Iodothyronines: oxidative deiodination by hemoglobin and inhibition of lipid peroxidation

Purified rat hemoglobin catalyzes the oxidative degradation of iodothyronines to form iodide and an iodine-containing intermediate that reacts with protein. Hemoglobin also catalyzes peroxidation of linoleic acid. These observations are consistent with the reported intrinsic peroxidase activity of hemoglobin and other heme-proteins. However, incubations containing both linoleic acid and an iodothyronine produced a surprising result: deiodination was stimulated rather than competitively inhibited. In contrast, linoleic-acid peroxidation was inhibited by iodothyronines. Thus, low levels of iodothyronines (2.6 X 10(-7) M) are effective inhibitors of linoleic-acid peroxidation. Thyroxine and reverse T3 were found to be more effective in this antioxidant activity than vitamin E, glutathione, ascorbic acid and DTT. Since linoleic-acid peroxidation proceeds by a propagating free-radical mechanism, we have concluded that iodothyronines can effectively terminate the free-radical chain reaction to become oxidatively deiodinated. Consistent with this antioxidant mechanism, reverse T3 is effective in preserving red cell membranes as measured by the inhibition of erythrocyte hemolysis.