intravenous administration of CVF and 125I-BSA. Injury was expressed as a permeability index (PI), reflecting the amount of radioactivity remaining in the lung parenchyma. The mean PI in the iron restricted group was 29% of that in the control group after correction for PI in saline treated groups, indicating substantial protection in association with iron restriction. The difference was highly significant (p<0.001). Morphometry revealed that the iron restricted rats had significantly fewer neutrophils in the lung after CVF treatment in comparison with controls. Recruitment of neutrophils into the peritoneal cavity following glycogen injection was also impaired in iron deficient rats. Other findings in iron restricted rats included decreased lung non-heme iron content, decreased neutrophil myeloperoxidase activity, increased unsaturated iron binding capacity, and increased plasma antioxidant activity. These findings suggest a net antioxidant effect of nutritional iron restriction in vivo