Iron Chelation Reduces DNA Damage in Sickle Cell Anemia.

Sickle cell anemia (SCA) is a blood condition that causes severe pain. One of the therapeutic agents used for the treatment of SCA is hydroxyurea, which reduces the episodes of pain but causes DNA damage to white blood cells. The aim of this study was to evaluate the efficacy of the combination of hydroxyurea and iron chelation therapy in relation to the extent of DNA-associated damage. Blood samples were collected from 120 subjects from five groups. Various hematological parameters of the obtained serum were analyzed. The amount of damage caused to their DNA was detected using the comet assay and fluorescent microscopy techniques. The percentage of DNA damage in the group that was subjected to the combination therapy (target group) was 1.32% ± 1.51%, which was significantly lower (P < .05) than that observed in the group treated with hydroxyurea alone (6.36% ± 2.36%). While the target group showed comparable levels of hemoglobin F and lactate dehydrogenase compared to the group that was treated with hydroxyurea alone, highly significant levels of transferrin receptors and ferritin were observed in the target group. The results of this study revealed that the administration of iron chelation drugs with hydroxyurea may help improve patients' health and prevent the DNA damage caused to white blood cells due to hydroxyurea. Further studies are needed to better understand the underlying mechanisms that are involved in this process.

Markers of endothelial dysfunction and leucocyte activation in Saudi and non-Saudi haplotypes of sickle cell disease.

Sickle cell disease (SCD) is an autosomal recessive inherited hemoglobinopathy, characterized by chronic hemolysis and recurrent vaso-occlusive crisis (VOC). This study investigates changes in leucocyte subsets and the relationship between cell adhesion molecule expression and disease manifestations in patients during steady state and acute VOC. We compared soluble E-selectin and P-selectin levels in 84 SCD patients, in steady state and during VOC to 84 healthy controls. Using immunophenotyping, we also compared lymphocyte subsets in these three groups. Further, we compared E-selectin and P-selectin levels in patients of Saudi ethnicity to non-Saudi patients, in all three groups. Lymphocyte subsets showed high percentages of total T lymphocytes, T helper and suppressor lymphocytes, B lymphocytes as well as NK cells in patients with SCD during steady state, while B lymphocytes and NK cells were significantly higher during acute VOC crisis. High levels of both soluble E-selectin (sE-selectin) and soluble P-selectin (sP-selectin) markers were demonstrated in the serum of patients with SCD during both steady state and acute VOC. Levels of selectins were significantly higher in acute VOC. The immunophenotypic expression of L-selectin, on leucocytes, was high in SCD both during steady state and during acute VOC in comparison to normal control subjects. There was no significant difference in all three study groups between Saudi and non-Saudi patients. These findings suggest that patients with SCD have increased expression of adhesion molecules: E-selectin and P-selectin, which play an important role in the pathogenesis of VOC. Despite the distinct phenotype of Saudi patients with SCD, there was no significant difference in levels of soluble E-selectin and soluble P-selectin between Saudi and non-Saudi patients in all three groups. While sickle cell disease is a well-recognized state of chronic inflammation, the role of specific adhesion molecules is steadily unraveling. Studies are underway to investigate the potential role of selectin antagonists, for prevention and reversal of acute vascular occlusions in SCD patients.