OXIDATION RESISTANCE OF LDL IS CORRELATED WITH VITAMIN-E STATUS IN BETA-THALASSEMIA-INTERMEDIA

The alteration of the oxidant/antioxidant balance may affect the susce ptibility of low density lipoproteins (LDL) to oxidation in haemolytic disorders such as thalassemia. Thirty patients affected by beta-thala ssemia intermedia were examined, and compared with age-matched healthy controls. The mean amount of vitamin E in the thalassemic LDL was low er than control (p < 0.0001), either when it was calculated on the bas e of LDL protein (61% decrease) or cholesterol (25% decrease). The LDL resistance to Cu2+-induced oxidation, evaluated as the length of the lag phase before the onset of conjugated diene (CD) lipid hydroperoxid e production, was 20% lower than control. Other parameters of LDL susc eptibility to oxidation, such as the rate of lipid peroxidation, R-p, and the total amount of conjugated dienes produced, CDmax, were only s lightly lower than control, which can be explained by a lower content of peroxidable lipids in the thalassemic LDL. Total LDL cholesterol wa s 1.08 x 10(3) and 2.07 x 10(3) mol/mol LDL in thalassemic and in cont rol LDL, respectively. The length of the lag phase in thalassemic LDL shows a strongly positive correlation with its vitamin E content (r = 0.732; p < 0.0001). The r(2)-value of 0.53 provides evidence that more than 50% of the lag phase is determined by vitamin E. Oxidizability o f LDL lipids may explain 22-24% of the lag phase, as calculated by the inverse correlation between the length of the lag phase and CDmax (r = -0.474; p = 0.008; r(2) = 0.22) and R-p (r = -0.499; p = 0.005; r(2) = 0.24). In multiple regression analysis, the lag phase was predictab le to 66% by vitamin E plus CDmax, and to 60% by vitamin E plus R-p. P lasma Vitamin E was 53% lower in thalassemia patients compared to cont rol and positively correlated with vitamin E in the LDL (r = 0.677; p < 0.0001). None of the correlations above were observed in control sub jects. In conclusion, beta-thalassemia is associated with very low lev els of vitamin E in plasma and in LDL, a condition that renders these particles more susceptible to in vitro oxidative modification and may account for atherogenesis-related vascular diseases described in thala ssemia. The present data on a statistically significant correlation be tween abnormally low vitamin E and oxidizability of LDL contribute sub stantially to the hypothesis that vitamin E is a pathophysiologically important determinant of antioxidative protection of LDL. (C) 1998 Els evier Science Ireland Ltd. All rights reserved.