EFFECTS OF IODOTYROSINES, THYRONINES, IODOTHYROACETIC ACIDS AND THYROMIMETIC ANALOGS ON IN-VITRO COPPER-INDUCED OXIDATION OF LOW-DENSITY LIPOPROTEINS

We studied the effect of different thyroid compounds [(I-2, monoiodo-L -tyrosine (MIT), diiodo-L-tyrosine (DIT), L-thyronine (T-0), 3,5-diiod o-L-thyronine (T-2), 3,5,3'-triiodo-L-thyronine (T-3), 3,3',5'-triiodo -L-thyronine (rT(3)),3,5,3',5'-tetraiodo-L-thyronine (T-4),3,5-diiodo thyroacetic acid (TA(2)), 3,5,3'-triiodo-thyroacetic acid (TA(3)) and 3,5,3',5'-tetraiodothyroacetic acid (TA(4))] or thyromimetics [(3,5-di methyl-3'-isopropyl-L- thyronine (DIMIT) and 3,5-diiodo-3'-isopropyl-t hyroacetic acid (lpTA(2))] on in vitro copper-induced oxidation of low -density lipoproteins (LDL). Human native LDL (0.05 g protein/L) oxida tion was induced by 2.5 mu mol/L of CuCl2. Conjugated dienes were meas ured spectrophotometrically for up to 10 hr. The length of the lag pha se (T-lag), maximum velocity of the reaction (V-max) and the maximum a mount of generated dienes were obtained from kinetic data. T-3 increas ed T-lag and decreased V-max with a dependence upon concentration (0 t o 3 mu mol/L). There was no difference between the D-max obtained with Cu2+ alone or in the presence of the various compounds (1 mu mol/L). I-2, MIT and DIT did not modify any parameter of the oxidation kinetic . T-0 and T-2 had the same antioxidant efficiency as T-3, whereas T-4 only decreased V-max. rT(3) increased T-lag less than did T-3, whereas DIMIT was the thyronine that had the most important effect. TA(2) and TA(3) were the most efficient antioxidant compounds. TA(4) decreased T-lag less than TA(3) did, whereas lpTA(2) had an effect weaker than t hat of the physiological acetic derivatives. The data suggest that thy roid hormones and derivatives have LDL-antioxidant properties, their i mportance being related to their 4'-hydroxy diphenyl ether structure a nd depending upon the nature and the position of substituents in this structure. (C) 1998 Elsevier Science Inc.