Search

Methylmercury (MeHg) is a global environmental pollutant with neurotoxic effects. Exposure to MeHg via consumption of seafood and fish can severely impact fetal neurobehavioral development even when MeHg levels in maternal blood are as low as about 5 μg/L, which the mother tolerates well. Persistent motor dysfunctions and cognitive deficits may result from trans-placental exposure. The present review summarizes current knowledge on the mechanisms of MeHg toxicity during the period of nervous system development. Although cerebellar Purkinje cells are MeHg targets, the actions of MeHg on thiol components in the neuronal cytoskeleton as well as on mitochondrial enzymes and induction of disturbances of glutamate signaling can impair extra-cerebellar functions, also at levels well tolerated by adult individuals. Numerous herbal substances possess neuroprotective effects, predominantly represented by natural polyphenolic molecules that might be utilized to develop natural drugs to alleviate neurotoxicity symptoms caused by MeHg or other Hg compounds., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mercury (Hg) is widely recognized as a neurotoxic metal, besides it can also act as a proinflammatory agent and immunostimulant, depending on individual exposure and susceptibility. Mercury exposure may arise from internal body pathways, such as via dental amalgams, preservatives in drugs and vaccines, and seafood consumption, or even from external pathways, i.e., occupational exposure, environmental pollution, and handling of metallic items and cosmetics containing Hg. In susceptible individuals, chronic low Hg exposure may trigger local and systemic inflammation, even exacerbating the already existing autoimmune response in patients with autoimmunity. Mercury exposure can trigger dysfunction of the autoimmune responses and aggravate immunotoxic effects associated with elevated serum autoantibodies titers. The purpose of the present review is to provide a critical overview of the many issues associated with Hg exposure and autoimmunity. In addition, the paper focuses on individual susceptibility and other health effects of Hg., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Mercury (Hg), a highly toxic environmental pollutant, shows harmfulness which still represents a big concern for human health, including hazards to fertility and pregnancy outcome. Research has shown that Hg could induce impairments in the reproductive function, cellular deformation of the Leydig cells and the seminiferous tubules, and testicular degeneration as well as abnormal menstrual cycles. Some studies investigated spontaneous abortion and complicated fertility outcome due to occupational Hg exposure. Moreover, there is a relation between inhaled Hg vapour and reproductive outcome. This MiniReview evaluates the hypothesis that exposure to Hg may increase the risk of reduced fertility, spontaneous abortion and congenital deficits or abnormalities., (© 2019 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Mercury (Hg), which is a non-essential element, is considered a highly toxic pollutant for biological systems even when present at trace levels. Elevated Hg exposure with the growing release of atmospheric pollutant Hg and rising accumulations of mono-methylmercury (highly neurotoxic) in seafood products have increased its toxic potential for humans. This review aims to highlight the potential relationship between Hg exposure and Alzheimer's disease (AD), based on the existing literature in the field. Recent reports have hypothesized that Hg exposure could increase the potential risk of developing AD. Also, AD is known as a complex neurological disorder with increased amounts of both extracellular neuritic plaques and intracellular neurofibrillary tangles, which may also be related to lifestyle and genetic variables. Research reports on AD and relationships between Hg and AD indicate that neurotransmitters such as serotonin, acetylcholine, dopamine, norepinephrine, and glutamate are dysregulated in patients with AD. Many researchers have suggested that AD patients should be evaluated for Hg exposure and toxicity. Some authors suggest further exploration of the Hg concentrations in AD patients. Dysfunctional signaling pathways in AD and Hg exposure appear to be interlinked with some driving factors such as arachidonic acid, homocysteine, dehydroepiandrosterone (DHEA) sulfate, hydrogen peroxide, glucosamine glycans, glutathione, acetyl-L carnitine, melatonin, and HDL. This evidence suggests the need for a better understanding of the relationship between AD and Hg exposure, and potential mechanisms underlying the effects of Hg exposure on regional brain functions. Also, further studies evaluating brain functions are needed to explore the long-term effects of subclinical and untreated Hg toxicity on the brain function of AD patients.

Histamine is one of the most important health issues associated with consumption of canned tuna because of possible allergic and anaphylactic reactions in consumers. Although the concentrations of histamine in tuna in Iran have been investigated in several studies, definitive conclusions are elusive. This study was undertaken as a systematic review and meta-analysis of the concentration and prevalence of histamine in Iranian canned tuna, and the related health risk was assessed. An extensive search of articles in the databases Scopus, PubMed, and Scientific Information Database resulted in 11 articles and a total of 693 samples for inclusion in this review. The minimum and maximum concentrations of histamine were determined as 8.59 ± 14.24 and 160.52 ± 87.59 mg kg −1 , respectively. The mean concentration was calculated as 77.86 mg kg −1 (95% confidence interval [CI], 47.51 to 108.21 mg kg −1 ), which was lower than the 200 mg kg −1 recommended limit by the U.S. Food and Drug Administration (FDA). The mean prevalence of histamine was 9.19% (95%; CI, 6.88 to 11.5%). The 95% value of the target hazard quotient for adult consumers was calculated as 0.10. In all studies performed in Iran, the concentration of histamine in canned tuna was lower than FDA standard. Health risk assessment indicated low histamine risk (target hazard quotient < 1) for adults in Iran from consumption of canned tuna.

Based on toxicological, clinical, and epidemiological knowledge, the present paper reviews the status regarding possible deleterious health effects from occupational exposure to metallic mercury (Hg) in dental practice. Symptoms from the central nervous system are among the health problems that most often are attributed to Hg exposure in dentists and dental nurses working with amalgam. Uncharacteristic symptoms of chronic low-level Hg vapor exposure including weakness, fatigue, and anorexia have been observed in numerous studies of dental personnel. It is crucial to protect both human health and the environment against negative effects of Hg. In line with this, the use of dental amalgam in industrial countries is about to be phased out. In Norway and Sweden, the use of the filling material is banned., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Historically, entities with a vested interest in a product that critics have suggested is harmful have consistently used research to back their claims that the product is safe. Prominent examples are: tobacco, lead, bisphenol A, and atrazine. Research literature indicates that about 80-90% of studies with industry affiliation found no harm from the product, while only about 10-20% of studies without industry affiliation found no harm. In parallel to other historical debates, recent studies examining a possible relationship between mercury (Hg) exposure and autism spectrum disorder (ASD) show a similar dichotomy. Studies sponsored and supported by industry or entities with an apparent conflict of interest have most often shown no evidence of harm or no "consistent" evidence of harm, while studies without such affiliations report positive evidence of a Hg/autism association. The potentially causal relationship between Hg exposure and ASD differs from other toxic products since there is a broad coalition of entities for whom a conflict of interest arises. These include influential governmental public health entities, the pharmaceutical industry, and even the coal burning industry. This review includes a systematic literature search of original studies on the potential relationship between Hg and ASD from 1999 to August 2015, finding that of the studies with public health and/or industry affiliation, 86% reported no relationship between Hg and ASD. However, among studies without public health and/or industry affiliation, only 21% find no relationship between Hg and ASD. The discrepancy in these results suggests a bias indicative of a conflict of interest.

Mercury (Hg) is a persistent bio-accumulative toxic metal with unique physicochemical properties of public health concern since their natural and anthropogenic diffusions still induce high risk to human and environmental health. The goal of this review was to analyze scientific literature evaluating the role of global concerns over Hg exposure due to human exposure to ingestion of contaminated seafood (methyl-Hg) as well as elemental Hg levels of dental amalgam fillings (metallic Hg), vaccines (ethyl-Hg) and contaminated water and air (Hg chloride). Mercury has been recognized as a neurotoxicant as well as immunotoxic and designated by the World Health Organization as one of the ten most dangerous chemicals to public health. It has been shown that the half-life of inorganic Hg in human brains is several years to several decades. Mercury occurs in the environment under different chemical forms as elemental Hg (metallic), inorganic and organic Hg. Despite the raising understanding of the Hg toxicokinetics, there is still fully justified to further explore the emerging theories about its bioavailability and adverse effects in humans. In this review, we describe current research and emerging trends in Hg toxicity with the purpose of providing up-to-date information for a better understanding of the kinetics of this metal, presenting comprehensive knowledge on published data analyzing its metabolism, interaction with other metals, distribution, internal doses and targets, and reservoir organs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can cause significant social, communication and behavioral challenges. Environmental contribution to ASD is due in large part to the sensitivity of the developing brain to external exposures such as lead (Pb), and mercury (Hg) as toxic heavy metals or due to a poor detoxification ability as the phenotype of this disorder. Selenium (Se) as an antioxidant element that counteracts the neurotoxicity of Hg, and Pb, presumably through the formation of nontoxic complexes. In the present study, Pb, Hg, and Se were measured in red blood cells (RBCs) of 35 children with ASD and 30 age- and gender-matched healthy control children using atomic absorption spectrometry. Receiver Operating Characteristics (ROC) analysis of the obtained data was performed to measure the predictive value of their absolute and relative concentrations. The obtained data demonstrates a significant elevation of Hg and Pb together with a significant decrease in the Se levels in RBCs of patients with ASD when compared to the healthy controls. The ratios of Se to both Pb and Hg were remarkably altered, being indicative of heavy metal neurotoxicity in patients with ASD. In conclusion, the present study indicates the importance of Se for prevention and/or therapy of heavy metal neurotoxicity.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that affects social, communication, and behavioral development. Recent evidence supported but also questioned the hypothetical role of compounds containing mercury (Hg) as contributors to the development of ASD. Specific alterations in the urinary excretion of porphyrin-containing ring catabolites have been associated with exposure to Hg in ASD patients. In the present study, the level of urinary porphyrins, as biomarkers of Hg toxicity in children with ASD, was evaluated, and its correlation with severity of the autistic behavior further explored. A total of 100 children was enrolled in the present study. They were classified into three groups: children with ASD (40), healthy controls (40), and healthy siblings of the ASD children (20). Children with ASD were diagnosed using DSM-IV-TR, ADI-R, and CARS tests. Urinary porphyrins were evaluated within the three groups using high-performance liquid chromatography (HPLC), after plasma evaluation of mercury (Hg) and lead (Pb) in the same groups. Results showed that children with ASD had significantly higher levels of Hg, Pb, and the porphyrins pentacarboxyporphyrin, coproporphyrin, precoproporphyrin, uroporphyrins, and hexacarboxyporphyrin compared to healthy controls and healthy siblings of the ASD children. However, there was no significant statistical difference in the level of heptacarboxyporphyrin among the three groups, while a significant positive correlation between the levels of coproporphyrin and precoproporphyrin and autism severity was observed. Mothers of ASD children showed a higher percentage of dental amalgam restorations compared to the mothers of healthy controls suggesting that high Hg levels in children with ASD may relate to the increased exposure to Hg from maternal dental amalgam during pregnancy and lactation. The results showed that the ASD children in the present study had increased blood Hg and Pb levels compared with healthy control children indicating that disordered porphyrin metabolism might interfere with the pathology associated with the autistic neurologic phenotype. The present study indicates that coproporphyrin and precoproporhyrin may be utilized as possible biomarkers for heavy metal exposure and autism severity in children with ASD.

Tachykinins (substance P, neurokinin A, and neurokinin B) are pro-inflammatory neuropeptides that may play an important role in some autoimmune neuroinflammatory diseases, including autism spectrum disorder (ASD). Mercury (Hg) is a neurotoxicant, and potentially one of the main environmental triggers for ASD as it induces neuroinflammation with a subsequent release of neuropeptides. This is the first study to explore the potentially causal relationship between levels of serum neurokinin A and blood mercury (BHg) in children with ASD. Levels of serum neurokinin A and BHg were measured in 84 children with ASD, aged between 3 and 10 years, and 84 healthy-matched children. There was a positive linear relationship between the Childhood Autism Rating Scale (CARS) and both serum neurokinin A and BHg. ASD children had significantly higher levels of serum neurokinin A than healthy controls (P < 0.001). Increased levels of serum neurokinin A and BHg were respectively found in 54.8 % and 42.9 % of the two groups. There was significant and positive linear relationship between levels of serum neurokinin A and BHg in children with moderate and severe ASD, but not in healthy control children. It was found that 78.3 % of the ASD patients with increased serum levels of neurokinin A had elevated BHg levels (P < 0.001). Neuroinflammation, with increased levels of neurokinin A, is seen in some children with ASD, and may be caused by elevated BHg levels. Further research is recommended to determine the pathogenic role of increased levels of serum neurokinin A and BHg in ASD. The therapeutic role of tachykinin receptor antagonists, a potential new class of anti-inflammatory medications, and Hg chelators, should also be studied in ASD.

The incidence of both obesity and autism spectrum disorders (ASD) has dramatically increased during the last decades. Moreover, the most recent studies have revealed increased risk of ASD in offspring of overweight and obese women. However, the mechanisms of association between ASD and maternal obesity are unknown. Taking into account the existing data indicating the association between mercury (Hg) exposure and development of obesity and ASD, we hypothesize that Hg may serve as an additional link between maternal obesity and ASD. In particular, it is supposed that obesity is associated with excessive accumulation of Hg in the maternal organism. After conception, the fetus is developing in the conditions of Hg overload within the body of obese women thus predisposing to the development of ASD. The proposed hypothesis may be confirmed by the existing data. In particular, previous studies demonstrated that overweight and obese persons are characterized by a significantly higher level of Hg in hair, blood and urine than the lean ones. Therefore, an obese organism is characterized by elevated Hg burden that may be transferred to the fetus during pregnancy. Moreover, multiple studies have demonstrated a tight association between maternal and children Hg status being indicative of placental transfer of metal from maternal organism to offspring. Finally, a growing body of data indicates the influence of Hg exposure and Hg status on the risk of ASD in children. However, additional experimental and clinical studies are required to prove the hypothesis and provide novel data on the role of Hg in maternal obesity-associated ASD development. In particular, the contribution of Hg to ASD development in children from obese mothers should be determined. If a significant role of Hg in maternal obesity ASD risk will be confirmed, this will open additional perspectives of risk modification. Taking into account the universal mechanisms of Hg toxicity, transport, and accumulation, further preventive actions may be undertaken to reduce the risk of Hg toxicity and Hg-associated ASD development. In particular, it is supposed that the use of Hg chelators (like N,N'bis-(2-mercaptoethyl)isophthalamide, NMBI), antioxidants, and anti-inflammatory compounds prior or during pregnancy may have a beneficial effect. However, the safety of such actions should repeatedly be tested to avoid adverse health effects in a developing fetus., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Selenium (Se) is an essential trace element for humans. It is found in the enzyme glutathione peroxidase. This enzyme protects the organism against certain types of damage. Some data suggest that Se plays a role in the body's metabolism of mercury (Hg). Selenium has in some studies been found to reduce the toxicity of Hg salts. Selenium and Hg bind in the body to each other. It is not totally clear what impact the amount of Se has in the human body on the metabolism and toxicity of prolonged Hg exposure.

Alpha lipoic acid (α-LA) and its reduced form dihydrolipoic acid (DHLA) have been historically considered as excellent anti-oxidants and oxidative stress scavengers. Upon oxidation with reactive oxygen species (ROS) and pro-oxidants, α-LA may be reconstituted from DHLA and other reduced forms. Oxidative stress is one of the fundamental causes of functional degeneration, autophagy and apoptosis leading to cytotoxicity and loss of cell survival, often due to exposure to xenobiotics, pollutants, heavy metals, and other environmental and endogenous toxicants. α-LA and DHLA can react with these molecules to strengthen the primary antioxidant defense system during cell injury. The compound α-LA is suggested for heavy metal detoxification, in particular for supporting the mercury (Hg) detoxifying process. Mercury is one of the major environmental toxicant, particularly noxious even upon limited exposure. Oxidative stress pathways have been identified as a key upstream event for Hg-induced toxicity in humans and animals. However, very few existing drugs to date can successfully prevent or reduce Hg toxicity. Although several thiol-based chelators, such as British Anti-Lewisite (2,3-dimercaptopropanol, BAL), meso-2,3-dimercaptosuccinic acid (DMSA), and sodium 2,3-dimercapto-1-propanesulfonate (DMPS), have shown promise for ameliorating Hg intoxication. In this review, the potential role of α-LA and DHLA in scavenging toxic metals and other xenobiotics is discussed, focusing especially on the mechanisms of actions of α-LA and DHLA as potential antioxidants towards Hg-induced toxicity. Unlabelled Image • Alpha-lipoic (ALA) and dihydrolipoic acid (DHLA) are useful detoxifying drug metabolites. • As cofactors, ALA and DHLA have a central function in the mitochondrial energy metabolism. • ALA and DHLA can increase the excretion of methylmercury from cells. • They are natural substances that can mimic and replace synthetic chelators. [ABSTRACT FROM AUTHOR]

Numerous studies have reported neurobehavioural effects in dental personnel occupationally exposed to chronic low levels of mercury (Hg). Hg exposure from dental work may also induce various chronic conditions such as elevation of amyloid protein expression, deterioration of microtubules and increase or inhibition of transmitter release at motor nerve terminal endings. Therefore, clinical studies of Hg toxicity in dentistry may provide new knowledge about disturbed metal homeostasis in neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis and mood disorders. The purpose of this MiniReview is to evaluate the evidence of possible relevance between Hg exposure in dentistry and idiopathic disturbances in motor functions, cognitive skills and affective reactions, as well as dose‐response relationships. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction, verbal and non-verbal communication, and stereotypic behaviors. Many studies support a significant relationship between many different environmental factors in ASD etiology. These factors include increased daily exposure to various toxic metal-based environmental pollutants, which represent a cause for concern in public health. This article reviews the most relevant toxic metals, commonly found, environmental pollutants, i.e., lead (Pb), mercury (Hg), aluminum (Al), and the metalloid arsenic (As). Additionally, it discusses how pollutants can be a possible pathogenetic cause of ASD through various mechanisms including neuroinflammation in different regions of the brain, fundamentally occurring through elevation of the proinflammatory profile of cytokines and aberrant expression of nuclear factor kappa B (NF-κB). Due to the worldwide increase in toxic environmental pollution, studies on the role of pollutants in neurodevelopmental disorders, including direct effects on the developing brain and the subjects’ genetic susceptibility and polymorphism, are of utmost importance to achieve the best therapeutic approach and preventive strategies. [ABSTRACT FROM AUTHOR]

Fibromyalgia (FM) is a complex chronic condition of unknown etiology, characterized by deep and widespread pain, sleep problems, cognitive impairment, fatigue, and other well-known functional symptoms. Recently, it has been proposed that an imbalance of nutritive components, including essential metal ions and vitamins, might play a critical role in the development of FM. Muscle pain has been associated with deficiencies in amino acids, magnesium, selenium, vitamins B and D, as well as with the harmful effects of heavy metals, such as mercury, cadmium, and lead. Research indicates that patients deficient in certain essential nutrients may develop dysfunction of pain inhibitory mechanisms together with fatigue and other FM symptoms. Additionally, mercury and other toxic elements may interfere with the bioavailability of essential nutrients. This review examines the many effects of metals and vitamins in pain evaluation of FM patients. Dietary guidance is therefore critical for FM patients to help them in correcting a suboptimal or deficient intake of essential nutrients. When optimal levels of nutrition are achieved, pain levels are usually lowered. Additional research is recommended in the field of FM and nutrition to disclose further possible relationships. [ABSTRACT FROM AUTHOR]

Mercury (Hg) is an environmental toxicant being present in the environment as elemental Hg (Hg 0 ), inorganic and organic Hg compounds. The nervous system is supposed to be the key target for Hg toxicity. Research indicates that selenium (Se) may be used as a protective agent against Hg neurotoxicity. Therefore, the aim of this review is to examine new implications of the molecular biology of Hg neurotoxicity, and specifically to focus on the influence of Se compounds and interfering thiols on Hg neurotoxicity at the molecular level. Mercury and Se form stable coordination compounds, and Hg species are characterized by higher affinity to selenol groups as compared to thiol groups. Therefore, Se-containing molecules are targets for Hg binding that may at least partially mediate the biological outcome of Hg-Se interaction. Molecular interaction between these elements also involves mutual interaction between Hg and various selenoproteins. Experimental data demonstrate that Se treatment modifies brain Hg retention, modulates neurotoxicity and oxidative stress in the nervous tissue of animals. Human data also indicate that molecular interaction between Hg and Se may have a significant influence on neurodevelopment, brain functioning, and neurodegeneration. It is hypothesized that the effectiveness of Se protection against Hg neurotoxicity may be determined by the dose of elements as well as their particular chemical forms. Further studies are required to estimate the intimate mechanisms of Hg and Se interaction in vivo . [ABSTRACT FROM AUTHOR]

The objective of the study was to investigate hair trace elements content in children suffering from autism spectrum disorder (ASD). A total of 74 ASD children and 74 sex- and age-matched controls divided into two age groups (2-4 and 5-9 years) were investigated. Hair trace elements content was assessed using inductively coupled plasma mass spectrometry. A general cohort of ASD children was characterized by 29 %, 41 %, and 24 % lower hair levels of chromium (Cr), iodine (I), and vanadium (V), respectively, whereas the level of selenium (Se) exceeded the respective control values by 31 %. In ASD children aged 2-4 years hair Cr, I and V content was 68 %, 36 % and 41 % lower than in the controls. Older ASD children were characterized by 45 % increase in hair Se levels. In a general cohort of ASD children hair beryllium (Be) and tin (Sn) levels were 50 % and 34 % lower than the control values. In the first age group (2-4 years) of ASD children 34 %, 42 %, and 73 % lower levels of arsenic (As), boron (B), and Be were detected. In the second age group of ASD children only a nearly significant 25 % decrease in hair lead (Pb) was detected. Surprisingly, no significant group difference in hair mercury (Hg), zinc (Zn), and copper (Cu) content was detected. Generally, the results of the present study demonstrate that children with ASD are characterized by lower values in hair of not only essential but also toxic trace elements. [ABSTRACT FROM AUTHOR]

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

Graphical abstract Highlights • Children with ASD, ASD and catatonia, and neurotypical controls were examined. • Hair and serum levels of trace elements and minerals were studied using ICP-MS. • The studied elements were different between ASD + catatonia, ASD, and controls. • Hair Hg, serum Al and Cd levels were negatively associated with catatonia in ASD. Abstract The objective of the study was to investigate the association between catatonia in autism spectrum disorder (ASD) and the levels of hair and serum trace elements and minerals in children with ASD. The levels of hair and serum trace elements and minerals of boys suffering from ASD with (n = 30) and without (n = 30) catatonia, as well as 30 age- and sex-matched neurotypical controls were assessed using ICP-MS. Hair calcium (Ca) and selenium (Se) levels were lower in ASD patients as compared to the controls. Hair mercury (Hg) levels in ASD patients were more than 3-fold and 2-fold higher as compared to the controls and children with catatonia in ASD. Hair iodine (I) and manganese (Mn) were the lowest and the highest in ASD + Catatonia, respectively. Serum aluminium (Al) and cadmium (Cd) levels in healthy controls were significantly higher in comparison to the patients of both groups. Serum chromium (Cr), copper (Cu) levels were significantly increased in patients with ASD and catatonia, whereas vanadium (V) levels were elevated in patients both with and without catatonia. Multiple regression analysis demonstrated that hair Hg and serum Al and Cd levels were negatively associated with catatonia in ASD in crude and adjusted models. Although the etiology of catatonia in ASD is unclear, the obtained data demonstrate that catatonic symptoms in ASD may be at least partially mediated by altered trace element levels. Further studies are required to elucidate the role of trace elements in the potential signaling mechanisms of catatonia. [ABSTRACT FROM AUTHOR]

• Interaction of Hg with biomolecules is mediated through its affinity to Cys thiol. • Cys and GSH Hg-conjugates play a significant role in Hg transport in vivo. • Hg-SH affinity interferes with Akt/CREB, Keap1/Nrf2, NF-κB-mediated apoptotic pathways. • Hg binding to Mn-SOD (Cys 196) and TrxR (Cys 497) may underlie its prooxidant effects. • Hg binding limits GSH and Trx (Cys 32 , 35 , 62 , 65 , 73) availability for redox reactions. The present study addresses existing data on the affinity and conjugation of sulfhydryl (thiol; -SH) groups of low- and high-molecular-weight biological ligands with mercury (Hg). The consequences of these interactions with special emphasis on pathways of Hg toxicity are highlighted. Cysteine (Cys) is considered the primary target of Hg, and link its sensitivity with thiol groups and cellular damage. In vivo , Hg complexes play a key role in Hg metabolism. Due to the increased affinity of Hg to SH groups in Cys residues, glutathione (GSH) is reactive. The geometry of Hg(II) glutathionates is less understood than that with Cys. Both Cys and GSH Hg-conjugates are important in Hg transport. The binding of Hg to Cys mediates multiple toxic effects of Hg, especially inhibitory effects on enzymes and other proteins that contain free Cys residues. In blood plasma, albumin is the main Hg-binding (Hg2+, CH 3 Hg+, C 2 H 5 Hg+, C 6 H 5 Hg+) protein. At the Cys 34 residue, Hg2+ binds to albumin, whereas other metals likely are bound at the N-terminal site and multi-metal binding sites. In addition to albumin, Hg binds to multiple Cys-containing enzymes (including manganese-superoxide dismutase (Mn-SOD), arginase I, sorbitol dehydrogenase, and δ-aminolevulinate dehydratase, etc.) involved in multiple processes. The affinity of Hg for thiol groups may also underlie the pathways of Hg toxicity. In particular, Hg-SH may contribute to apoptosis modulation by interfering with Akt/CREB, Keap1/Nrf2, NF-κB, and mitochondrial pathways. Mercury-induced oxidative stress may ensue from Cys-Hg binding and inhibition of Mn-SOD (Cys 196), thioredoxin reductase (TrxR) (Cys 497) activity, as well as limiting GSH (GS-HgCH 3) and Trx (Cys 32 , 35 , 62 , 65 , 73) availability. Moreover, Hg-thiol interaction also is crucial in the neurotoxicity of Hg by modulating the cytoskeleton and neuronal receptors, to name a few. However, existing data on the role of Hg-SH binding in the Hg toxicity remains poorly defined. Therefore, more research is needed to understand better the role of Hg-thiol binding in the molecular pathways of Hg toxicology and the critical role of thiols to counteract negative effects of Hg overload. [ABSTRACT FROM AUTHOR]