The extrathyronine actions of iodine as antioxidant, apoptotic, and differentiation factor in various tissues

Abstract

Background: Seaweed is an important dietary component and a rich source of iodine in several chemical forms in Asian communities. Their high consumption of this element (25 times higher than in Western countries) has been associated with the low incidence of benign and cancerous breast and prostate disease in Japanese people.

Summary: We review evidence showing that, in addition to being a component of the thyroid hormone, iodine can be an antioxidant as well as an antiproliferative and differentiation agent that helps to maintain the integrity of several organs with the ability to take up iodine. In animal and human studies, molecular iodine (I2) supplementation exerts a suppressive effect on the development and size of both benign and cancerous neoplasias. Investigations by several groups have demonstrated that these effects can be mediated by a variety of mechanisms and pathways, including direct actions, in which the oxidized iodine dissipates the mitochondrial membrane potential, thereby triggering mitochondrion-mediated apoptosis, and indirect effects through iodolipid formation and the activation of peroxisome proliferator-activated receptors type gamma, which, in turn, trigger apoptotic or differentiation pathways.

Conclusions: We propose that the International Council for the Control of Iodine Deficient Disorders recommend that iodine intake be increased to at least 3 mg/day of I2 in specific pathologies to obtain the potential extrathyroidal benefits described in the present review.

FIG. 1.

Effect of perchlorate (KClO₄) on ¹²⁵I⁻ and ¹²⁵I₂ uptake. Rats were first injected intraperitoneally with KClO₄ (20 mg/kg) or saline (sham injected), and 2 hours later, with 50 μCi of either ¹²⁵I⁻ or ¹²⁵I₂. Animals were sacrificed 1.0 hour after the radioactivity administration. Radioactivity uptake (cpm) was measured in several tissues and normalized to that in the liver (a nonuptake organ); the results are expressed as cpm tissue/cpm liver. Thyroid tissues were obtained from female and male rats. Results are expressed as mean±SD, n=7 rats/group. Data were analyzed with a one-way analysis of variance, and differences between means were evaluated by the Tuckey test. ^a,bDifferent letters indicate significant differences between groups, p<0.05. MG, mammary gland. [Data adapted from Aceves et al. (17).]

FIG. 2.

Iodine antioxidant power. The antioxidant capacity of molecular iodine (I₂) and potassium iodide (KI) was analyzed with the ferric reducing/antioxidant power assay (FRAP). Ascorbic acid was used as positive control. Three reagents were used: sodium acetate and acetic acid buffer (300 mM, pH 3.6); 10 mM 2,4,6-tripyridyl-s-triazine in a 40 mM solution of hydrochloric acid; and a 20 mM solution of ferric chloride hexahydrate prepared with high-performance liquid chromatography–grade water. FRAP reagent was prepared fresh before each analysis by combining these three reagent solutions in the proportions 10:1:1. Ascorbic acid standards were freshly prepared before analysis. The FRAP assay was carried out in a microplate, with sodium acetate buffer (60 μL), ascorbic acid standards (60 μL) or samples (60 μL), and 240 μL of the FRAP reagent; after a 4-minute reaction, the microplate was read at 620 nm.