Current Chemical Biology - Volume 5, Issue 3, 2011

Most investigations of iodine metabolism in humans and animals have focused on its role in thyroid function. Public health policies have been established to supply deficient populations with the necessary amount of this element in order to eradicate the iodine deficiency diseases, primarily cretinism. However, considerable evidence indicates that iodine could also be implicated in the physiology of other organs. In humans, the total amount of iodine in the body is 30-50 mg, and less than 30% of it is present in the thyroid gland and its hormones. About 60% of total iodine is non-hormonal and is concentrated in extrathyroidal tissues, where its biological role is still unknown. Moreover, it has been demonstrated that iodine distribution in the organism depends on the chemical form of iodine ingested, and that molecular iodine (I2) is not totally reduced to iodide (I-) in the blood before it is absorbed systemically from the gastrointestinal tract. Indeed, in iodine deficiency conditions, I- appears to be more efficient than I2 in restoring the thyroid gland from a goitrous to a normal state, whereas I2 supplementation diminishes the symptoms of mammary fibrosis in women, causes a 50-70% reduction in the occurrence of mammary cancer induced chemically in rats and exhibit antiproliferative and apoptotic effects in several human tumoral cell lines. Nevertheless, these findings have been viewed with caution, because exposure to moderate or high iodine is thought to be a potential risk to thyroid physiology. Careful examination shows that pathological responses occurred at low or moderate iodine intake in patients with underlying or evident thyroid pathology (e.g. Hashimoto's thyroiditis, history of treated Graves' diseases, etc.); in normal subjects, however, these pathologies occurred only with excessively high doses of iodine or iodide (>20 mg/day). No damaging effects were reported in either the human or animal studies that used therapeutic I2 concentrations (3 to 15 mg/day). This issue will provide an overview of so-called extrathyroidal iodine, its role, and its potential clinical applications.

The significance of inorganic and organic forms of iodine in the evolution of plants and animals is reviewed. Iodine is one of the most electron-rich atoms in the diet of marine and terrestrial organisms, and it enters cells via iodide transporters. Iodide, which acts as a primitive electron donor through peroxidase enzymes, has an ancestral antioxidant function in all iodide-concentrating cells from primitive marine algae to more recent terrestrial vertebrates. Similarly, thyroxine and iodothyronines show antioxidant activities through deiodinase enzymes. About 500-600 million years ago, in parallel with the evolution of the primitive brain in marine animals, thyroid cells originated from the primitive gut in vertebrates, migrated, and specialized in the uptake and storage of iodo-compounds in a novel follicular “thyroidal” structure, an adaptation that enabled the transition from the iodine-rich ocean to the iodine-deficient terrestrial environment.

Although thyroid gland function is mainly under the control of pituitary TSH, other factors may also play a role in this process. Iodine is not used only by the thyroid to synthesize thyroid hormones but also directly influences a number of parameters such as thyroid proliferation and function. Thyroid autoregulation has been related to intraglandular content of an unknown putative iodocompound. The thyroid is capable of producing different iodolipids such as 6-iododeltalactone (ILδ) and 2-iodohexadecanal (2-IHDA). Data from different laboratories have shown that these iodolipids can inhibit several thyroid parameters suggesting that these compounds may be the intermediates in the thyroid autoregulation process.

Iodine is a scarce element in soil that is essential for human beings. It constitutes the basis of thyroid hormones, which are important for mammalian metabolism and development and are indispensable for fetal brain development. Iodine deficiency causes multiple disorders and is still the major cause of endemic cretinism. Comparison of different national cancer statistics led to the supposition that there might be an inverse correlation between iodine intake and cancer prevalence. Asian countries which traditionally have an extremely high iodine intake in daily diet, attributable to seaweed consumption, attract attention by having a lower average cancer incidence rate. Today, based on extensive animal and cell experiments, it has been shown that iodine in form of molecular iodine undoubtedly exerts antitumor effects by inducing apoptosis. Although first analyses were performed with breast cancer cells exclusively, the antitumor effects of molecular iodine were extended by us to a wider range of other tumors, confirming that the antitumor effect is not limited solely to breast cancer.

A robust body of information supports the notion that moderately high concentrations of iodine may reduce pathologies in several tissues that concentrate iodine. This paper reviews evidence showing iodine to be an antioxidant and apoptotic agent that may contribute to the differentiation of normal mammary and prostate glands. In animal and human studies, molecular iodine (I2) supplements suppress the development and size of both benign and malignant neoplasias in these glands and significantly reduce cellular lipoperoxidation. Iodine, in addition to its incorporation into thyroid hormones, is bound to antiproliferative iodolipids called iodolactones, which, in conjunction with peroxisome proliferatoractivated receptors, may play a role in controlling proliferative pathologies in mammary and prostate glands. These studies are in line with data demonstrating that the high consumption of iodine by certain Asian populations such as in Japan (25 times more than in the Occident) correlates with a low incidence of benign and cancerous breast and prostate diseases. Based on our data we proposed that an I2 supplement should be considered as an adjuvant in the treatment of pathologies in breast and prostate.

Parasitic nematodes are a major cause of human health problems with an estimated 1 billion people infected worldwide by these organisms. Identifying biochemical targets that differ between the parasite and host species is essential for finding effective new anti-parasitic molecules. The free-living nematode Caenorhabditis elegans is a powerful model system for experiments in genetics and developmental biology needed to achieve this goal; however, in-depth understanding of metabolic processes in this organism is limited as it still contains unexplored biochemical pathways. Eukaryotes, including nematodes and humans, share many similar metabolic pathways, which makes specific targeting of nematode parasites challenging. Recent studies suggest that C. elegans and other nematodes may use a plant-like pathway as the major biosynthetic route to phosphatidylcholine. In this pathway, a pair of phosphoethanolamine methyltransferases (PMT) catalyze the sequential methylation of phosphoethanolamine to phosphocholine, which can be incorporated into phosphatidylcholine. RNAi experiments demonstrate that both PMT are required for normal growth and development of C. elegans. Because the PMT are highly conserved across nematode parasites of humans, livestock, and plants, as well as in protozoan parasites, understanding how these enzymes function and the identification of inhibitors will aid in the development of new anti-parasite compounds of potential medical, veterinary, and agricultural value.

We examined the effect of bile on the phospholipids (PL) and the membrane fatty acid (FA) composition in Salmonella enterica serovar Typhimurium (S.Typhimurium) wild type (WT) and seqA mutant strains. Phosphatidylglycerol (PtdGro), phosphatidylethanolamine (PtdEtn) and Cardiolipin (Ptd2Gro) are the major PL present in all the strains. The ox bile stress highly affected the PL contents of the seqA mutant with an unusual decrease in PtdEtn and a great increase in Ptd2Gro and PtdGro proportion compared with the untreated seqA and the isogenic WT strains. FA composition of the total lipid (TL) and the different fractions containing PL were altered. Moreover, seqA and ox bile stress caused an increase in unsaturated FA/saturated FA ratio (UFA/SFA) and there was an increase in the content of C16:1w7 and C18:1w9. This increase in UFA content was compensated by a decrease in the corresponding C17- and C19- cyclic FA (CFA). So these CFA were converted to UFA, which resulted in a high UFA/SFA ratio. This paper provides further evidence consistent with the view that the SeqA protein might regulate biosynthesis of membrane FA and PL of S. Typhimurium and it is required for membrane protection from bile salts during infection process.

Free radicals and oxidants play a dual role as both toxic and beneficial compounds, which in low/moderate concentrations are involved in normal physiological functions but excess production of free radicals or decrease in antioxidant level leads to oxidant stress. Free radicals are produced either from normal cell metabolisms in situ or from different external sources (pollution, cigarette smoke, radiation, medication etc). When an overload of free radicals cannot gradually be destroyed, their accumulation in the body is a harmful process that can mediate damage to cellular structures, including lipids, proteins, RNA and DNA leading to a number of diseases. ROS (reactive oxygen species) and RNS (reactive nitrogen species) in excess can damage biological processes, and this situation has been observed in various acute and chronic diseases such as cancer, autoimmune disorders, aging, cataract, cardiovascular and neurodegenerative diseases. This review deals in depth with the role of free radical generation, the mechanisms of formation and catabolism, and the role in various diseases and the function of different phytoconstituents as a defensive factor in the treatment of diseases caused by free radicals, as in the new era they are conferring less side effects and are compatible to body physiology.

Background and Aim: Moringa, an exceptionally nutritious food plant distributed in the tropical and subtropical regions of the world, is increasingly being used for nutritional supplementation along with a variety of medicinal uses. Being rich in nutrients, various parts of the plant such as the bark, root, fruit (pod), flower, leaves, seed and gum are widely used by traditional healers, nutritionists, and doctors in a variety of illnesses. The immature green pods, called ‘drumsticks’ are probably the most valued and widely used part of the tree for water purification (e.g. desalination of ocean salt water). The leaves being good source of beta-carotene, vitamin C, protein, iron and potassium are used in soups and sauces. Despite an impressive medicinal use and the fact that different parts are being employed for the treatment of various ailments in the indigenous system of medicine, little is known scientifically about the scavenging potential of this plant. Therefore, the present study was undertaken to analyze and compare concentration-dependent hydroxyl radical scavenging ability of Moringa oleifera fruit and leaf extracts (alcoholic and aqueous). Methods and Results: The activity of extracts at different concentrations (10-250μg/mL) was determined both in the presence and/or absence of ascorbic acid and ethylenediamine tetra acetic acid using deoxyribose degradation assay. It was observed that moringa extract scavenges hydroxyl radical at lower concentrations and subsequent increase in concentration suppresses scavenging activity. Conclusion: Based on our observations, it may be inferred that moringa extract especially from the fruit (pod) and leaf part has strong antioxidant property as assessed by its property of scavenging hydroxyl radical formation.