Curcumin and Nano-Curcumin Mitigate Copper Neurotoxicity by Modulating Oxidative Stress, Inflammation, and Akt/GSK-3ß Signaling.

Copper (Cu) is essential for multiple biochemical processes, and copper sulphate (CuSO4) is a pesticide used for repelling pests. Accidental or intentional intoxication can induce multiorgan toxicity and could be fatal. Curcumin (CUR) is a potent antioxidant, but its poor systemic bioavailability is the main drawback in its therapeutic uses. This study investigated the protective effect of CUR and N-CUR on CuSO4-induced cerebral oxidative stress, inflammation, and apoptosis in rats, pointing to the possible involvement of Akt/GSK-3ß. Rats received 100 mg/kg CuSO4 and were concurrently treated with CUR or N-CUR for 7 days. Cu-administered rats exhibited a remarkable increase in cerebral malondialdehyde (MDA), NF-κB p65, TNF-α, and IL-6 associated with decreased GSH, SOD, and catalase. Cu provoked DNA fragmentation, upregulated BAX, caspase-3, and p53, and decreased BCL-2 in the brain of rats. N-CUR and CUR ameliorated MDA, NF-κB p65, and pro-inflammatory cytokines, downregulated pro-apoptotic genes, upregulated BCL-2, and enhanced antioxidants and DNA integrity. In addition, both N-CUR and CUR increased AKT Ser473 and GSK-3ß Ser9 phosphorylation in the brain of Cu-administered rats. In conclusion, N-CUR and CUR prevent Cu neurotoxicity by attenuating oxidative injury, inflammatory response, and apoptosis and upregulating AKT/GSK-3ß signaling. The neuroprotective effect of N-CUR was more potent than CUR.

Systemic toxicity eliciting metal ion levels from metallic implants and orthopedic devices - A mini review.

The metal/metal alloy-based implants and prostheses are in use for over a century, and the rejections, revisions, and metal particle-based toxicities were reported concurrently. Complications developed due to metal ions, metal debris, and organo-metallic particles in orthopedic patients have been a growing concern in recent years. It was reported that local and systemic toxicity caused by such released products from the implants is one of the major reasons for implant rejection and revision. Even though the description of environmental metal toxicants and safety limits for their exposure to humans were well established in the literature, an effort was not adequately performed in the case of implant-based metal toxicology. Since the metal ion concentration in serum acts as a possible indicator of the systemic toxicity, this review summarizes the reported human serum safe limits, toxic limits, and concentration range (µg/L, ppb, etc.) for mild to severe symptoms of six (cardiac, hepatic, neuro, nephron, dermal and endocrine) systemic toxicities for twelve most commonly used metallic implants. It also covers the widely used metal ion quantification techniques and systemic toxicity treatments reported.

Selenomethionine protects hematopoietic stem/progenitor cells against cobalt nanoparticles by stimulating antioxidant actions and DNA repair functions.

Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) can differentiate into all blood lineages to maintain hematopoiesis, wound healing, and immune functions. Recently, cobalt-chromium alloy casting implants have been used extensively in total hip replacements; however, cobalt nanoparticles (CoNPs) released from the alloy were toxic to HSCs and HPCs. We aimed to investigate the mechanism underlying the toxic effect of CoNPs on HSCs/HPCs and to determine the protective effect of selenomethionine (SeMet) against CoNPs in vitro and in vivo. Human and rat CD34+ HSCs/HPCs were isolated from cord blood and bone marrow, respectively. CoNPs decreased the viability of CD34+ HSCs/HPCs and increased apoptosis. SeMet attenuated the toxicity of CoNPs by enhancing the antioxidant ability of cells. The protective effect of SeMet was not completely abolished after adding H2O2 to abrogate the improvement of the antioxidant capacity by SeMet. SeMet and CoNPs stimulated ATM/ATR DNA damage response signals and inhibited cell proliferation. Unlike CoNPs, SeMet did not damage the DNA, and cell proliferation recovered after removing SeMet. SeMet inhibited the CoNP-induced upregulation of hypoxia inducible factor (HIF)-1α, thereby disrupting the inhibitory effect of HIF-1α on breast cancer type 1 susceptibility protein (BRCA1). Moreover, SeMet promoted BRCA1-mediated ubiquitination of cyclin B by upregulating UBE2K. Thus, SeMet enhanced cell cycle arrest and DNA repair post-CoNP exposure. Overall, SeMet protected CD34+ HSCs/HPCs against CoNPs by stimulating antioxidant activity and DNA repair.

Toxic metal exposure as a possible risk factor for COVID-19 and other respiratory infectious diseases.

Multiple medical, lifestyle, and environmental conditions, including smoking and particulate pollution, have been considered as risk factors for COronaVIrus Disease 2019 (COVID-19) susceptibility and severity. Taking into account the high level of toxic metals in both particulate matter (PM2.5) and tobacco smoke, the objective of this review is to discuss recent data on the role of heavy metal exposure in development of respiratory dysfunction, immunotoxicity, and severity of viral diseases in epidemiological and experimental studies, as to demonstrate the potential crossroads between heavy metal exposure and COVID-19 severity risk. The existing data demonstrate that As, Cd, Hg, and Pb exposure is associated with respiratory dysfunction and respiratory diseases (COPD, bronchitis). These observations corroborate laboratory findings on the role of heavy metal exposure in impaired mucociliary clearance, reduced barrier function, airway inflammation, oxidative stress, and apoptosis. The association between heavy metal exposure and severity of viral diseases, including influenza and respiratory syncytial virus has been also demonstrated. The latter may be considered a consequence of adverse effects of metal exposure on adaptive immunity. Therefore, reduction of toxic metal exposure may be considered as a potential tool for reducing susceptibility and severity of viral diseases affecting the respiratory system, including COVID-19.

Joint effects of cadmium and copper on Apis mellifera forgers and larvae.

Honey bees (Apis mellifera L.) are important ecological and agricultural resources. They are among the most widely available pollinators and provide products as well as services. Unfortunately, honey bee populations are susceptible to several environmental threats, including heavy metal exposure. Honey bees can be exposed to heavy metals when foraging on contaminated honey and pollen resources, and in some cases by airborne exposure. We studied the joint acute and chronic effects of cadmium (Cd) and copper (Cu) on A. mellifera. A 1:1 solution of the two heavy metals increased larval developmental duration and the mortality of both larvae and foragers in a dose-dependent way, decreased forager feeding, increased body metal burdens, and disrupted the sucrose response behavior of foragers. In combination, Cd and Cu demonstrated a weakly synergistic effect on foragers, but for larvae an initially antagonistic effect at low doses changed to strongly synergistic response at higher concentrations. The sucrose response threshold of foragers decreased significantly when they were dosed with increasing concentrations of the metal mixtures. Overall, the fitness of honey bee larvae and foragers is detrimentally affected when these metals co-occur.

Temperature elevation stage-specifically increases metal toxicity through bioconcentration and impairment of antioxidant defense systems in juvenile and adult marine mysids.

Metals are of serious concern due to their toxicity, persistency, and accumulation potential in aquatic animals. However, limited information is available on the combined effects of metal with temperature elevation, which is one of the future climate changes suggested for the oceans. In this study, the effect of temperature elevation was investigated by analyzing toxicity, bioconcentration, and antioxidant response in juvenile and adult marine mysids upon exposure to 20 °C and 25 °C for 48 h and 96 h. Based on LC50 values, toxicity of metals was highly reliant on temperature, exposure period, and age. Elevation in temperature significantly increased the whole metal toxicity in juveniles. Bioconcentration was elevated by increasing exposure period and metal concentration. Significant elevation of malondialdehyde (MDA) and depletion of glutathione (GSH) was measured in juveniles, while significant elevation of both MDA and GSH was detected in adults. Subsequently, enzymatic activities of antioxidant enzymes in catalase (CAT) and superoxide dismutase (SOD) increased significantly in adults at 48 h and 96 h, whereas most activities were significantly lowered in juveniles at 96 h. These results suggest that the early life stage of marine mysids is more sensitive to the combined effect of metal and temperature than adult stage due to an impairment in the induction of the antioxidant defense system.

Prevalence of geophagy and knowledge about its health effects among native Sub-Saharan Africa, Caribbean and South America healthy adults living in France.

Geophagy is widespread among women from Sub-Saharan Africa, South America and the Caribbean and may persist in western countries. This practice may be associated with adverse effects such as anaemia, constipation or intestinal occlusion. We aimed to determine the prevalence of geophagy and the level of knowledge about its health effects among healthy adults originating from these countries and attending a travel medicine and international vaccination consultation in France. Among 101 travellers enrolled in the study, 83 (82.1%) were born in Sub-Saharan Africa and 13 (12.8%) in South America or the Caribbean. The mean duration of residence in France was 15.6 ± 10.4 years. Previous or current geophagy was present in 42 travellers [previous geophagy in 31 (30.7%) and current consumption in 11 (10.9%)]; 38 (90.5%) were women. The rate of awareness of harmful effects of geophagy as the risk of iron-deficient anaemia (18.8%) and soil-transmitted intestinal parasitic infections (11.9%) was low overall. Women with previous or current geophagy more often had history of iron therapy compared to those who never consumed, both during pregnancy (50.0 versus 14.3%; p = 0.0009) and outside pregnancy (47.4 versus 2.8%; p < 0.0001). Despite a long period of residence in France, geophagy was still a current practice among 10.9% of Sub-Saharan, South American and Caribbean travellers, who are poorly informed of its harmful effects. Therefore, specific information tailored to Sub-Saharan, South American and Caribbean about the risks of geophagy should be implemented in western countries.Level of evidence Level V, descriptive cross-sectional survey.

Probiotic mitigates the toxic effects of potassium dichromate in a preclinical study: a randomized controlled trial.

BACKGROUND: The present study aimed to evaluate the nutritional, physiological and biochemical effects of dietary supplementation of an association of probiotic bacteria in rats intoxicated with chromium (VI). Ninety-six male rats, recently weaned, were randomly divided into eight groups (n = 12): Control, DK12, DK24 and DK36 (0, 0.12, 0.24 and 0.36 g kg-1 of K2 Cr2 O7 incorporated in the basal feed, respectively) and groups Prob, DK12 + Prob, DK24 + Prob and DK36 + Prob received a progressive dose of 0, 0.12, 0.24 and 0.36 g kg-1 of K2 Cr2 O7 incorporated in the basal feed and supplemented with 0.02 g kg-1 of an association of probiotic bacteria (Lactobacillus acidophilus, Enterococcus faecium, Bifidobacterium thermophilum and Bifidobacterium longum). RESULTS: After 90 days, we observed significant (P < 0.05) and dose-dependent alterations from incorporation of increasing doses of chromium (VI) related to nutritional, physiological and biochemical parameters. These changes were attenuated (P < 0.05) with probiotic supplementation. CONCLUSION: Supplementation with probiotics in the diet beneficially modified the nutritional and physiological parameters, as well as hepatic, renal, glycemic and lipid profiles, of animals intoxicated with increasing doses of K2 Cr2 O7 . © 2018 Society of Chemical Industry.

Ingestion of bedding material as a cause of acute copper sulfate poisoning in turkey poults.

The article reports a case of acute copper sulfate (CuSO4) poisoning in 2-day-old turkeys. The first incidences were noticed 2 h after placing the animals in the poultry house, where turkeys were provided with wood shaving bedding. Post-mortem examination showed wood shavings present in gastric and intestinal contents and numerous lesions in the alimentary tract: dark green color of the koilin lining, and surface erosions, deep ulceration, and severe congestion of the gizzard. The copper (Cu) concentration in samples of the liver, kidney, heart, gizzard content, gizzard muscle, gizzard lining, and wood shavings from the bedding was determined. Our results showed that the level of Cu in the livers of affected birds was more than sevenfold higher than the recommended value and the Cu content in bedding material was above the value considered to be toxic to turkeys. Our investigation identified the bedding disinfected using a CuSO4 solution as a possible cause of turkey fatalities.

Metallosis in cemented titanium alloy total knee arthroplasty without apparent metal-on-metal articulation.

BACKGROUND: Metallosis is an uncommon phenomenon observed in late failures of cemented total knee arthroplasty (TKA), and it is rarely seen in the absence of metal-on-metal articulation. METHODS: We report the case of a TKA patient with cemented titanium-alloy components and a polyethylene patella that was revised for early loosening with intra-operative severe metallosis. RESULTS: We found that loosening and severe metallosis were associated with methacrylate particle abrasion on titanium alloy surfaces. CONCLUSION: Serum titanium ion level measurement may be helpful in the workup of a painful TKA with titanium-alloy components in order to establish a diagnosis.

Spatial distribution, risk and potential sources of lead in soils in the vicinity of a historic industrial site.

Because of measures taken by local and national government agencies to control releases of metals, former industrial sites in China that are contaminated with lead (Pb) in soils have been abandoned. Compared with historic sites themselves, little attention has been paid to contamination with Pb in areas surrounding these sites. In this study, a method by integrating sequential extraction and isotopic fingerprinting was proposed to reveal the key fractions of Pb contaminants in soils, trace their sources and determine the subject of liability for remediation. Topsoils from near a historic site, where lead oxide was produced, were found to be contaminated. Concentrations of Pb in soils were inversely proportional to distances from the industrial site and depth in soils. The predominant form of Pb was the Fe/Mn-oxide-bound fraction (FM3), which accounted for from 53.39% to 82.07% of total concentrations of Pb. Concentrations of Pb in vegetables produced on contaminated soils exceeded those allowed in food for consumption by humans. An assessment of hazards and risks posed by consumption of vegetables grown on these soils indicated relatively high potential for adverse effects on local residents around the closed plant. By use of isotopic finger printing for Pb, the abandoned factory was determined to be the most likely source of Pb in topsoils, especially fraction FM3. To mitigate exposures of people to Pb via consumption of locally produced food, recommended strategies should target legacy sources of Pb to soils in the vicinity of this historic industrial site.

Environmental exposure to cadmium-a risk for health of the general population in industrialized countries and preventive strategies.

Cadmium (Cd) is a heavy metal belonging to the group of the main chemical pollutants of the natural and occupational environment in economically developed countries. The forecasts indicate that contamination of the environment with this toxic metal, and thus the exposure of the general population, will increase. Food (particularly plant products) is the main source of the general population exposure to this element. Moreover, an important, and often the main, source of intoxication with Cd is habitual tobacco smoking. Recent epidemiological studies have provided numerous evidence that even low-level environmental exposure to this toxic metal, nowadays occurring in numerous economically developed countries, creates a risk for health of the general population. The low-level lifetime exposure to this metal may lead to the damage to the kidneys, liver, skeletal system, and cardiovascular system, as well as to the deterioration of the sight and hearing. Moreover, it has been suggested that environmental exposure to this xenobiotic may contribute to the development of cancer of the lung, breast, prostate, pancreas, urinary bladder, and nasopharynx. Taking the above into account, the aim of this review article is to draw more attention to Cd as an environmental risk factor for the health of the general population and the need to undertake preventive actions allowing to reduce the risk of health damage due to a lifetime exposure to this toxic metal.

Genotoxicity of 11 heavy metals detected as food contaminants in two human cell lines.

Heavy metals, such as arsenic (As), antimony (Sb), barium (Ba), cadmium (Cd), cobalt (Co), germanium (Ge), lead (Pb), nickel (Ni), tellurium (Te), and vanadium (V) are widely distributed in the environment and in the food chain. Human exposure to heavy metals through water and food has been reported by different international agencies. Although some of these heavy metals are essential elements for human growth and development, they may also be toxic at low concentrations due to indirect mechanisms. In this study, the genotoxic and cytotoxic properties of 15 different oxidation statuses of 11 different heavy metals were investigated using high-throughput screening (γH2AX assay) in two human cell lines (HepG2 and LS-174T) representative of target organs (liver and colon) for food contaminants. Base on their lowest observed adverse effect concentration, the genotoxic potency of each heavy metal in each cell line was ranked in decreasing order, NaAsO2 > CdCl2 > PbCl2 (only in LS-174T cells) > As2 O5 > SbCl3 > K2 TeO3 > As2 O3 . No significant genotoxicity was observed with the other heavy metals tested. Cell viability data indicate that several heavy metals (As, Cd, Co, Ni, Sb, and Te) induce cytotoxicity at high concentrations, whereas an increase in the number of cells was observed for lead concentrations >100 µM in both cell lines tested, suggesting that lead stimulates cell growth. All these results highlight the possible human health hazards associated with the presence of heavy metals present in food. Environ. Mol. Mutagen. 59:202-210, 2018. © 2017 Wiley Periodicals, Inc.

Gut remediation: a potential approach to reducing chromium accumulation using Lactobacillus plantarum TW1-1.

Some lactobacilli have protective effects against some heavy metals in mammals, but the underlying mechanism is not fully understood. To evaluate the remediation potency and the mechanism of Lactobacillus against chromium (Cr) in mice, Lactobacillus plantarum TW1-1 was orally administrated to Kunming mice for 7 weeks during exposure to 1 mM K2Cr2O7 in drinking water. Results showed that TW1-1 helped to decrease Cr accumulation in tissues and increase Cr excretion in feces, and may also attenuate alterations in oxidative stress and histopathological changes caused by Cr exposure. Moreover, the chromate reduction ability of fecal bacteria doubled after administration of TW1-1 upon Cr induction. MiSeq sequencing of fecal bacterial 16S rRNA genes revealed that the overall structures of gut microbiota was shifted by Cr exposure and partially restored by TW1-1. The abundances of 49 of the 79 operational taxonomic units altered by Cr were reversed by TW1-1. Based on these, we proposed a working model of TW1-1 against Cr: TW1-1 helps to remove Cr from the host and meanwhile acts as a regulator of gut microbiota, which aids in chromate reduction and provide protection against Cr. We call this process of remediation of heavy metal in the gut "gut remediation".

Effects of Nano-zinc on Biochemical Parameters in Cadmium-Exposed Rats.

Cadmium (Cd) is a toxic environmental and occupational pollutant with reported toxic effects on the kidneys, liver, lungs, bones, and the immunity system. Based on its physicochemical similarity to cadmium, zinc (Zn) shows protective effects against cadmium toxicity and cadmium accumulation in the body. Nano-zinc and nano-zinc oxide (ZnO), recently used in foods and pharmaceutical products, can release a great amount of Zn2+ in their environment. This research was carried out to investigate the more potent properties of the metal zinc among sub-acute cadmium intoxicated rats. Seventy-five male Wistar rats were caged in 15 groups. Cadmium chloride (CdCl2) was used in drinking water to induce cadmium toxicity. Different sizes (15, 20, and 30 nm) and doses of nano-zinc particles (3, 10, 100 mg/kg body weight [bw]) were administered solely and simultaneously with CdCl2 (2-5 mg/kg bw) for 28 days. The experimental animals were decapitated, and the biochemical biomarkers (enzymatic and non-enzymatic) were determined in their serum after oral exposure to nano-zinc and cadmium. Statistical analysis was carried out with a one-way ANOVA and t test. P < 0.05 was considered as statistically significant. The haematocrit (HCT) significantly increased and blood coagulation time significantly reduced in the nano-zinc-treated rats. AST, ALT, triglyceride, total cholesterol, LDL, and free fatty acids increased significantly in the cadmium- and nano-zinc-treated rats compared with the controls. However, albumin, total protein, and HDLc significantly decreased in the cadmium- and nano-zinc-treated rats compared with the controls (P < 0.05). It seems that in the oral administration of nano-zinc, the smaller sizes with low doses and the larger sizes with high doses are more toxic than metallic zinc. In a few cases, an inverse dose-dependent relationship was seen as well. This research showed that in spite of larger sizes of zinc, smaller sizes of nano-zinc particles are not suitable for protection against cadmium intoxication.

Do Dietary Habits Influence Trace Elements Release from Fixed Orthodontic Appliances?

The objective was to investigate the effect of dietary habits on the release of Cr and Ni ions from orthodontic appliances by hair mineral analysis. Patients (N = 47) underwent electronic questionnaire survey to investigate the effect of dietary habits on Cr and Ni levels in hair. The research was carried out on hair sampled at the beginning and in the 4th, 8th, and 12th months of the treatment. The content of Cr and Ni in the collected samples was determined by ICP-OES. The study showed that consumption of acidic dietary products may have the effect on increasing the release of Cr and Ni ions from orthodontic appliances. The release of Cr from orthodontic appliances in patients who consumed fruit juice, coffee, yoghurt, and vinegar was higher. The coefficients enabling comparison of metal ions release pattern at a given sampling points were defined. The comparison of the coefficients yielded the information on the possible magnification of metal ions released as the result of the additional factor consumption of acidic food or drink that intensifies metal ions release. The following magnification pattern was found for chromium: coffee (7.57 times) > yoghurt (2.53) > juice (1.86) > vinegar (1.08), and for nickel: vinegar (2.2) > coffee (1.22) > juice (1.05). Yoghurt did not intensify the release of nickel. Concluding, orthodontic patients should avoid drinking/eating coffee, yoghurt, fruit juices, and vinegar.

Attenuating Effect of Zinc and Vitamin E on the Intestinal Oxidative Stress Induced by Silver Nanoparticles in Broiler Chickens.

Silver nanoparticles (AgNPs) have been increasingly used as antimicrobial and disinfectant. However, intestinal model studies have shown that AgNPs induce oxidative stress. Hence, this study aims to investigate the effects of dietary supplemental zinc (Zn) and vitamin E (VE; α-tocopherol acetate) on attenuating AgNP-induced intestinal oxidative stress in broiler chickens. The chickens were divided into two groups as follows: (1) control group fed with a corn-soybean meal basal diet and (2) nano group, received drinking water containing 1000 mg/kg AgNPs. All the nano-exposed birds were divided into six dietary treatment groups, namely, the basal diets supplemented with (1) 60 mg/kg Zn as ZnSO4, (2) 120 mg/kg Zn, (3) 100 mg/kg VE, (4) 200 mg/kg VE, (5) 60 mg/kg Zn and 100 mg/kg VE, and (6) 120 mg/kg Zn and 200 mg/kg VE. Results showed that the AgNPs significantly reduced the body weights of the broilers after 42 days of oral administration of AgNPs (P < 0.05), and this effect was not alleviated by any of the dietary treatments. The activity of superoxide dismutase (CuZn-SOD) increased in all the AgNP-treated birds (P < 0.05); however, CuZn-SOD did not increase in birds fed with basal diet supplemented with 200 mg/kg VE. In this treatment, the VE exerted an antioxidant effect to prevent the activation of the CuZn-SOD enzyme. Furthermore, supplementing Zn increased the activities of catalase and glutathione peroxidase in the jejunal mucosa (P < 0.05), which were accompanied with increased malondialdehyde levels (P < 0.05) in the broilers. AgNP exposure resulted in a significant messenger RNA (mRNA) upregulation of toll-like receptor 4 (TLR4) and TLR2-1 in the jejunal mucosa (P < 0.05). However, supplemental ZnVE did not reduce TLRs' mRNA expression, except for the diminished TLR2-1 mRNA levels in birds fed with basal diet supplemented with 120 mg/kg Zn and 200 mg/kg VE. We concluded that although dietary Zn and VE supplementation did not attenuate growth depression effect of AgNP, it however attenuates intestinal oxidative stress in AgNP-treated broiler chickens.