Chapter 51 - Oxidative Damage in Iodine Deficiency

Abstract

Severe iodine deficiency may impair thyroid hormone synthesis and cause a compensatory increase in H2O2 concentration in thyrocytes. This may result in more prolonged exposure to oxygen-free radicals, which in turn may extend reactive oxygen species (ROS)-mediated oxidative damage including DNA, induce mutations, and possibly contribute to degenerative changes in tissues. High levels of cell proliferation and higher replication rates during thyroid enlargement may also prevent mutation repair and implement mutations into the genome. High levels of H2O2 may lead to oxidative stress and in turn LP and oxidative DNA modifications, causing higher mutation rates, although thyroid cells very likely have an effective mechanism, including several forms of selenoenzymes, to regulate antioxidative response that counters the potential threat of oxidant stress. When there is selenium deficiency coupled with iodine deficiency, through an increased availability of H2O2 and a decrease in thyroid GPx activity, the stimulated thyroid gland is possibly exposed to greater levels of H2O2, and in turn, to highly reactive peroxides. Oxidative DNA damage caused by ROS or other DNA damaging agents has been implicated in mutagenesis, carcinogenesis, reproductive cell death and aging. Therefore, although the high concentration of intracellular H2O2 allows a higher efficiency of thyroid hormone synthesis, the thyroid gland is a source of oxygen radicals in iodine and selenium deficiency. It is therefore plausible that deficits of antioxidant status, in addition to iodine deficiency, may lead to the exposure of thyroid cells to increased oxidative stress and damage, and may eventually contribute to the occurrence of malignant transformations.