Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

Pb, As and Mn are neurotoxic metals, present as mixtures at various settings. All metals are known to interfere with cholinergic/dopaminergic neurotransmission and motor function. The main objective of this work was to assess metal mixture effects of lead (Pb), arsenic (As) and manganese (Mn) on motor activity, and to evaluate the role of each mixture component as well as their additive/synergic interactions on dopaminergic and cholinergic neurotransmission.

Lead, Arsenic, and Manganese Metal Mixture Exposures: Focus on Biomarkers of Effect.

The increasing exposure of human populations to excessive levels of metals continues to represent a matter of public health concern. Several biomarkers have been studied and proposed for the detection of adverse health effects induced by lead (Pb), arsenic (As), and manganese (Mn); however, these studies have relied on exposures to each single metal, which fails to replicate real-life exposure scenarios. These three metals are commonly detected in different environmental, occupational, and food contexts and they share common neurotoxic effects, which are progressive and once clinically apparent may be irreversible.

Bottled water: analysis of mycotoxins by LC-MS/MS.

The presence of mycotoxins in food samples has been widely studied as well as its impact in human health, however, information about its distribution in the environment is scarce. An analytical method comprising a solid phase extraction procedure followed by liquid chromatography tandem mass spectrometry analysis was implemented and validated for the trace analysis of mycotoxins in drinking bottled waters. Limits of quantification achieved for the method were between 0.

Changes in rat urinary porphyrin profiles predict the magnitude of the neurotoxic effects induced by a mixture of lead, arsenic and manganese.

The neurotoxic metals lead (Pb), arsenic (As) and manganese (Mn) are ubiquitous contaminants occurring as mixtures in environmental settings. The three metals may interfere with enzymes of the heme bioshyntetic pathway, leading to excessive porphyrin accumulation, which per se may trigger neurotoxicity. Given the multi-mechanisms associated with metal toxicity, we posited that a single biomarker is unlikely to predict neurotoxicity that is induced by a mixture of metals.

Role of N-acetylcysteine in protecting against 2,5-hexanedione neurotoxicity in a rat model: changes in urinary pyrroles levels and motor activity performance.

The interference of N-acetylcysteine (NAC) on 2,5-hexanedione (2,5-HD) neurotoxicity was evaluated through behavioral assays and the analysis of urinary 2,5-HD, dimethylpyrrole norleucine (DMPN), and cysteine-pyrrole conjugate (DMPN NAC), by ESI-LC-MS/MS, in rats exposed to 2,5-HD and co-exposed to 2,5-HD and NAC. Wistar rats were treated with 4 doses of: 400mg 2,5-HD/kg bw (group I), 400mg 2,5-HD/kg bw+200mg NAC/kg bw (group II), 200mg NAC/kg bw (group III) and with saline (group IV). The results show a significant decrease (p<0.

Arsenic and manganese alter lead deposition in the rat.

Lead (Pb) continues to be a major toxic metal in the environment. Pb exposure frequently occurs in the presence of other metals, such as arsenic (As) and manganese (Mn). Continued exposure to low levels of these metals may lead to long-term toxic effects due to their accumulation in several organs.

Alternative biomarkers of n-hexane exposure: characterization of aminoderived pyrroles and thiol-pyrrole conjugates in urine of rats exposed to 2,5-hexanedione.

The identification of pyrrole derivatives in urine of rats exposed to 2,5-hexanedione (2,5-HD), was performed to select an adequate peripheral biomarker predictive of 2,5-HD neurotoxicity. Studies on molecular mechanism of 2,5-HD neurotoxicity have revealed that 2,5-hexanedione reacts with free amino groups of lysine in proteins forming primary pyrrole adducts, which may autoxidize and form pyrrole dimers, responsible for protein crosslinking in neurofilaments, or react with sulfhydryl groups of cysteine in peptides and proteins, forming secondary pyrrole adducts, which probably may inhibit the process responsible by 2,5-HD neurotoxicity. In this work, the analysis of excreted 2,5-HD and pyr-role derivatives in urine of rats i.

Evaluation of neurobehavioral and neuroinflammatory end-points in the post-exposure period in rats sub-acutely exposed to manganese.

Manganese (Mn) can cause manganism, a neurological disorder similar to Parkinson' Disease (PD). The neurobehavioral and neuroinflammatory end-points in the Mn post exposure period have not been studied yet. Rats were injected on alternate days with 8 doses of MnCl2 (25mg/kg) or saline, then euthanized 1, 10, 30 or 70 days following the last dose.

Urinary delta-ALA: a potential biomarker of exposure and neurotoxic effect in rats co-treated with a mixture of lead, arsenic and manganese.

Lead (Pb), arsenic (As) and manganese (Mn) are neurotoxic elements that often occur in mixtures for which practically no information is available on biomarkers (BMs) for the evaluation of exposure/effects. Exposures to these metals may increase delta-aminolevulinic acid (delta-ALA), which in itself may potentiate neurotoxicity. The objective of this study was to investigate the utility of urinary delta-ALA (delta-ALA-U) levels as BM of exposure and/or neurotoxic effects induced by this mixture.

Comparison between 5-aminosalicylic acid (5-ASA) and para-aminosalicylic acid (4-PAS) as potential protectors against Mn-induced neurotoxicity.

Manganese (Mn) is an essential metal for biological systems; however, occupational or clinical exposure to high levels of Mn can produce a neurological disorder called manganism. Oxidative stress and neuroinflammation play major roles in the Mn-induced neurodegeneration leading to dysfunction of the basal ganglia. We investigated the toxic effects of MnCl2 in an immortalized rat brain endothelial cell line (RBE4) and the protective effects of the radical scavenging aminosalicylic acids, 5-aminosalicylic acid (5-ASA) and 4-aminosalicylic acid (4-PAS).

Manganese alters rat brain amino acids levels.

Manganese (Mn) is an essential element and it acts as a cofactor for a number of enzymatic reactions, including those involved in amino acid, lipid, protein, and carbohydrate metabolism. Excessive exposure to Mn can lead to poisoning, characterized by psychiatric disturbances and an extrapyramidal disorder. Mn-induced neuronal degeneration is associated with alterations in amino acids metabolism.

Protective effects of ebselen (Ebs) and para-aminosalicylic acid (PAS) against manganese (Mn)-induced neurotoxicity.

Chronic, excessive exposure to manganese (Mn) may induce neurotoxicity and cause an irreversible brain disease, referred to as manganism. Efficacious therapies for the treatment of Mn are lacking, mandating the development of new interventions. The purpose of the present study was to investigate the efficacy of ebselen (Ebs) and para-aminosalicylic acid (PAS) in attenuating the neurotoxic effects of Mn in an in vivo rat model.

The inhibitory effect of manganese on acetylcholinesterase activity enhances oxidative stress and neuroinflammation in the rat brain.

Background: Manganese (Mn) is a naturally occurring element and an essential nutrient for humans and animals. However, exposure to high levels of Mn may cause neurotoxic effects. The pathological mechanisms associated with Mn neurotoxicity are poorly understood, but several reports have established it is mediated, at least in part, by oxidative stress.

Prolactin is a peripheral marker of manganese neurotoxicity.

Unlabelled: Excessive exposure to Mn induces neurotoxicity, referred to as manganism. Exposure assessment relies on Mn blood and urine analyses, both of which show poor correlation to exposure. Accordingly, there is a critical need for better surrogate biomarkers of Mn exposure.

Microcystin-LR activates the ERK1/2 kinases and stimulates the proliferation of the monkey kidney-derived cell line Vero-E6.

Microcystin-LR (MCLR) is a peptide produced by freshwater cyanobacteria that induces severe hepatotoxicity in humans and animals. MCLR is also a potent tumour promoter and it has been proposed that this activity is mediated by the inhibition of protein phosphatases PP1/PP2A, possibly through the activation of proto-oncogenes c-jun, c-fos and c-myc. However, the mechanisms underlying MCLR-induced tumour promotion are still largely unknown, particularly in non-liver cells.

Rat brain endothelial cells are a target of manganese toxicity.

Manganese (Mn) is an essential trace metal; however, exposure to high Mn levels can result in neurodegenerative changes resembling Parkinson's disease (PD). Information on Mn's effects on endothelial cells of the blood-brain barrier (BBB) is lacking. Accordingly, we tested the hypothesis that BBB endothelial cells are a primary target for Mn-induced neurotoxicity.

Comparative study of the cytotoxic effect of microcistin-LR and purified extracts from Microcystis aeruginosa on a kidney cell line.

Microcystin-LR (MCLR) is a potent hepatotoxin, but increasing evidences suggest that it might also induce kidney injury. The aim of this work was to evaluate the cytotoxicity of MCLR on a kidney cell line (Vero-E6). Cells were exposed for up to 72 h either to Microcystis aeruginosa extracts from both MCLR-producer and non-MCLR-producer isolates or to pure MCLR (1.

Morphological and ultrastructural effects of microcystin-LR from Microcystis aeruginosa extract on a kidney cell line.

The aim of this study was to examine the toxic effects of a microcystin-LR (MCLR)-containing cyanobacteria extract on the subcellular organization of a kidney cell line (Vero-E6). Cells were exposed to different MCLR concentrations (1.3-150 microM) for 24, 48 and 72h and two cytotoxicity assays were performed.

Antioxidants prevent the cytotoxicity of manganese in RBE4 cells.

Manganese (Mn) is an essential trace element required for ubiquitous enzymatic reactions. Chronic overexposure to this metal may, however, promote potent neurotoxic effects. The mechanism of Mn toxicity is not well established, but several studies indicate that oxidative stress and mitochondria play major roles in the Mn-induced neurodegenerative processes that lead to dysfunction in the basal ganglia.

High-fish consumption and risk prevention: assessment of exposure to methylmercury in Portugal.

The aim of this study was to evaluate the exposure to methylmercury (MeHg) of potential populations at risk living in Portugal. To ascertain youth exposure, a questionnaire was distributed to 300 students of a middle secondary school in Sesimbra and to 429 students studying in Canecas, selected as the control population. The average number of fish meals consumed by person was 4.

Biomarkers of exposure and effect as indicators of the interference of selenomethionine on methylmercury toxicity.

The present study was conducted to clarify the interference of selenomethionine (SeMet) on methylmercury (MeHg) toxicity through the evaluation of changes in biomarkers of exposure and effect in rats exposed to MeHg and co-exposed to MeHg and SeMet. Male Wistar rats received two intraperitoneally (i.p.

Lipoperoxidation products and thiol antioxidants in chromium exposed workers.

Hexavalent chromium is an established carcinogenic agent, which is not directly reactive with DNA. Its genotoxicity involves a reduction step, producing reactive oxygen species and radicals, and also lower valence forms which form stable complexes with intracellular macromolecules. The trivalent form of chromium may directly react with the genetic material and has also been shown to generate oxidative damage in vitro.

Risk of human exposure to paralytic toxins of algal origin.

The most significant neurotoxins produced by harmful algal blooms (HABs) are paralytic shellfish toxins (PSTs) found in shellfish and freshwater. Human exposure to neurotoxins through the food consumption represents a severe hazard to human health and the exposure through contaminated water represents an added risk often difficult to recognize. Furthermore, there is an insufficient knowledge of toxicokinetics of these complex toxins produced by HABs.

Evidence of zinc protection against 2,5-hexanedione neurotoxicity: correlation of neurobehavioral testing with biomarkers of excretion.

Risk prevention of human exposure against n-hexane neurotoxicity is relevant towards the protective measures to be proposed in occupational toxicology. Metabolic studies have identified 2,5-hexanedione (2,5-HD) as the main neurotoxic metabolite of n-hexane, which reacts with amino groups of lysine in axonal neurofilaments forming 2,5-dimethylpyrrole adducts, which are responsible for n-hexane neurotoxicity. In the present study, we have investigated the interaction of zinc with 2,5-HD, by correlating the decrease of pyrrole derivatives excretion with changes of neurobehavioral effects.

Elevated levels of DNA-protein crosslinks and micronuclei in peripheral lymphocytes of tannery workers exposed to trivalent chromium.

DNA-protein crosslinks (DPC) are a promising biomarker of exposure to hexavalent chromium, a known human carcinogen. Although trivalent chromium is considered to have much lower toxicity, the risk involved in chronic exposure is uncertain. DPC may be a useful tool in clarifying this risk, by signaling an exposure of body tissues to biologically active forms of chromium.