Relationship between oxidative stress, ferritin and insulin resistance in sickle cell disease

Abstract. -Background: Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by hemolytic anemia. The oxidative phenomena play a significant role in its pathophysiology. Blood transfusions are a therapeutic mainstay in SCD and repeated transfusions can result in iron overload. There is little direct information available to confirm the correlation between the oxidative stress, iron overload and insulin resistance in SCD patients. Objective: To investigate the relationship between iron overload, the disorders of antioxidants and insulin levels in blood of SCD patients and their matched controls. Methods: The antioxidant activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), as well as the malondialdehyde (MDA, the membrane lipid peroxidation products) and carbonyl contents (the oxidative products of proteins) were estimated spectrophotometrically in erythrocytes of patients and control subjects of matched sex and ages. In addition, fasting blood glucose (FBG), ferritin and insulin levels were estimated in the sera of the same subjects. Results: The mean activity values of SOD, CAT and GSH-Px were significantly decreased, whereas the average values of MDA and carbonyl contents were significantly increased in erythrocytes of SCD patients in comparison to the corresponding values of the control subjects. The average levels of FBS, ferritin, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly elevated in the sera of SCD patients as compared to the controls. In addition, both serum ferritin, and oxidative products (expressed as MDA and carbonyl levels) were significantly correlated with blood glucose, insulin level, and HOMA-IR. Conclusion: These findings may explain the role of elevated ferritin and oxidative products (i.e. MDA & carbonyl contents) in the development of insulin resistance and high glucose levels in SCD patients