Oxidative stress and antioxidant status in beta-thalassemia major: iron overload and depletion of lipid-soluble antioxidants

Abstract

Because of continuous blood transfusions, thalassemia patients are subjected to peroxidative tissue injury by the secondary iron overload. In accordance, analysis of serum from 42 beta-thalassemia patients, aged 4 to 40 years, showed that the mean concentrations of conjugated diene lipid hydroperoxides (CD), lipoperoxides evaluated as malondialdehyde/ thiobarbituric acid (MDA/TBA) adducts, and protein carbonyls increased about twofold with respect to control. Ferritin levels were positively correlated with the amount of MDA (r = .41; P = .007) and showed a positive trend with CD (r = .31; P = .07) and protein carbonyls (r = .35; P = .054), as further evidence of the deleterious effects of high tissue iron levels. Marked changes in the antioxidant pattern were also observed in all patients. Evidence is presented of a net drop in the concentration of ascorbate (-44%), vitamin E (-42%), vitamin A(-44%), beta-carotene (-29%), and lycopene (-67%). On the other hand, an increase of uric acid and bilirubin was observed, whereas serum albumin and glutathione were in the normal range in all patients. As a result, the total serum antioxidant potential, measured as trolox equivalent antioxidant capacity appeared significantly decreased by 14%. Serum levels of vitamin E were inversely correlated with ferritin (r = -.45; P = .003), suggesting a major consumption of this antioxidant under iron overload. Nontransferrin bound iron (NTBI) was in the range 4.5 to 54.8 micrograms/dL (mean, 21.8 +/- 13.9). Although NTBI had a positive trend with ferritin (r = .37, P = .03), no clear correlation was found with either MDA or vitamin E. A mild to severe hepatic damage, as assessed by serum transaminases, was shown in 24 of 42 patients. Serum levels of vitamin E (r = -.49, P = .015), vitamin A (r = -.48, P = .016) and lycopene (r = -.47, P = .020), were inversely correlated with the levels of transminases. On the other hand, lipid-soluble antioxidants in thalassemia patients were depleted to the same extent in hepatitis C virus (HCV)-infected (31 subjects) and in HCV-uninfected (10 subjects), while in the normal range in serum from 30 nonthalassemic patients with HCV-related chronic hepatitis. These results point out that the iron-induced liver damage in thalassemia may play a major role in the depletion of lipid-soluble antioxidants. The variations of the parameters evaluated in the present study were not correlated with the age of the patients. Our results suggest that the measurement of peroxidation products, matched with evaluation of antioxidants, may be a simple measure of iron toxicity in thalessemia, in addition to the conventional indices of iron status.

Iron status and oxidative stress in β‐thalassemia patients in Jakarta

“…Lipid soluble antioxidants, vitamin E (α-tocopherol), vitamin A (retinol), β-carotene and the watersoluble vitamin C are lower in patients than in controls. Similar tendency has been reported by others [15,24,31]. In parallel, reactive thiol groups in the plasma, in plasma proteins, and in RBC membranes [1] decrease.…”

“…Increased intestinal iron absorption in all thalassemic patients due to their anemic situation and regular blood transfusions to thalassemia major patients lead to iron overload especially in the latter group. Improvement is achieved by iron chelation therapy to transfusion-dependent patients even though they still exhibit symptoms of severe oxidative stress [15].…”

“…This is consistent with almost two-fold total serum iron levels in our patients, low total iron binding capacity (TIBC), and extremely low unsaturated iron binding capacity (UIBC) as compared to controls. On the other hand, bilirubin is a potent antioxidant and contributes to the total antioxidant capacity in blood circulation of thalassemic patients [15].…”

“…Hemoglobin (Hb)-screening was performed in the laboratory of the Thalassemia Ward with a VARI-ANT Hemoglobin Testing System. Lipid-soluble antioxidants were measured in the SEAMEO-TROPMED Nutrition laboratory according to the methods described by [15]. Protein was measured according to [16] and thiols were determined according to Ellman [7].…”

“…Inter alia, the disturbed iron metabolism generates oxygen-derived free radicals in thalassemias. This condition, together with impaired natural factors and mechanisms involved in detoxification of ROS and free radicals, results in extensive oxidative stress [15].…”