EFFECT OF MILD IRON OVERLOAD ON LIVER AND KIDNEY LIPID-PEROXIDATION

1. Hepatotoxicity is the most common finding in patients with iron ove rload since the liver is the major recipient of iron excess, even thou gh the kidney could be a target of iron toxicity. The effect of iron o verload was studied in the early stages after iron-dextran injection i n rats, as a model for secondary hemocromatosis. 2. Total hepatic and kidney iron content was markedly elevated over control values 20 h aft er the iron administration. Plasma GOT, GPT and LDH activities were no t affected, suggesting that liver cell permeability was not affected b y necrosis. 3. Spontaneous liver chemiluminescence was measured as an indicator of oxidative stress and lipid peroxidation. Light emission w as increased four-fold 6 h after iron supplementation. 4. Increases in the generation of thiobarbituric acid reactive substances (TBARS) in liver and kidney homogenates were detected after iron administration. 5. The activities of catalase, SOD and glutathione peroxidase were det ermined. Enzymatic activities declined in liver homogenates by 25, 36 and 32%, respectively, 20 h after iron injection. These activities wer e not affected in kidney as compared to control values, except for SOD activity that was decreased by 26%. 6. The content of alpha-tocophero l was decreased by 31% in whole kidney homogenates and by 40% in plasm a. 7. Our data indicate that lipid peroxidation occurs after mild iron overload both in liver and kidney. Enzymatic antioxidants are consume d significantly in liver and a-tocopherol content decreases in kidney, suggesting an organ-specific antioxidant effect.