Hereditary Transthyretin Amyloidosis (hATTR) with Polyneuropathy Clusters Are Located in Ancient Mining Districts: A Possible Geochemical Origin of the Disease.

Hereditary transthyretin amyloidosis (hATTR) with polyneuropathy (formerly known as Familial Amyloid Polyneuropathy (FAP)) is an endemic amyloidosis involving the harmful aggregation of proteins, most commonly transthyretin (TTR) but sometimes also apolipoprotein A-1 or gelsolin. hATTR appears to be transmitted as an autosomal dominant trait. Over 100 point mutations have been identified, with the Val30Met substitution being the most common. Yet, the mechanism of pathogenesis and the overall origin of hATTR remain unclear. Here, we argue that hATTR could be related to harmful metal exposure. hATTR incidence is unevenly distributed globally, and the three largest defined clusters exist in Japan, Portugal, and Sweden. All three disease regions are also ancient mining districts with associated metal contamination of the local environment. There are two main mechanisms for how harmful metals, after uptake into tissues and body fluids, could induce hATTR. First, the metals could directly influence the expression, function, and/or aggregation of the proteins involved in hATTR pathology. Such metal-protein interactions might constitute molecular targets for anti-hATTR drug design. Second, metal exposure could induce hATTR -associated genetic mutations, which may have happened several generations ago. These two mechanisms can occur in parallel. In conclusion, the possibility that hATTR could be related to metal exposure in geochemically defined regions deserves further attention.

Metal Toxicity: Effects on Energy Metabolism in Fish.

Metals are dispersed in natural environments, particularly in the aquatic environment, and accumulate, causing adverse effects on aquatic life. Moreover, chronic polymetallic water pollution is a common problem, and the biological effects of exposure to complex mixtures of metals are the most difficult to interpret. In this review, metal toxicity is examined with a focus on its impact on energy metabolism. Mechanisms regulating adenosine triphosphate (ATP) production and reactive oxygen species (ROS) emission are considered in their dual roles in the development of cytotoxicity and cytoprotection, and mitochondria may become target organelles of metal toxicity when the transmembrane potential is reduced below its phosphorylation level. One of the main consequences of metal toxicity is additional energy costs, and the metabolic load can lead to the disruption of oxidative metabolism and enhanced anaerobiosis.

Assessment of carcinogenic and non-carcinogenic risk of exposure to potentially toxic elements in tea infusions: Determination by ICP-OES and multivariate statistical data analysis.

BACKGROUND: The perennial evergreen tea (Camellia sinensis) plant is one of the most popular nonalcoholic drinks in the world. Fertilizers and industrial, agricultural, and municipal activities are the usual drivers of soil contamination, contaminating tea plants with potentially toxic elements (PTEs). These elements might potentially accumulate to larger amounts in the leaves of plants after being taken up from the soil. Thus, frequent monitoring of these elements is critically important. METHODS: The present study intended to determine PTEs (Al, Cr, Mn, Fe, Co, Ni, Cu, Zn, Cd, and Pb) in both tea leaves and infusions using ICP-OES. Various multivariate data analysis methods such as principal component analysis (PCA) and hierarchical cluster analysis (HCA) were employed to elucidate the potential sources of PTEs contamination, whether from anthropogenic activities or natural origins. Additionally, Pearson's correlation coefficient (PCC) was calculated to assess the relationships between the variables under study. RESULTS: The mean contents (mg/L) of all studied elements in tea infusions decreased in order Mn (150.59 ±â€¯1.66) > Fe (11.39 ±â€¯0.99) > Zn (6.62 ±â€¯0.89) > Cu (5.86 ±â€¯0.62) > Co (3.25 ±â€¯0.64) > Ni (1.69 ±â€¯0.23) > Pb (1.08 ±â€¯0.16) > Cr (0.57 ±â€¯0.09) > Cd (0.46 ±â€¯0.09) > Al (0.05 ±â€¯0.008), indicating that Mn exhibits the highest abundance. The mean concentration trend in tea leaf samples mirrored that of infusions, albeit with higher concentrations of PTEs in the former. The tolerable dietary intake (TDI) value for Ni and provisional tolerable monthly intake (PTMI) value for Cd surpassed the standards set by the WHO and EFSA. Calculated hazard index (HI < 1) and cumulative cancer risk (CCR) values suggest negligible exposure risk. CONCLUSION: Elevated levels of PTEs in commonly consumed tea products concern the public and regulatory agencies.

Renal Sinus Pathologies Depicted by CT Imaging: A Pictorial Review.

Diverse conditions comprise the spectrum of renal sinus pathologies, which have diagnostic and therapeutic implications for patients. Using CT imaging as a lens, this exhaustive review examines the representation of these pathologies. The article begins with a concise synopsis of renal anatomy and the specialized CT methodologies utilized to achieve excellent visualization. Transformational cell carcinoma, leiomyosarcoma, renal cell carcinoma, multilocular nephroma, and lymphoma are among the tumoral origins of the renal sinus pathologies that are investigated. Further, vascular pathologies including fistulas, hematomas, and aneurysms are included in the discourse, along with parapelvic and peripelvic cysts, and lipomatosis. In addition to urolithiasis and encrusted uretero-pyelitis, the review examines the consequences of metal toxicity and non-neoplastic conditions. With a focus on critical CT imaging findings that aid in the provision of an accurate diagnosis, every pathology is meticulously examined. With the intention of improving clinical decision-making and patient care, this article intends to function as a valuable resource for radiologists, clinicians, and researchers who are engaged in the interpretation and comprehension of renal sinus pathologies.

Cadmium toxicity to and accumulation in a soil collembolan (Folsomia candida): major factors and prediction using a back-propagation neural network model.

Accurate prediction of cadmium (Cd) ecotoxicity to and accumulation in soil biota is important in soil health. However, very limited information on Cd ecotoxicity on naturally contaminated soils. Herein, we investigated soil Cd ecotoxicity using Folsomia candida, a standard single-species test animal, in 28 naturally Cd-contaminated soils, and the back-propagation neural network (BPNN) model was used to predict Cd ecotoxicity to and accumulation in F. candida. Soil total Cd and pH were the primary soil properties affecting Cd toxicity. However, soil pH was the main factor when the total Cd concentration was < 3 mg kg-1. Interestingly, correlation analysis and the K-spiked test confirmed nutrient potassium (K) was essential for Cd accumulation, highlighting the significance of studying K in Cd accumulation. The BPNN model showed greater prediction accuracy of collembolan survival rate (R2 = 0.797), reproduction inhibitory rate (R2 = 0.827), body Cd concentration (R2 = 0.961), and Cd bioaccumulation factor (R2 = 0.964) than multiple linear regression models. Then the developed BPNN model was used to predict Cd ecological risks in 57 soils in southern China. Compared to multiple linear regression models, the BPNN models can better identify high-risk regions. This study highlights the potential of BPNN as a novel and rapid tool for the evaluation and monitoring of Cd ecotoxicity in naturally contaminated soils.

Metabolic alterations and mitochondrial dysfunction in human airway BEAS-2B cells exposed to vanadium pentoxide.

Vanadium pentoxide (V+5) is a hazardous material that has drawn considerable attention due to its wide use in industrial sectors and increased release into environment from human activities. It poses potential adverse effects on animals and human health, with pronounced impact on lung physiology and functions. In this study, we investigated the metabolic response of human bronchial epithelial BEAS-2B cells to low-level V+5 exposure (0.01, 0.1, and 1 ppm) using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Exposure to V+5 caused extensive changes to cellular metabolism in BEAS-2B cells, including TCA cycle, glycolysis, fatty acids, amino acids, amino sugars, nucleotide sugar, sialic acid, vitamin D3, and drug metabolism, without causing cell death. Altered mitochondrial structure and function were observed with as low as 0.01 ppm (0.2 µM) V+5 exposure. In addition, decreased level of E-cadherin, the prototypical epithelial marker of epithelial-mesenchymal transition (EMT), was observed following V+5 treatment, supporting potential toxicity of V+5 at low levels. Taken together, the present study shows that V+5 has adverse effects on mitochondria and the metabolome which may result in EMT activation in the absence of cell death. Furthermore, results suggest that high-resolution metabolomics could serve as a powerful tool to investigate metal toxicity at levels which do not cause cell death.

Evaluation of Chronic Effects of Potassium Chloride and Nickel on Survival, Growth, and Reproduction of a Unionid Mussel (Lampsilis siliquoidea).

The ASTM International standard test method for freshwater mussels (E2455-13) recommends 4-week toxicity testing with juveniles to evaluate chronic effects on survival and growth. However, concerns remain that the method may not adequately address the sensitivity of mussels to longer term exposures (>4 weeks), particularly in relation to potential reproductive impairments. No standard method directly evaluates toxicant effects on mussel reproduction. The objectives of the present study were to (1) evaluate toxicity endpoints related to reproduction in fatmucket (Lampsilis siliquoidea) using two common reference toxicants, potassium chloride (KCl) and nickel (Ni); (2) evaluate the survival and growth of juvenile fatmucket in standard 4-week and longer term (12-week) KCl and Ni tests following a method refined from the standard method; and (3) compare the sensitivity of the reproductive endpoints with the endpoints obtained from the juvenile mussel tests. Reproductive toxicity tests were conducted by first exposing female fatmucket brooding mature larvae (glochidia) to five test concentrations of KCl and Ni for 6 weeks. Subsamples of the glochidia were then removed from the adults to determine three reproductive endpoints: (1) the viability of brooded glochidia; (2) the viability of free glochidia in a 24-h exposure to the same toxicant concentrations as their mother; and (3) the success of glochidia parasitism on host fish. Mean viability of brooded glochidia was significantly reduced in the high KCl concentration (26 mg K/L) relative to the control, with a 20% effect concentration (EC20) of 14 mg K/L, but there were no significant differences between the control and any Ni treatment (EC20 > 95 µg Ni/L). The EC20s for viability of free glochidia after the additional 24-h exposure and parasitism success were similar to the EC20s of brooded glochidia. The EC20s based on the most sensitive biomass endpoint in the 4-week juvenile tests were 15 mg K/L and 91 µg Ni/L, similar to or greater than the EC20s from the reproductive KCl and Ni tests, respectively. When exposure duration in the juvenile tests was extended from 4 to 12 weeks, the EC20s decreased by more than 50% in the KCl test but by only 8% in the Ni test. Overall, these results indicate that a standard 4-week test with juvenile mussels can prove effective for estimating effects in chronic exposures with different life stages although a longer term 12-week exposure with juvenile mussels may reveal higher sensitivity of mussels to some toxicants, such as KCl. Environ Toxicol Chem 2024;43:1097-1111. © 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Natural resistance-associated macrophage proteins are involved in tolerance to heavy metal Cd2+ toxicity and resistance to bacterial wilt of peanut (Arachis hypogaea L.).

Peanut (Arachis hypogaea L.) is one of the most important oil and industrial crops. However, heavy-metal pollution and frequent soil diseases, poses a significant threat to the production of green and healthy peanuts. Herein, we investigated the effects of heavy metal Cd2+ toxicity to the peanuts, and screened out two peanut cultivars H108 and YZ 9102 with higher Cd2+-tolerance. RNA-seq revealed that Natural resistance-associated macrophage proteins (NRAMP)-like genes were involved in the Cd2+ stress tolerance in H108. Genome-wide identification revealed that 28, 13 and 9 Nramp-like genes existing in the A. hypogaea, A. duranensis and A. ipaensis, respectively. The 50 peanut NRAMP genes share conserved architectural characters, and they were classified into two groups. Expressions of AhNramps, particularly AhNramp4, AhNramp12, AhNramp19, and AhNramp25 could be greatly induced by not only cadmium toxicity, but also copper and zinc stresses. The expression profiles of AhNramp14, AhNramp16 and AhNramp25 showed significant differences in the H108 (resistance) and H107 (susceptible) under the infection of bacterial wilt. In addition, we found that the expression profiles of AhNramp14, AhNramp16, and AhNramp25 were greatly up- or down-regulated by the application of exogenous salicylic acid, methyl jasmonate, and abscisic acid. The AhNramp25, of which expression was affected by both heavy metal toxicity and bacterial wilt infection, were selected as strong candidate genes for peanut stress breeding. Our findings will provide an additional information required for further analysis of AhNramps involved in tolerance to heavy metal toxicity and resistance to bacterial wilt of peanut.

Non-essential heavy metal effects in cardiovascular diseases: an overview of systematic reviews.

Introduction: Cardiovascular diseases (CVDs) are the most important cause of premature death and disability worldwide. Environmental degradation and cardiovascular diseases are two keys to health challenges, characterized by a constant evolution in an industrialized world that exploits natural resources regardless of the consequences for health. The etiological risk factors of CVDs are widely known and include dyslipidemia, obesity, diabetes, and chronic cigarette consumption. However, one component that is often underestimated is exposure to heavy metals. The biological perspective explains that different metals play different roles. They are therefore classified into essential heavy metals, which are present in organisms where they perform important vital functions, especially in various physiological processes, or non-essential heavy metals, with a no biological role but, nonetheless, remain in the environment in which they are absorbed. Although both types of metal ions are many times chemically similar and can bind to the same biological ligands, the attention given today to nonessential metals in several eukaryotic species is starting to raise strong concerns due to an exponential increase in their concentrations. The aim of this systematic review was to assess possible correlations between exposure to nonessential heavy metals and increased incidence of cardiovascular disease, reporting the results of studies published in the last 5 years through March 2023. Methods: The studies includes reviews retrieved from PubMed, Medline, Embase, and Web of Science databases, in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and following the PICO (Population Intervention Comparison Outcome Population) framework. Results: Eight reviews, including a total of 153 studies, were identified. Seven of these review enlighted the association between CVDs and non-essential heavy metals chronic exposure. Discussion: It is evident that exposure to heavy metals represent a risk factor for CVDs onset. However, further studies are needed to better understand the effects caused by these metals.

Reduced expression of bZIP19 and bZIP23 increases zinc and cadmium accumulation in Arabidopsis halleri.

Zinc is an essential micronutrient for all living organisms. When challenged by zinc-limiting conditions, Arabidopsis thaliana plants use a strategy centered on two transcription factors, bZIP19 and bZIP23, to enhance the expression of several zinc transporters to improve their zinc uptake capacity. In the zinc and cadmium hyperaccumulator plant Arabidopsis halleri, highly efficient root-to-shoot zinc translocation results in constitutive local zinc deficiency in roots and in constitutive high expression of zinc deficiency-responsive ZIP genes, supposedly boosting zinc uptake and accumulation. Here, to disrupt this process and to analyze the functions of AhbZIP19, AhbZIP23 and their target genes in hyperaccumulation, the genes encoding both transcriptional factors were knocked down using artificial microRNAs (amiRNA). Although AhbZIP19, AhbZIP23, and their ZIP target genes were downregulated, amiRNA lines surprisingly accumulated more zinc and cadmium compared to control lines in both roots and shoot driving to shoot toxicity symptoms. These observations suggested the existence of a substitute metal uptake machinery in A. halleri to maintain hyperaccumulation. We propose that the iron uptake transporter AhIRT1 participates in this alternative pathway in A. halleri.

Melatonin as an Ameliorative Agent Against Cadmium- and Lead-Induced Toxicity in Fish: an Overview.

Diverse anthropogenic activities and lack of knowledge on its consequences have promoted serious heavy metal contaminations in different aquatic systems throughout the globe. The non-biodegradable nature of most of these toxic heavy metals has increased the concern on their possible bioaccumulation in aquatic organisms as well as in other vertebrates. Among these aquatic species, fish are most sensitive to such contaminated water that not only decreases their chance of survivability in the nature but also increases the probability of biomagnifications of these heavy metals in higher order food chain. After entering the fish body, heavy metals induce detrimental changes in different vital organs by impairing multiple physiological and biochemical pathways that are essential for the species. Such alterations may include tissue damage, induction of oxidative stress, immune-suppression, endocrine disorders, uncontrolled cell proliferation, DNA damage, and even apoptosis. Although uncountable reports have explored the toxic effects of different heavy metals in diverse fish species, but surprisingly, only a few attempts have been made to ameliorate such toxic effects. Since, oxidative stress seems to be the underlying common factor in such heavy metal-induced toxicity, therefore, a potent and endogenous antioxidant with no side effect may be an appropriate therapeutic solution. Apart from summarizing the toxic effects of two important toxicants, i.e., cadmium and lead in fish, the novelty of the present treatise lies in its arguments in favor of using melatonin, an endogenous free radical scavenger and indirect antioxidant, in ameliorating the toxic effects of heavy metals in any fish species.

Effects of Acute and Subchronic Waterborne Thallium Exposure on Ionoregulatory Enzyme Activity and Oxidative Stress in Rainbow Trout (Oncorhynchus mykiss).

The mechanisms of acute (96-hour) and subchronic (28-day) toxicity of the waterborne trace metal thallium (Tl) to rainbow trout (Oncorhynchus mykiss) were investigated. Specifically, effects on branchial and renal ionoregulatory enzymes (sodium/potassium adenosine triphosphatase [ATPase; NKA] and proton ATPase) and hepatic oxidative stress endpoints (protein carbonylation, glutathione content, and activities of catalase and glutathione peroxidase) were examined. Fish (19-55 g) were acutely exposed to 0 (control), 0.9 (regulatory limit), 2004 (half the acute median lethal concentration), or 4200 (acute median lethal concentration) µg Tl L-1 or subchronically exposed to 0, 0.9, or 141 (an elevated environmental concentration) µg Tl L-1 . The only effect following acute exposure was a stimulation of renal H+ -ATPase activity at the highest Tl exposure concentration. Similarly, the only significant effect of subchronic Tl exposure was an inhibition of branchial NKA activity at 141 µg Tl L-1 , an effect that may reflect the interaction of Tl with potassium ion handling. Despite significant literature evidence for effects of Tl on oxidative stress, there were no effects of Tl on any such endpoint in rainbow trout, regardless of exposure duration or exposure concentration. Elevated basal levels of antioxidant defenses may explain this finding. These data suggest that ionoregulatory perturbance is a more likely mechanism of Tl toxicity than oxidative stress in rainbow trout but is an endpoint of relevance only at elevated environmental Tl concentrations. Environ Toxicol Chem 2024;43:87-96. © 2023 SETAC.

Plastic response of macrophages to metal ions and nanoparticles in time mimicking metal implant body environment.

The paradigm of using metal biomaterials could be viewed from two sides - treatment of wide spectrum of degenerative diseases, and debris release from materials. After implant insertion, metal nanoparticles (NPs) and ions are released not only upon the first contact with cells/tissues, but in continual manner, which is immediately recognized by immune cells. In this work, the effects of metal nanoparticles (TiO2, Ni) and ions (Ni2+, Co2+, Cr3+, Mo6+) on primary human M0 macrophages from the blood samples of osteoarthritic patients undergoing total arthroplasty were studied in order to monitor immunomodulatory effects on the cells in a real-time format. The highest NiNPs concentration of 10 µg/ml had no effect on any of macrophage parameters, while the Ni2+ ions cytotoxicity limit for the cells is 0.5 mM. The cytotoxic effects of higher Ni2+ concentration revealed mitochondrial network fragmentation leading to mitochondrial dysfunction, accompanied by increased lysosomal activity and changes in pro-apoptotic markers. The suppression of M2 cell formation ability was connected to presence of Ni2+ ions (0.5 mM) and TiO2NPs (10 µg/ml). The immunomodulatory effect of Mo6+ ions, controversially, inhibit the formation of the cells with M1 phenotype and potentiate the thread-like shape M2s with increased chaotic cell movement. To summarize, metal toxicity depends on the debris form. Both, metal ions and nanoparticles affect macrophage size, morphological and functional parameters, but the effect of ions is more complex and likely more harmful, which has potential impact on healing and determines post-implantation reactions.

Butyrate Protects and Synergizes with Nicotine against Iron- and Manganese-induced Toxicities in Cell Culture.

Toxic exposures to heavy metals, such as iron (Fe) and manganese (Mn), can result in long-range neurological diseases and are therefore of significant environmental and medical concerns. We have previously reported that damage to neuroblastoma-derived dopaminergic cells (SH-SY5Y) by both Fe and Mn could be prevented by pre-treatment with nicotine. Moreover, butyrate, a short chain fatty acid (SCFA) provided protection against salsolinol, a selective dopaminergic toxin, in the same cell line. Here, we broadened the investigation to determine whether butyrate might also protect against Fe and/or Mn, and whether, if combined with nicotine, an additive or synergistic effect might be observed. Both butyrate and nicotine concentration-dependently blocked Fe and Mn toxicities. Ineffective concentrations of nicotine and butyrate, when combined, provided full protection against both Fe and Mn. Moreover, the effects of nicotine but not butyrate could be blocked by mecamylamine, a non-selective nicotinic antagonist. On the other hand, the effects of butyrate, but not nicotine, could be blocked by beta-hydroxy butyrate, a fatty acid-3 receptor antagonist. These results not only provide further support for neuroprotective effects of both nicotine and butyrate but also indicate distinct mechanisms of action for each one. Furthermore, potential utility of butyrate and nicotine combination against heavy metal toxicities is suggested.

Ecotoxicology of Polymetallic Nodule Seabed Mining: The Effects of Cobalt and Nickel on Phytoplankton Growth and Pigment Concentration.

In order to improve the understanding of the environmental impacts of polymetallic nodule mining, ecotoxicological studies were conducted on the growth of model phytoplankton species Skeletonema costatum and Prorocentrum donghaiense using cobalt and nickel. This study evaluated various physiological and ecological indicators, such as cell proliferation, chlorophyll a, pigments, total protein, and antioxidant enzyme markers. The results show that the introduction of low amounts of cobalt or nickel increased the growth rate of phytoplankton. The phytoplankton benefited from low concentrations of cobalt and nickel stress. The increased protein levels and decreased activity of antioxidant enzymes considerably impacted physiological responses during the promotion of cell abundance. High concentrations of cobalt or nickel resulted in decreased light-absorbing pigments, increased photoprotective pigments, an inactive chlorophyll content, decreased total proteins, and maximal antioxidant enzyme activity in phytoplankton. Throughout the experiment, both the phytoplankton protein and enzyme activity declined with prolonged stress, and the cells underwent age-induced damage. Thus, seabed mining's repercussions on phytoplankton could result in both short-term growth promotion and long-term damage. These consequences depend on the impurity concentrations infiltrating the water, their duration, and the organism's physiological responses.

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.

Butyrate protects and synergizes with nicotine against iron- and manganese-induced toxicities in cell culture: Implications for neurodegenerative diseases.

Toxic exposures to heavy metals, such as iron (Fe) and manganese (Mn), can result in long-range neurological diseases and are therefore of significant environmental and medical concerns. We have previously reported that damage to neuroblastoma-derived dopaminergic cells (SH-SY5Y) by both Fe and Mn could be prevented by pre-treatment with nicotine. Moreover, butyrate, a short chain fatty acid (SCFA) provided protection against salsolinol, a selective dopaminergic toxin, in the same cell line. Here, we broadened the investigation to determine whether butyrate might also protect against Fe and/or Mn, and whether, if combined with nicotine, an additive or synergistic effect might be observed. Both butyrate and nicotine concentration-dependently blocked Fe and Mn toxicities. The ineffective concentrations of nicotine and butyrate, when combined, provided full protection against both Fe and Mn. Moreover, the effects of nicotine but not butyrate could be blocked by mecamylamine, a non-selective nicotinic antagonist. On the other hand, the effects of butyrate, but not nicotine, could be blocked by beta-hydroxy butyrate, a fatty acid-3 receptor antagonist. These results not only provide further support for neuroprotective effects of both nicotine and butyrate but indicate distinct mechanisms of action for each one. Furthermore, potential utility of the combination of butyrate and nicotine against heavy metal toxicities is suggested.

Heavy metals contamination in shrimp and crab from southwest regions in Bangladesh: Possible health risk assessment.

Shrimp and Crab, important sources of protein, are currently being adversely affected by the rising industrialization, which has led to higher levels of heavy metals. The goal of this study was to evaluate the health risks of contamination associated with nine heavy metals (Cd, Pb, Cu, Cr, Zn, Ni, As, Al, and Fe) in two species of shrimp (Macrobrachium rosenbergii and Metapenaeus monoceros) and one species of crab (Scylla serrata) that were collected from the Khulna, Satkhira, and Bagerhat areas of Bangladesh. Inductively coupled plasma-optical emission spectrometry (ICP-OES) was used for the study. The results showed that all metal concentrations in shrimp and crab samples were below the recommended level, indicating that ingestion of these foods would not pose any substantial health risks to individuals. To evaluate the non-carcinogenic health risks, the target hazard quotient (THQ) and hazard index (HI) were determined, and the target cancer risk (TR) was utilized to evaluate the carcinogenic health risks. From the health point of view, this study showed that crustaceans obtained from the study sites were non - toxic (THQ and HI < 1), and long-term, continuous intake is unlikely to pose any significant health hazards (TR = 10-7-10-5) from either carcinogenic or non-carcinogenic effects.

Foliar application of silicon, selenium, and zinc nanoparticles can modulate lead and cadmium toxicity in sage (Salvia officinalis L.) plants by optimizing growth and biochemical status.

Different techniques have been used to alleviate metal toxicity in medicinal plants; accordingly, nanoparticles (NPs) have a noticeable interest in modulating oxidative stresses. Therefore, this work aimed to compare the impacts of silicon (Si), selenium (Se), and zinc (Zn) NPs on the growth, physiological status, and essential oil (EO) of sage (Salvia officinalis  L.) treated with foliar application of Si, Se, and Zn NPs upon lead (Pb) and cadmium (Cd) stresses. The results showed that Se, Si, and Zn NPs decreased Pb accumulation by 35, 43, and 40%, and Cd concentration by 29, 39, and 36% in sage leaves. Shoot plant weight showed a noticeable reduction upon Cd (41%) and Pb (35%) stress; however, NPs, particularly Si and Zn improved plant weight under metal toxicity. Metal toxicity diminished relative water content (RWC) and chlorophyll, whereas NPs significantly enhanced these variables. The noticeable raises in malondialdehyde (MDA) and electrolyte leakage (EL) were observed in plants exposed to metal toxicity; however, they were alleviated with foliar application of NPs. The EO content and EO yield of sage plants decreased by the heavy metals but increased by the NPs. Accordingly, Se, Si, and Zn NPS elevated EO yield by 36, 37, and 43%, respectively, compared with non-NPs. The primary EO constituents were 1,8-cineole (9.42-13.41%), α-thujone (27.40-38.73%), ß-thujone (10.11-12.94%), and camphor (11.31-16.45%). This study suggests that NPs, particularly Si and Zn, boosted plant growth by modulating Pb and Cd toxicity, which could be advantageous for cultivating this plant in areas with heavy metal-polluted soils.

Regulatory mechanisms of sulfur metabolism affecting tolerance and accumulation of toxic trace metals and metalloids in plants.

Soil contamination with trace metals and metalloids can cause toxicity to plants and threaten food safety and human health. Plants have evolved sophisticated mechanisms to cope with excess trace metals and metalloids in soils, including chelation and vacuolar sequestration. Sulfur-containing compounds, such as glutathione and phytochelatins, play a crucial role in their detoxification, and sulfur uptake and assimilation are regulated in response to the stress of toxic trace metals and metalloids. This review focuses on the multi-level connections between sulfur homeostasis in plants and responses to such stresses, especially those imposed by arsenic and cadmium. We consider recent progress in understanding the regulation of biosynthesis of glutathione and phytochelatins and of the sensing mechanism of sulfur homeostasis for tolerance of trace metals and metalloids in plants. We also discuss the roles of glutathione and phytochelatins in controlling the accumulation and distribution of arsenic and cadmium in plants, and possible strategies for manipulating sulfur metabolism to limit their accumulation in food crops.