Peroxidation, vitamin E, and sickle-cell anemia.
In summary, we propose the following scheme (Figure 5) to describe the role of peroxidation in the pathophysiology of SCA. Sickle erythrocytes are more susceptible to peroxidation than are normal erythrocytes. This increased susceptibility to peroxidation is, in part, due to decreased blood vitamin E levels and abnormal membrane phospholipid organization induced by sickling. The peroxidative damage of sickle erythrocytes may accelerate or contribute to loss of cell deformability and to chronic hemolysis. Peroxidative damage can produce abnormal cellular properties, such as potassium leak and reduced filterability, and contribute to formation of ISCs. Increased red cell rigidity can initiate episodes of capillary obstruction, leading to vasoocclusive painful crises and to tissue infarction. Liver dysfunction as well as increased production of bilirubin secondary to hemolysis could result in bile sludging and decreased secretion of bile salts into the intestinal lumen. Reduced bile salt secretion leads to partial fat and vitamin E malabsorption. Vitamin E deficiency enhances red cell susceptibility to peroxidation and promotes a vicious cycle in SCA. Although we have not studied factors that might initiate peroxidative damage, sickle hemoglobin and excess body iron should be considered as potential sources. Our studies suggest that vitamin E supplementation to sickle-cell patients could be of clinical benefit.
D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007408:Intestinal Absorption; D010545:Peroxides / Q000097:blood*; D011188:Potassium / Q000097:blood; D014810:Vitamin E / Q000378:metabolism*; D014811:Vitamin E Deficiency / Q000150:complications
D010545:Peroxides; D014810:Vitamin E; D006861:Hydrogen Peroxide; D011188:Potassium