Multimetal exposure: Challenges in diagnostics, prevention, and treatment.

Extensive use of heavy metals has posed a serious concern for ecosystem and human too. Heavy metals are toxic in nature and their accumulation in human body causes serious disorders such as neurological disease, cardiac disease, gastrointestinal problems, skin disorders, reproductive disease, lungs diseases, and so on. Furthermore, heavy metals not only affect the human health but also have a negative impact on the economy. In the current review, we have elaborated the impact of heavy metal exposure on human health and socioeconomics. We have discussed the molecular mechanism involved in the heavy metal-induced human disorders such as oxidative stress, neuroinflammation, and protein misfolding. Finally, we discussed the preventive measure and treatment strategy that could counter the negative effects of heavy metal intoxications. In conclusion, there is a substantial correlation between heavy metals and the onset and advancement of several health issues. Chelation treatment could be a useful tactic to lessen the toxic metal load and the difficulties that come with it.

Toward a Mechanism-Driven Integrated Framework to Link Human Exposure to Multiple Toxic Metal(loid) Species with Environmental Diseases.

The ongoing anthropogenic pollution of the biosphere with As, Cd, Hg and Pb will inevitably result in an increased influx of their corresponding toxic metal(loid) species into the bloodstream of human populations, including children and pregnant women. To delineate whether the measurable concentrations of these inorganic pollutants in the bloodstream are tolerable or implicated in the onset of environmental diseases urgently requires new insight into their dynamic bioinorganic chemistry in the bloodstream-organ system. Owing to the human exposure to multiple toxic metal(loid) species, the mechanism of chronic toxicity of each of these needs to be integrated into a framework to better define the underlying exposure-disease relationship. Accordingly, this review highlights some recent advances into the bioinorganic chemistry of the Cd2+, Hg2+ and CH3Hg+ in blood plasma, red blood cells and target organs and provides a first glimpse of their emerging mechanisms of chronic toxicity. Although many important knowledge gaps remain, it is essential to design experiments with the intent of refining these mechanisms to eventually establish a framework that may allow us to causally link the cumulative exposure of human populations to multiple toxic metal(loid) species with environmental diseases of unknown etiology that do not appear to have a genetic origin. Thus, researchers from a variety of scientific disciplines need to contribute to this interdisciplinary effort to rationally address this public health threat which may require the implementation of stronger regulatory requirements to improve planetary and human health, which are fundamentally intertwined.

Evaluation of the toxic metals, proximate composition and length-weight relationships of selected fish species from the Gadananathi River, Southern Tamil Nadu.

The present study reveals toxic metals, proximate composition, and growth conditions in seven fish species, aiding their nutritional importance and conditions. The samples of seven different small indigenous fish species, including Xenentodon cancila, Glossogobious giuris, Pseudambassis ranga, Puntius dorsolis, Mystus vittatus, Dawkinsia filamentosa, and Dawkinsia tambraparaniei, were collected in river Gadananathi, Tamilnadu, India. A total 14 fish samples were analyzed for lead, cadmium, and copper using atomic absorption spectrometry. The standard procedures were used to determine the length-weight and proximate composition of the seven fishes. The findings revealed that the seven fish species had variable amounts of metal buildup. Cu levels were highest in D. tambraparniei gills and lowest in M. vittatus gills and livers; nonetheless, substantial amounts of Cu were found in P. dorsalis livers. In the length-weight correlations of the regression parameters of coefficient value r2, the "a" and "b" values revealed a positive allometric growth rate in all fish species except G. giuris and M. vittatus. However, X. cancila had the highest composition in the proximate analysis, while D. tambraparniei and D. filamentosa had the highest protein content mean value at a significant level (P ≤ 0.05). Overall, discrepancies in nutritional content might be related to species, environmental circumstances, fish age and size, and food availability.

Quantification of toxic metals in chicken egg and chicken feed via SOM-artificial neural network.

Poultry products such as meat and eggs are rich sources of proteins, vitamins, and minerals. It is a good indicator of healthy food. Keeping in view, the present study is designed to evaluate the prevalence of toxic heavy metals (lead, nickel, cadmium, and chromium) in chicken eggs and feed. For this purpose, five samples of egg and feed were collected from five different commercial markets in Skardu City. Each sample was prepared using the wet digestion method and analyzed using a flame atomic absorption spectrophotometer. The results showed that lead, nickel, and chromium were present in varying amounts in the feed and egg, with nickel being the most concentrated metal, followed by lead and chromium in egg samples, while the feed samples showed the highest concentration of chromium followed by lead and nickel. However, concentrations of selected heavy metals except cadmium were all above the permissible limit of the World Health Organization. The self-organizing map-artificial neural network is employed for the identification of patterns of heavy metals in chicken feed and egg samples. The lower left neurons of the maps showed higher heavy metal concentrations found in samples taken from Bazar, whereas the rest of the samples showed varied concentrations. A comparison of feed and egg concentrations showed that nickel concentration was lower in feed samples than in egg samples. The lead concentration decreased in eggs except in the Krasmathang feed sample. Chromium concentration presented a negative correlation due to the extremely high concentration found in the Bazar feed sample.

Hormones and the antioxidant transduction pathway and gene expression, mediated by Serratia marcescens DB1, lessen the lethality of heavy metals (As, Ni, and Cr) in Oryza sativa L.

Microorganisms have recently gained recognition as efficient biological tool for reducing heavy metal toxicity in crops. In this experiment, we isolated a potent heavy metal (As, Ni, and Cr) resistant rhizobacterium Serratia marcescens DB1 and detected its plant growth promoting traits such as phosphate solubilization, gibberellin synthesis, organic acid production and amino acid regulation. Based on these findings, DB1 was further investigated for application in a rice var. Hwayeongbyeo subjected to 1 mM As, 4 mM Ni, and 4 mM Cr stress. The rice plants treated with Cr and Ni appeared healthy but were lethal, indicating unfitness for consumption due to toxic metal deposition, whereas the plants treated with > 1 mM As instantaneously died. Our results showed that DB1 inoculation significantly decreased metal accumulation in the rice shoots. Particularly, Cr uptake dropped by 16.55% and 22.12% in (Cr + DB1) and (Cr + As + Ni + DB1), respectively, As dropped by 48.90% and 35.82% in (As + DB1) and (Cr + As + Ni + DB1), respectively, and Ni dropped by 7.95% and 19.56% in (Ni + DB1) and (Cr + As + Ni + DB1), respectively. These findings were further validated by gene expression analysis results, which showed that DB1 inoculation significantly decreased the expression of OsPCS1 (a phytochelatin synthase gene), OsMTP1 (a metal transporting gene), and OsMTP5 (a gene for the expulsion of excess metal). Moreover, DB1 inoculation considerably enhanced the morphological growth of rice through modulation of endogenous phytohormones (abscisic acid, salicylic acid, and jasmonic acid) and uptake of essential elements such as K and P. These findings indicate that DB1 is an effective biofertilizer that can mitigate heavy metal toxicity in rice crops.

Maternal blood concentrations of toxic metal(loid)s and trace elements from preconception to pregnancy and transplacental passage to fetuses.

Intrauterine exposure to heavy metals may adversely affect the developing fetus and health later in life, while certain trace elements may be protective. There is limited data on their dynamic fluctuation in circulating concentration of women from preconception to pregnancy and the degree of transplacental passage to fetus. Such information is critically needed for an optimal design of research studies and intervention strategies. In the present study, we profiled the longitudinal patterns and trajectories of metal(loid)s and trace elements from preconception to late pregnancy and in newborns. We measured whole blood metal(loid)s in women at preconception, 16, 24 and 32 weeks of gestation and in cord blood in 100 mother-newborn pairs. Our data showed that the mean concentrations of mercury (Hg), lead (Pb), rubidium (Rb), manganese (Mn), and iron (Fe) were lower during early-, mid-, and late-pregnancy than at preconception. Copper (Cu), and calcium (Ca) concentrations increased after pregnancy (Cu 798 versus 1353, 1488, and 1464 µg/L). Concentrations at preconception were correlated with those during pregnancy for all examined metal(loid)s. Maternal Hg, Pb, and Se concentrations at late-pregnancy were correlated with those in newborn cord blood in various degrees (correlation coefficients: Hg 0.66, Pb 0.29, Se 0.39). The estimated placental transfer ratio for toxic metal(loid)s ranging from 1.68 (Hg) to 0.18 (Cd). Two trajectory groups were identified for Hg, Pb, Cd, Se concentrations. Hg concentrations may be correlated with maternal education levels. The study is the first to present longitudinal circulating concentration trajectories of toxic metal(loid)s and trace elements from preconception to pregnancy stages. A high degree of transplacental passage was observed in toxic metals Pb and Hg which may pose hazards to the developing fetus.

Risk assessment of combined exposure to lead, cadmium, and total mercury among the elderly in Shanghai, China.

Lead (Pb), cadmium (Cd) and total mercury (THg) are toxic heavy metals (THMs) that are widely present in the environment and can cause substantial health problems. However, previous risk assessment studies have rarely focused on the elderly population and have usually targeted a single heavy metal, which might underestimate the long-term accumulative and synergistic effects of THMs in humans. Based on the food frequency questionnaire and inductively coupled plasma mass spectrometry, this study assessed external and internal exposures to Pb, Cd and THg in 1747 elderly people in Shanghai. Probabilistic risk assessment with the relative potential factor (RPF) model was used to assess the neurotoxicity and nephrotoxicity risks of combined THMs exposures. The mean external exposures of Pb, Cd and THg in Shanghai elderly were 46.8, 27.2 and 4.9 µg/day, respectively. Plant-based foods are the main source of Pb and THg exposure, while Cd is mainly from animal-based foods. The mean concentrations of Pb, Cd and THg were 23.3, 1.1 and 2.3 µg/L in the whole blood, and 6.2, 1.0 and 2.0 µg/L in the morning urine, respectively. Combined exposure to THMs leading to 10.0 % and 7.1 % of Shanghai elderly at risk of neurotoxicity and nephrotoxicity. The results of this study have important implications for understanding the profiles of Pb, Cd and THg exposure in the elderly living in Shanghai and provide data support for risk assessment and control of nephrotoxicity and neurotoxicity from combined THMs exposure in the elderly.

Iron Deficiency and Nephrotoxic Heavy Metals: A Dangerous Interplay?

Heavy metals are common in our environment, and all individuals are exposed to them to some extent. These toxic metals have several harmful effects on the body, including the kidney, which is a very sensitive organ. Indeed, heavy metal exposure has been linked to an increased risk of chronic kidney disease (CKD) and its progression, which may be explained by the well-established nephrotoxic effects of these metals. In this hypothesis and narrative literature review, we will shed light on the potential role that another highly common problem in patients with CKD, iron deficiency, may play in the damaging effects of heavy metal exposure in this patient group. Iron deficiency has previously been linked with an increased uptake of heavy metals in the intestine due to the upregulation of iron receptors that also take up other metals. Furthermore, recent research suggests a role of iron deficiency in the retention of heavy metals in the kidney. Therefore, we hypothesize that iron deficiency plays a crucial role in the damaging effects of heavy metal exposure in patients with CKD and that iron supplementation might be a strategy to combat these detrimental processes.

Evaluating Manganese, Zinc, and Copper Metal Toxicity on SH-SY5Y Cells in Establishing an Idiopathic Parkinson's Disease Model.

Parkinson's disease (PD) is a neurodegenerative condition marked by loss of motor coordination and cognitive impairment. According to global estimates, the worldwide prevalence of PD will likely exceed 12 million cases by 2040. PD is primarily associated with genetic factors, while clinically, cases are attributed to idiopathic factors such as environmental or occupational exposure. The heavy metals linked to PD and other neurodegenerative disorders include copper, manganese, and zinc. Chronic exposure to metals induces elevated oxidative stress and disrupts homeostasis, resulting in neuronal death. These metals are suggested to induce idiopathic PD in the literature. This study measures the effects of lethal concentration at 10% cell death (LC10) and lethal concentration at 50% cell death (LC50) concentrations of copper, manganese, and zinc chlorides on SH-SY5Y cells via markers for dopamine, reactive oxygen species (ROS) generation, DNA damage, and mitochondrial dysfunction after a 24 h exposure. These measurements were compared to a known neurotoxin to induce PD, 100 µM 6-hydroxydopamine (6-ODHA). Between the three metal chlorides, zinc was statistically different in all parameters from all other treatments and induced significant dopaminergic loss, DNA damage, and mitochondrial dysfunction. The LC50 of manganese and copper had the most similar response to 6-ODHA in all parameters, while LC10 of manganese and copper responded most like untreated cells. This study suggests that these metal chlorides respond differently from 6-ODHA and each other, suggesting that idiopathic PD utilizes a different mechanism from the classic PD model.

Zebrafish as a Potential Model for Neurodegenerative Diseases: A Focus on Toxic Metals Implications.

In the last century, industrial activities increased and caused multiple health problems for humans and animals. At this moment, heavy metals are considered the most harmful substances for their effects on organisms and humans. The impact of these toxic metals, which have no biological role, poses a considerable threat and is associated with several health problems. Heavy metals can interfere with metabolic processes and can sometimes act as pseudo-elements. The zebrafish is an animal model progressively used to expose the toxic effects of diverse compounds and to find treatments for different devastating diseases that human beings are currently facing. This review aims to analyse and discuss the value of zebrafish as animal models used in neurological conditions, such as Alzheimer's disease (AD), and Parkinson's disease (PD), particularly in terms of the benefits of animal models and the limitations that exist.

S-Nitrosoglutathione (GSNO)-Mediated Lead Detoxification in Soybean through the Regulation of ROS and Metal-Related Transcripts.

Heavy metal toxicity, including lead (Pb) toxicity, is increasing in soils, and heavy metals are considered to be toxic in small amounts. Pb contamination is mainly caused by industrialization (e.g., smelting and mining), agricultural practices (e.g., sewage sludge and pests), and urban practices (e.g., lead paint). An excessive concentration of Pb can seriously damage and threaten crop growth. Furthermore, Pb adversely affects plant growth and development by affecting the photosystem, cell membrane integrity, and excessive production of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) and superoxide (O2-). Nitric oxide (NO) is produced via enzymatic and non-enzymatic antioxidants to scavenge ROS and lipid peroxidation substrates to protect cells from oxidative damage. Thus, NO improves ion homeostasis and confers resistance to metal stress. In the present study, we investigated the effect of exogenously applied NO and S-nitrosoglutathione in soybean plants Our results demonstrated that exogenously applied NO aids in better growth under lead stress due to its ability in sensing, signaling, and stress tolerance in plants under heavy metal stress along with lead stress. In addition, our results showed that S-nitrosoglutathione (GSNO) has a positive effect on soybean seedling growth under lead-induced toxicity and that NO supplementation helps to reduce chlorophyll maturation and relative water content in leaves and roots following strong bursts under lead stress. GSNO supplementation (200 µM and 100 µM) reduced compaction and approximated the oxidative damage of MDA, proline, and H2O2. Moreover, under plant stress, GSNO application was found to relieve the oxidative damage by reactive oxygen species (ROS) scavenging. Additionally, modulation of NO and phytochelatins (PCS) after prolonged metal reversing GSNO application confirmed detoxification of ROS induced by the toxic metal lead in soybean. In summary, the detoxification of ROS caused by toxic metal concentrations in soybean is confirmed by using NO, PCS, and traditionally sustained concentrations of metal reversing GSNO application.

Recent Progress on Fluorescent Probes in Heavy Metal Determinations for Food Safety: A Review.

One of the main challenges faced in food safety is the accumulation of toxic heavy metals from environmental sources, which can sequentially endanger human health when they are consumed. It is invaluable to establish a practical assay for the determination of heavy metals for food safety. Among the current detection methods, technology based on fluorescent probes, with the advantages of sensitivity, convenience, accuracy, cost, and reliability, has recently shown pluralistic applications in the food industry, which is significant to ensure food safety. Hence, this review systematically presents the recent progress on novel fluorescent probes in determining heavy metals for food safety over the past five years, according to fluorophores and newly emerging sensing cores, which could contribute to broadening the prospects of fluorescent materials and establishing more practical assays for heavy metal determinations.

Exposure Assessment of Essential and Potentially Toxic Metals in Wheat-Based Sweets for Human Consumption: Multivariate Analysis and Risk Evaluation Studies.

In recent years, there has been a growing concern about the negative impact of unforeseen contaminants such as metals in commonly consumed food items, which pose a threat to human well-being. Therefore, it is of utmost importance to evaluate the levels of these contaminants to guarantee the safe consumption of these food items. The goal of the current research is to determine the levels of essential (EMs: Mg, Ca, Mn, Fe, Co, Cu, and Zn) and potentially toxic metals (PTMs: Al, Cr, Ni, As, Cd, and Pb) in various brands of wheat-based sweets. One hundred samples were collected and analysed via flame atomic absorption spectrometry (FAAS) and inductively coupled plasma-optical emission spectrometry (ICP-OES). Also, the current study was to investigate the distribution, correlation, and multivariate analysis of 13 metals (Mg, Ca, Mn, Fe, Co, Cu, Zn, Al, Cr, Ni, As, Cd, and Pb). Hierarchical cluster analysis (HCA) and principal component analysis (PCA) were used to interpret the metals' association. The concentration (mg/kg) ranges of EMs were, in order, Mg (12.70-65.67), Ca (24.02-209.12), Mn (1.32-9.61), Fe (4.55-111.23), Co (0.32-8.94), Cu (2.12-8.61), and Zn (2.60-19.36), while the concentration (mg/kg) ranges of PTMs were, in order, Al (0.32-0.87), Cr (0.17-5.74), Ni (0.36-1.54), Cd (0.16-0.56), and Pb (0.14-0.92), and As was not detected in any sample under investigation. The HCA data revealed that Co, Al, and Ni form clusters with other metals. Sweets are prepared at high temperatures, and the elevated temperatures can increase the likelihood of Ni and Al leaching from stainless steel. Tolerable dietary intake (TDI) values for Ni were higher than the values established by the European Food Safety Authority (EFSA). The CR value found for the Ni and Cr was at the threshold level of cancer risk, if an amount of 25 g were to be used over a lifetime. In a nutshell, this study highlights the monitoring of EM and PTM levels in wheat-based sweets, and from a food safety perspective, the study is important for consumers of wheat-based sweets.

Biosorption of toxic metal ions (Cr+6, Cd2+) and nutrients (PO43-) from aqueous solution by diatom biomass.

This paper evaluates diatom biomass as a biosorbent for removing Cr+6, Cd2+, and PO43- ions from water. The diatom was characterized by X-ray Diffraction (XRD), Fourier Transform Infrared (FTIR), and Scanning Electron Microscopy (SEM-EDS) for its crystallinity, functional groups, and morphology. A batch sorption study was conducted to evaluate the parameters influencing Cr+6, Cd2+, and PO43- ions adsorption, and the mechanisms were explored. The FTIR spectra revealed Si-O, O-H, N-H, and C-O as the main functional groups present on the surface of the adsorbent. The SEM showed a rough and irregular-shaped morphology, while the EDS indicated that the diatom biomass is an aluminosilicate material. The rate-limiting steps for Cr+6 and Cd2+ were pseudo-first order, and pseudo-second order sorption favored PO43- based on their R2 values. Moreover, the dominant adsorption model that best described the equilibrium data was the Freundlich isotherm. The maximum adsorption capacities obtained for Cr+6 was 5.66 (mg/g), and Cd2+ was 5.27 (mg/g) at 313 K while PO43- was 19.13 (mg/g) at 298 K. The thermodynamic data revealed that the reaction was endothermic for Cd2+ and exothermic for Cr+6 and PO43-, respectively. Diatom biomass was observed to be a promising bio-sorbent for removing Cr6+, Cd2+ and PO42- from wastewater.

Monitoring the spatial distribution pattern according to urban land use and health risk assessment on potential toxic metal contamination via street dust in Ankara, Türkiye.

The urbanization processes with growing vehicle numbers cause heavy metal pollution in street dust, and high populations in metropolitan cities are exposed to pollutants. This paper aims to monitor the spatial distribution of heavy metals and evaluate the concentrations via health risk assessment of HMs (Cu, Ni, Cd, Co, Pb, and Zn) that expose the inhabitants to health hazards. According to the results of the current study, sixty street dust samples were applied to the acid digestion technique and quantification by inductively coupled plasma-mass spectrometry (ICP-MS). The spatial distribution of the selected heavy metals in the street dust was investigated using the spatial analysis tool in ArcGIS 10.0 according to population density and land use. In the present study, we used hazard index and cancer risk methods to estimate the public health risk of the pollutants exposed to street dust in Ankara. The concentrations range of the elements in street dust over the study area ranged from 3.34-4.50, 31.69-42.87, 16.09-21.54, 42.85-57.55, 0.00-3.51, and 23.03-30.79, respectively. The overall decreasing order of mean concentration of metals was observed as follows: Pb > Cu > Ni > Co > Cd > Zn. Vehicle traffic and industrial activities seem to be the most critical anthropogenic sources responsible for dust pollution in the study area. The risk assessment of Pb and Ni exposure was the highest, and the hazard index values were 2.42E + 00 and 2.28E + 00 mg/kg/day for children. However, the effect on adults was 2.62E-01 and 2.37E-02 mg/kg/day, followed by inhalation and dermal contact with street dust was almost negligible. The decreasing concentration is modeled spatially along the western development corridor of the city. The risk to public health is high in areas with high densities close to the city center and the main artery.

The role of chemical fractionation in risk assessment of toxic metals: a review.

The identification of highly toxic metals like Cd, Ni, Pb, Cr, Co or Cu in ambient particulate matter (PM) has garnered a lot of interest recently. Exposure to toxic metals, including carcinogenic ones, at levels above recommended limits, can significantly affect human health. Prolonged exposure to even trace amounts of toxic or essential metals can also have negative health impacts. In order to assess significant risks, it is crucial to govern the concentrations of bioavailable/bio-accessible metals that are available in PM. Estimating the total metal concentrations in PM is only an approximation of metal toxicity. This review provides an overview of various procedures for extracting soluble toxic metals from PM and the importance of chemical fractionation in risk assessment. It is observed that the environmental risk indices such as bioavailability index (BI), contamination factor (CF) and risk assessment code (RAC) are specifically influenced by the concentration of these metals in a particular fraction. Additionally, there is compelling evidence that health risks assessed using total metal concentrations may be overestimated, therefore, the metal toxicity assessment is more accurate and more sensitive to the concentration of the bioavailable/bio-accessible fraction than the total metal concentrations. Hence, chemical fractionation of toxic metals can serve as an effective tool for developing environmental protection laws and improving air quality monitoring programs for public health.

Potentially toxic metals contamination, health risk, and source apportionment in the agricultural soils around industrial areas, Firozabad, Uttar Pradesh, India: a multivariate statistical approach.

Potentially toxic metals (PTMs) contamination in the soil poses a serious danger to people's health by direct or indirect exposure, and generally it occurs by consuming food grown in these soils. The present study assessed the pollution levels and risk to human health upon sustained exposure to PTM concentrations in the area's centuries-old glass industry clusters of the city of Firozabad, Uttar Pradesh, India. Soil sampling (0-15 cm) was done in farmers' fields within a 1 km radius of six industrial clusters. Various environmental (geo-accumulation index, contamination factor, pollution load index, enrichment factor, and ecological risk index) and health risk indices (hazard quotient, carcinogenic risk) were computed to assess the extent of damage caused to the environment and the threat to human health. Results show that the mean concentrations of Cu (33 mg kg-1), Zn (82.5 mg kg-1), and Cr (15.3 mg kg-1) were at safe levels, whereas the levels of Pb, Ni, and Cd exceeded their respective threshold limits. A majority of samples (88%) showed considerable ecological risk due to the co-contamination of these six PTMs. Health risk assessment indicated tolerable cancer and non-cancer risk in both adults and children for all PTMs, except Ni, where adults were exposed to potential threat of cancer. Pearson's correlation study revealed a significant positive correlation between all six metal pairs and conducting principal component analysis (PCA) confirmed the common source of metal pollution. The PC score ranked different sites from highest to lowest according to PTM loads that help to establish the location of the source. Hierarchical cluster analysis grouped different sites into the same cluster based on similarity in PTMs load, i.e., low, medium, and high.

Chemistry, Pharmacology, and Toxicology of Monoisoamyl Dimercaptosuccinic Acid: A Chelating Agent for Chronic Metal Poisoning.

Arsenic, a metalloid, is known to cause deleterious effects in various body organs, particularly the liver, urinary bladder, and brain, and these effects are primarily mediated through oxidative stress. Chelation therapy has been considered one of the promising medical treatments for arsenic poisoning. Meso 2,3- dimercaptosuccinic acid (DMSA) has been recognized as one of the most effective chelating drugs to treat arsenic poisoning. However, the drug is compromised with a number of shortcomings, including the inability to treat chronic arsenic poisoning due to its extracellular distribution. Monoisoamyl 2,3-dimercaptosuccinic acid, one of the analogues of meso 2,3-dimeraptosuccinic acid (DMSA), is a lipophilic chelator and has shown promise to be considered as a potential future chelating agent/antidote not only for arsenic but also for a few other heavy metals like lead, mercury, cadmium, and gallium arsenide. The results from numerous studies carried out in the recent past, mainly from our group, strongly support the clinical application of MiADMSA. This review paper summarizes most of the scientific details including the chemistry, pharmacology, and safety profile of MiADMSA. The efficacy of MiADMSA mainly against arsenic toxicity but also a few other heavy metals was also discussed. We also reviewed a few other strategies in order to achieve the optimum effects of MiADMSA, like combination therapy using two chelating agents or coadministration of a natural and synthetic antioxidant (including phytomedicine) along with MiADMSA for treatment of metal/metalloid poisoning. We also briefly discussed the use of nanotechnology (nano form of MiADMSA i.e. nano-MiADMSA) and compared it with bulk MiADMSA. All these strategies have been shown to be beneficial in getting more pronounced therapeutic efficacy of MiADMSA, as an adjuvant or as a complementary agent, by significantly increasing the chelating efficacy of MiADMSA.

Gene expression and oxidative stress markers profile associated with toxic metals in patients with renal cell carcinoma.

BACKGROUND: Toxic metals are associated with cancer progression. Studies have reported the relation between some toxic metals and renal cell carcinoma (RCC). METHODS AND RESULTS: Blood levels of Cd and Pb were determined in 94 RCC patients (RCC group) and 91 matched controls as well as blood level of malondialdehyde (MDA) and catalase (CAT) activity as markers of oxidative stress and antioxidant, respectively. Gene expression of MAP kinase pathway (P38 and JNK), hypoxia-inducible factor 1-alpha (HIF1α), vascular endothelial growth factor (VEGF), cytochrome C oxidase subunit 6 (COX6), metallothionein (MT2A), and heat shock protein (HSP90AA1) were evaluated in the obtained tissue specimens. Blood Cd and Pb levels were significantly higher in RCC group comparing to control group with preferential significant increase of Cd in chromophobe RCC (chRCC) sub-type. MDA level was significantly higher and CAT activity was lower in the RCC compared to controls. The difference was evident only in chRCC. The expressions of genes were significantly increased in the cancer tissues than in non-cancerous tissues in RCC sub-types and there was a significant correlation between Cd levels and expression of genes VEGF, MT2A, P38 and JNK in chRCC group. Immunohistochemical staining of clear cell RCC tissues shows a marked expression of VEGF and HIF-1α.While COX6 staining show marked expression in chRCC. CONCLUSIONS: There is a positive correlation between Cd toxicity and the development of RCC, especially chRCC sub-type. Cd is strongly incriminated in the pathogenesis of chRCC through the effort on some genes and oxidative stress markers.

Metal Profiles in Autism Spectrum Disorders: A Crosstalk between Toxic and Essential Metals.

Since hundreds of years ago, metals have been recognized as impacting our body's physiology. As a result, they have been studied as a potential cure for many ailments as well as a cause of acute or chronic poisoning. However, the link between aberrant metal levels and neuropsychiatric illnesses such as schizophrenia and neurodevelopmental disorders, such as autism spectrum disorders (ASDs), is a relatively new finding, despite some evident ASD-related consequences of shortage or excess of specific metals. In this review, we will summarize past and current results explaining the pathomechanisms of toxic metals at the cellular and molecular levels that are still not fully understood. While toxic metals may interfere with dozens of physiological processes concurrently, we will focus on ASD-relevant activity such as inflammation/immune activation, mitochondrial malfunction, increased oxidative stress, impairment of axonal myelination, and synapse formation and function. In particular, we will highlight the competition with essential metals that may explain why both the presence of certain toxic metals and the absence of certain essential metals have emerged as risk factors for ASD. Although often investigated separately, through the agonistic and antagonistic effects of metals, a common metal imbalance may result in relation to ASD.