One-step determination of total iron using deferiprone or kojic acid as colorimetric reagents

The role of iron, one of the most common metals in the environment, is fundamental in many biological and geochemical processes, which determine its availability in the two main oxidation states Fe2+ and Fe3+. Its relevance in the environment, industrial applications, and human physiology, as well as in many other fields has constantly encouraged the development of analytical techniques for its accurate determination. Spectrophotometric methods are those most frequently applied for iron determination in real samples, with specific reagents for the two existing oxidation state right now. In the present work, two low-cost, non-toxic, colorimetric reagents are proposed: deferiprone and kojic acid. These compounds present peculiar features, in particular the formation of 1:3 complexes with Fe3+ of extremely high stability and absorptivity in a wide operative pH range. In this study, we show that both reagents can be used to measure the total iron content. Actually, the extremely low redox potential characterizing the FeL3 complexes permits to determine the total concentration of iron independently from the starting oxidation state, and assures the complete oxidation in presence of oxygen of any amount of Fe2+ to Fe3+ complexes. These features constitute a novelty in the analytical determination of total iron not requiring any pretreatment of the sample, contrary to the methods in use, devoted either to Fe3+ or to Fe2+, necessitating awkward and error generating oxidative or reductive processes. The analytical performance of the proposed spectrophotometric method has been evaluated for the full compliance with the Lambert-Beer law, the operative range of iron concentration, the influence of pH, and the interfering effects of other metal ions. Finally, it has been validated in terms of LoD, LoQ, linearity, precision, and trueness, and has been tested on total iron determination in natural water certified material and in two biological reference materials, human urine and serum

Arsenic toxicity: Molecular targets and therapeutic agents

High arsenic (As) levels in food and drinking water, or under some occupational conditions, can precipitate chronic toxicity and in some cases cancer. Millions of people are exposed to unacceptable amounts of As through drinking water and food. Highly exposed individuals may develop acute, subacute, or chronic signs of poisoning, characterized by skin lesions, cardiovascular symptoms, and in some cases, multi-organ failure. Inorganic arsenite(III) and organic arsenicals with the general formula R-As2+ are bound tightly to thiol groups, particularly to vicinal dithiols such as dihydrolipoic acid (DHLA), which together with some seleno-enzymes constitute vulnerable targets for the toxic action of As. In addition, R-As2+-compounds have even higher affinity to selenol groups, e.g., in thioredoxin reductase that also possesses a thiol group vicinal to the selenol. Inhibition of this and other ROS scavenging seleno-enzymes explain the oxidative stress associated with arsenic poisoning. The development of chelating agents, such as the dithiols BAL (dimercaptopropanol), DMPS (dimercapto-propanesulfonate) and DMSA (dimercaptosuccinic acid), took advantage of the fact that As had high affinity towards vicinal dithiols. Primary prevention by reducing exposure of the millions of people exposed to unacceptable As levels should be the prioritized strategy. However, in acute and subacute and even some cases with chronic As poisonings chelation treatment with therapeutic dithiols, in particular DMPS appears promising as regards alleviation of symptoms. In acute cases, initial treatment with BAL combined with DMPS should be considered

A review on coordination properties of thiol-containing chelating agents towards mercury, cadmium, and lead

The present article reviews the clinical use of thiol-based metal chelators in intoxications and overexposure with mercury (Hg), cadmium (Cd), and lead (Pb). Currently, very few commercially available pharmaceuticals can successfully reduce or prevent the toxicity of these metals. The metal chelator meso-2,3-dimercaptosuccinic acid (DMSA) is considerably less toxic than the classical agent British anti-Lewisite (BAL, 2,3-dimercaptopropanol) and is the recommended agent in poisonings with Pb and organic Hg. Its toxicity is also lower than that of DMPS (dimercaptopropane sulfonate), although DMPS is the recommended agent in acute poisonings with Hg salts. It is suggested that intracellular Cd deposits and cerebral deposits of inorganic Hg, to some extent, can be mobilized by a combination of antidotes, but clinical experience with such combinations are lacking. Alpha-lipoic acid (alpha-LA) has been suggested for toxic metal detoxification but is not considered a drug of choice in clinical practice. The molecular mechanisms and chemical equilibria of complex formation of the chelators with the metal ions Hg2+, Cd2+, and Pb2+ are reviewed since insight into these reactions can provide a basis for further development of therapeutics

A speciation study on the perturbing effects of iron chelators on the homeostasis of essential metal ions

A number of reports have appeared in literature calling attention to the depletion of essential metal ions during chelation therapy on beta-thalassaemia patients. We present a speciation study to determine how the iron chelators used in therapy interfere with the homeostatic equilibria of essential metal ions. This work includes a thorough analysis of the pharmacokinetic properties of the chelating agents currently in clinical use, of the amounts of iron, copper and zinc available in plasma for chelation, and of all the implied complex formation constants. The results of the study show that a significant amount of essential metal ions is complexed whenever the chelating agent concentration exceeds the amount necessary to coordinate all disposable iron-a frequently occurring situation during chelation therapy. On the contrary, copper and zinc do not interfere with iron chelation, except for a possible influence of copper on iron speciation during deferiprone treatment

The aging kidney—as influenced by heavy metal exposure and selenium supplementation

The aging process in the kidneys has been well studied. It is known that the glomerular filtration rate (GFR) declines with age in subjects older than 50–60 years. However, there is still insufficient knowledge regarding the response of the aged kidney to environmental toxicants such as mercury, cadmium, and lead. Here, we present a review on the functional decline and proposed mechanisms in the aging kidney as influenced by metal pollutants. Due to the prevalence of these toxicants in the environment, human exposure is nearly unavoidable. Further, it is well known that acute and chronic exposures to toxic metals may be detrimental to kidneys of normal adults, thus it may be hypothesized that exposure of individuals with reduced GFR will result in additional reductions in renal function. Individuals with compromised renal function, either from aging or from a combination of aging and disease, may be particularly susceptible to environmental toxicants. The available data appear to show an association between exposure to mercury, cadmium and/or lead and an increase in incidence and severity of renal disease in elderly individuals. Furthermore, some physiological thiols, as well as adequate selenium status, appear to exert a protective action. Further studies providing improved insight into the mechanisms by which nephrotoxic metals are handled by aging kidneys, as well as possibilities of therapeutic protection, are of utmost importance

A family of kojic acid derivatives aimed to remediation of Pb2+ and Cd2+

The present work analyzes the complex formation ability towards Pb2+ and Cd2+ of a series of kojic acid derivatives that join the chelating properties of the pyrone molecules and those of polyamines, with the aim of evaluating how the different effects of oxygen and nitrogen coordinating groups act on the stability of metal complexes. Experimental research is carried out using potentiometric and spectrophotometric techniques supported by 1H and 13C NMR spectroscopy and DFT calculations. Actually, a different coordination mechanism toward Pb2+ and Cd2+ was proved: in the case of Pb2+, coordination takes place exclusively via the oxygen atoms, while the contribute of the nitrogen atoms appears relevant in the case of Cd2+. Lead complexes of all the studied ligands are characterized by significantly stronger stability than those of cadmium. Finally, on the basis of the measured complex formation stabilities, some of the proposed molecules seems promising effective ligands for lead and cadmium ion decorporation from polluted soils or waste waters

The Role of Magnesium in Pregnancy and in Fetal Programming of Adult Diseases

Magnesium is an essential trace metal and a necessary factor for multiple biochemical functions in humans. Its role in biology is fundamental in over 600 enzymatic reactions implicated in protein synthesis, mitochondrial functions, neuromuscular activity, bone formation, and immune system competence. Magnesium status is relevant in fetal development during gestation and in the newborn growth during the perinatal period. Moreover, magnesium is able to influence fetal programming and disease presentation in childhood or adulthood. The aim of this review is to focus on this metal homeostasis, analyzing its normal values, the causes of hypomagnesemia, the interaction with drugs and other conditions, and the diseases associated with magnesium value alteration during pregnancy, in order to study its role in fetal programming of adult diseases. The data here reported clearly indicated the existence of a connection between magnesium status and human pathology starting from intrauterine life and extending into childhood and adulthood

The value of some Corsican sub-populations for genetic association studies

<p>Abstract</p> <p>Background</p> <p>Genetic isolates with a history of a small founder population, long-lasting isolation and population bottlenecks represent exceptional resources in the identification of disease genes. In these populations the disease allele reveals Linkage Disequilibrium (LD) with markers over significant genetic intervals, therefore facilitating disease locus identification. In a previous study we examined the LD extension on the Xq13 region in three Corsican sub-populations from the inner mountainous region of the island. On the basis of those previous results we have proposed a multistep procedure to carry out studies aimed at the identification of genes involved in complex diseases in Corsica. A prerequisite to carry out the proposed multi-step procedure was the presence of different degrees of LD on the island and a common genetic derivation of the different Corsican sub-populations. In order to evaluate the existence of these conditions in the present paper we extended the analysis to the Corsican coastal populations.</p> <p>Methods</p> <p>Samples were analyzed using seven dinucleotide microsatellite markers on chromosome Xq13-21: DXS983, DXS986, DXS8092, DXS8082, DXS1225, DXS8037 and DXS995 spanning approximately 4.0 cM (13.3 Mb). We have also investigated the distribution of the DXS1225-DXS8082 haplotype which has been recently proposed as a good marker of population genetic history due to its low recombination rate.</p> <p>Results</p> <p>the results obtained indicate a decrease of LD on the island from the central mountainous toward the coastal sub-populations. In addition the analysis of the DXS1225-DXS8082 haplotype revealed: 1) the presence of a particular haplotype with high frequency; 2) the derivation from a common genetic pool of the sub-populations examined in the present study.</p> <p>Conclusion</p> <p>These results indicate the Corsican sub-populations useful for the fine mapping of genes contributing to complex diseases.</p

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes