beta-carotene and Anemia--Sickle-Cell

Reactive oxygen species, along with reactive nitrogen species, may play an important role in the pathogenesis and progress of many diseases, including cancer, diabetes and sickle cell disease. It has been postulated that hydroxyurea, one of the main treatments in sickle cell disease, achieves its activity partly also through its antioxidant properties. A series of hydroxyurea derivatives of L- and D-amino acid amides and cycloalkyl-N-aryl-hydroxamic acids was synthesized and investigated for their radical scavenging activity, chelating properties and antioxidant activity. All the compounds showed exceptional antiradical activities. For example, free radical scavenging activities of investigated hydroxyureas were higher than the activity of standard antioxidant, butylated hydroxyanisole (BHA). Moreover, most of the investigated hydroxamic acids were stronger Fe²⁺ ion chelators than quercetin. In addition, the investigated compounds, especially hydroxamic acids, were proven to be excellent antioxidants. They were as effective as BHA in inhibiting β-carotene-linoleic acid coupled oxidation. It is reasonable to assume that the antioxidant activity of the investigated compounds could contribute to their previously proven biological properties as cytostatic and antiviral agents.

Topics: Anemia, Sickle Cell; beta Carotene; Biphenyl Compounds; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Free Radical Scavengers; Humans; Hydroxamic Acids; Hydroxyurea; Iron; Iron Chelating Agents; Linoleic Acid; Magnetic Resonance Spectroscopy; Neoplasms; Oxidation-Reduction; Picrates; Reactive Oxygen Species; Spectrophotometry, Infrared

In previous studies, we found that homozygous sickle cell (HbSS) patients, compared with their healthy (HbAA) counterparts, had reduced levels of the omega-3 fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, in red cells, platelets, and mononuclear cells. These differences were not due to lower intake of the two fatty acids. We have investigated whether reduced antioxidant status in the patients could help explain the observed phenomenon. Blood specimens previously obtained for fatty acid study from Nigerian (26 HbSS and 30 HbAA) and British (30 HbSS, 9 sickle cell-hemoglobin C/HbSC, and 15 HbAA) subjects were analyzed for antioxidant status. The Nigerian HbSS patients compared with the controls had lower plasma retinol, alpha-tocopherol, and beta-carotene concentrations (p < 0.005) and reduced activity of red cell Cu/Zn-superoxide dismutase (Cu/Zn-SOD) (p < 0.05). Similarly, the British HbSS group had reduced concentrations of plasma alpha-tocopherol (p < 0.005), and activities of red cell Cu/Zn-superoxide dismutase (p < 0.05) and Se-glutathione peroxidase (Se-GPx) (p < 0.005) than the controls. In addition, the British patients in comparison with those who had HbSC, a mild form of the disease, had lower alpha-tocopherol than that of the HbAA controls (p < 0.005). In the British sickle cell patients, there was a positive correlation between red cell ethanolamine phosphoglyceride (EPG) DHA and Cu/Zn-SOD activity (r = 0.700, p < 0.05), choline phosphoglyceride (CPG) DHA and Se-GPx activity (r = 0.605, p < 0.05), and CPG EPA and Se-GPx activity (r = 0.558, p > 0.05). Similarly, the percent DHA in red cell EPG was positively related with the activity of Se-GPx in the patients with HbSC (r = 0.674, p < 0.05). These findings suggest that the lower levels of membrane EPA and DHA in blood cells of the HbSS patients could be due to peroxidation resulting from a compromised antioxidant competence.

Topics: Adolescent; Adult; Aged; alpha-Tocopherol; Analysis of Variance; Anemia, Sickle Cell; Antioxidants; beta Carotene; Child; Docosahexaenoic Acids; Eicosapentaenoic Acid; Glutathione Peroxidase; Humans; Middle Aged; Nigeria; Oxidative Stress; Phosphatidylethanolamines; Superoxide Dismutase; United Kingdom; Vitamin A; Young Adult

In 24 adults with hemoglobin SS followed at the Duke University Comprehensive Sickle Cell Center, we have studied the following nutritional parameters: reduced ascorbic acid; dehydroascorbic acid; alpha and beta carotenes; cryptoxanthin; and alpha and gamma tocopherols in whole blood, washed red blood cells, plasma, or serum. In the same population we also examined reduced glutathione (GSH) and oxidized glutathione (GSSG). Fifteen of these 24 patients also were interviewed for usual dietary intakes using a 28-day dietary history. Data obtained from patients with hemoglobin SS, sickle cell anemia (SCA) were compared to those found for seven healthy normal black adults of similar age. Plasma alpha tocopherol levels were significantly lower in SCA individuals than those of the controls (P less than 0.004). Alpha and gamma tocopherol levels in sickle RBCs were significantly higher than those from RBC suspensions of control subjects (P less than 0.007, and P less than 0.001, respectively). All serum values for carotenoids examined, specifically, beta carotene, alpha carotene, and cryptoxanthin were also markedly depressed when compared to those of healthy controls (P less than 0.001, P less than 0.002, and P less than 0.001, respectively). No other statistically significant differences were found between the two groups for any of the remaining variables, including dietary estimates. Dietary analyses suggest that dietary intakes of SCA individuals exceeded the recommended daily allowances (RDA) of all macro- and micronutrients measured, and intakes of most nutrients exceeded those of black controls interviewed. These results suggest that in individuals with SCA, several micronutrients vital to maintaining reducing capacity are present in diminished quantities in plasma/serum. These anomalies exist in SCA patients even though their intake of these micronutrients are similar to those of healthy black men and women.

Topics: Adult; Anemia, Sickle Cell; Ascorbic Acid; beta Carotene; Carotenoids; Cryptoxanthins; Diet; Female; Hemoglobins; Humans; Male; Middle Aged; Nutritional Status; Regression Analysis; Vitamin E; Xanthophylls