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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Effects of iodotyrosines, thyronines, iodothyroacetic acids and thyromimetic analogues on in vitro copper-induced oxidation of low-density lipoproteins.

We studied the effect of different thyroid compounds [(I2, monoiodo-L-tyrosine (MIT), diiodo-L-tyrosine (DIT), L-thyronine (T0), 3,5-diiodo-L-thyronine (T2), 3,5,3'-triiodo-L-thyronine (T3), 3,3',5'-triiodo-L-thyronine (rT3), 3,5,3',5'-tetraiodo-L-thyronine (T4), 3,5-diiodothyroacetic acid (TA2), 3,5,3'-triiodothyroacetic acid ( TA3) and 3,5,3',5'-tetraiodothyroacetic acid ( TA4)] or thyromimetics [(3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) and 3,5-diiodo-3'-isopropyl-thyroacetic acid (IpTA2)] on in vitro copper-induced oxidation of low-density lipoproteins (LDL). Human native LDL (0.05 g protein/L) oxidation was induced by 2.5 micromol/L of CuCl2. Conjugated dienes were measured spectrophotometrically for up to 10 hr. The length of the lag phase (Tlag), maximum velocity of the reaction (Vmax) and the maximum amount of generated dienes were obtained from kinetic data. T3 increased Tlag and decreased Vmax with a dependence upon concentration (0 to 3 micromol/L). There was no difference between the Dmax obtained with Cu2+ alone or in the presence of the various compounds (1 micromol/L). I2, MIT and DIT did not modify any parameter of the oxidation kinetic. T0 and T2 had the same antioxidant efficiency as T3, whereas T4 only decreased Vmax. rT3 increased Tlag less than did T3, whereas DIMIT was the thyronine that had the most important effect. TA2 and TA, were the most efficient antioxidant compounds. TA4 decreased Tlag less than TA3 did, whereas IpTA2 had an effect weaker than that of the physiological acetic derivatives. The data suggest that thyroid hormones and derivatives have LDL-antioxidant properties, their importance being related to their 4'-hydroxy diphenyl ether structure and depending upon the nature and the position of substituents in this structure.[1]


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