OXIDATIVE STRESS AND ANTIOXIDANT STATUS IN BETA-THALASSEMIA MAJOR - IRON OVERLOAD AND DEPLETION OF LIPID-SOLUBLE ANTIOXIDANTS

Because of continuous blood transfusions, thalassemia patients are sub jected to peroxidative tissue injury by the secondary iron overload. I n accordance, analysis of serum from 42 beta-thalassemia patients, age d 4 to 40 years, showed that the mean concentrations of conjugated die ne lipid hydroperoxides (CD), lipoperoxides evaluated as malondialdehy de/thiobarbituric acid (MDA/TBA) adducts, and protein carbonyls increa sed about twofold with respect to control. Ferritin levels were positi vely 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 hig h tissue iron levels. Marked changes in the antioxidant pattern were a lso observed in all patients. Evidence is presented of a net drop in t he concentration of ascorbate (-44%), vitamin E (-42%), vitamin A (-44 %), beta-carotene (-29%), and lycopene (-67%). On the other hand, an i ncrease 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 l evels of vitamin E were inversely correlated with ferritin (r = -.45; P = .003), suggesting a major consumption of this antioxidant under ir on overload. Nontransferrin bound iron (NTBI) was in the range 4.5 to 54.8 mu g/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 leve ls of transaminases. On the other hand, lipid-soluble antioxidants in thalassemia patients were depleted to the same extent in hepatitis C v irus (HCV)-infected (31 subjects) and in HCV-uninfected (10 subjects), while in the normal range in serum from 30 nonthalassemic patients wi th HCV-related chronic hepatitis. These results point out that the iro n-induced liver damage in thalassemia may play a major role in the dep letion of lipid-soluble antioxidants. The variations of the parameters evaluated in the present study were not correlated with the age of th e patients. Our results suggest that the measurement of peroxidation p roducts, matched with evaluation of antioxidants, may be a simple meas ure of iron toxicity in thalessemia, in addition to the conventional i ndices of iron status. (C) 1996 by The American Society of Hematology.