Accumulation of methylmercury and inorganic mercury in the brain

Friberg, L; Mottet, N. Karle

doi:10.1007/bf02917253

Cited by 108 publications

(46 citation statements)

References 9 publications

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“…However, demethylation rates for MeHg are relatively slow (Norseth and Clarkson, 1970;Friberg and Mottet, 1989). In rats, demethylation rates are estimated to be about 3 to 5% per day (Norseth and Clarkson, 1970) and, thus, should not influence the present short-term studies.…”

Section: Mrp2-mediated Mehg-n-acetylcysteine Transport 381mentioning

confidence: 85%

Accelerated Urinary Excretion of Methylmercury following Administration of Its AntidoteN-Acetylcysteine Requires Mrp2/Abcc2, the Apical Multidrug Resistance-Associated Protein

Madejczyk¹,

Aremu²,

Simmons-Willis³

et al. 2007

J Pharmacol Exp Ther

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N-Acetylcysteine (NAC) is a sulfhydryl-containing compound that produces a dramatic acceleration of urinary methylmercury (MeHg) excretion in poisoned mice, but the molecular mechanism for this effect is poorly defined. MeHg readily binds to NAC to form the MeHg-NAC complex, and recent studies indicate that this complex is an excellent substrate for the basolateral organic anion transporter (Oat)-1, Oat1/Slc22a6, thus potentially explaining the uptake from blood into the renal tubular cells. The present study tested the hypothesis that intracellular MeHg is subsequently transported across the apical membrane of the cells into the tubular fluid as a MeHg-NAC complex using the multidrug resistance-associated protein-2 (Mrp2/Abcc2). NAC markedly stimulated urinary [14 C]MeHg excretion in wild-type Wistar rats, and a second dose of NAC was as effective as the first dose in stimulating MeHg excretion. In contrast with the normal Wistar rats, NAC was much less effective at stimulating urinary MeHg excretion in the Mrp2-deficient (TRϪ) Wistar rats. The TRϪ rats excreted only ϳ30% of the MeHg excreted by the wild-type animals. To directly test whether MeHg-NAC is a substrate for Mrp2, studies were carried out in plasma membrane vesicles isolated from livers of TRϪ and control Wistar rats. Transport of MeHg-NAC was lower in vesicles prepared from TRϪ rats, whereas transport of MeHg-cysteine was similar in control and TRϪ rats. These results indicate that Mrp2 is involved in urinary MeHg excretion after NAC administration and suggest that the transported molecule is most likely the MeHg-NAC complex.

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Section: Mrp2-mediated Mehg-n-acetylcysteine Transport 381mentioning

confidence: 85%

Accelerated Urinary Excretion of Methylmercury following Administration of Its AntidoteN-Acetylcysteine Requires Mrp2/Abcc2, the Apical Multidrug Resistance-Associated Protein

Madejczyk¹,

Aremu²,

Simmons-Willis³

et al. 2007

J Pharmacol Exp Ther

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“…Previous work reported, after exposure to metallic Hg vapour, the presence of inorganic Hg in brain, probably due to its bond with selenium (Friberg and Mottet 1989). Recent evidence suggests a disruption in Na/K ATPase activity in the cerebral vessels and a Ca 2+ -mimetic action of the metal as the two possible pathways for inorganic Hg absorption by the CNS (Choi et al 2011).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 98%

Ameliorative effects of egg white hydrolysate on recognition memory impairments associated with chronic exposure to low mercury concentration

Rizzetti

Altermann

Martinez

et al. 2016

Neurochemistry International

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The study aimed to investigate whether the Egg White Hydrolysate (EWH) is able to prevent the recognition memory disorders associated with long-term Hg exposure in by atomic fluorescence spectrometry. We confirm that the STM and LTM were impaired in adult rats exposed to Hg at low concentrations, which may be related to the increased metal deposition, ROS production and subsequent oxidative damage in the hippocampus. In addition, we demonstrated for the first time that EWH treatment is able to prevent memory impairment induced by Hg exposure, reducing Hg content and ROS production in the hippocampus. In conclusion, EWH prevents memory impairments induced by chronic exposure to low doses of Hg. These findings may represent a good public health strategy since they indicate that EWH is a promising candidate as a new natural therapy for heavy metal intoxication.

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“…IM binding to selenium is almost irreversible and contributes to its longterm brain retention [23,24]. Mercury from gaseous sources, such as coal burning, and from human activities through waste water, is accumulated in the food chain, and comes back to humans mainly via fish as methyl-mercury.…”

Section: Introductionmentioning

confidence: 99%

Does Inorganic Mercury Play a Role in Alzheimer's Disease? A Systematic Review and an Integrated Molecular Mechanism

Mutter¹,

Curth

Naumann³

et al. 2010

JAD

147

113

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Abstract. Mercury is one of the most toxic substances known to humans. It has been introduced into the human environment and has also been widely used in medicine. Since circumstantial evidence exists that the pathology of Alzheimer's disease (AD) might be in part caused or exacerbated by inorganic mercury, we conducted a systematic review using a comprehensive search strategy. Studies were screened according to a pre-defined protocol. Two reviewers extracted relevant data independent of each other. One thousand and forty one references were scrutinized, and 106 studies fulfilled the inclusion criteria. Most studies were case control or comparative cohort studies. Thirty-two studies, out of 40 testing memory in individuals exposed to inorganic mercury, found significant memory deficits. Some autopsy studies found increased mercury levels in brain tissues of AD patients. Measurements of mercury levels in blood, urine, hair, nails, and cerebrospinal fluid were inconsistent. In vitro models showed that inorganic mercury reproduces all pathological changes seen in AD, and in animal models inorganic mercury produced changes that are similar to those seen in AD. Its high affinity for selenium and selenoproteins suggests that inorganic mercury may promote neurodegenerative disorders via disruption of redox regulation. Inorganic mercury may play a role as a co-factor in the development of AD. It may also increase the pathological influence of other metals. Our mechanistic model describes potential causal pathways. As the single most effective public health primary preventive measure, industrial, and medical usage of mercury should be eliminated as soon as possible.

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Accumulation of methylmercury and inorganic mercury in the brain

Cited by 108 publications

References 9 publications

Accelerated Urinary Excretion of Methylmercury following Administration of Its AntidoteN-Acetylcysteine Requires Mrp2/Abcc2, the Apical Multidrug Resistance-Associated Protein

Accelerated Urinary Excretion of Methylmercury following Administration of Its AntidoteN-Acetylcysteine Requires Mrp2/Abcc2, the Apical Multidrug Resistance-Associated Protein

Ameliorative effects of egg white hydrolysate on recognition memory impairments associated with chronic exposure to low mercury concentration

Does Inorganic Mercury Play a Role in Alzheimer's Disease? A Systematic Review and an Integrated Molecular Mechanism

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