The pathology of methylmercury poisoning (Minamata disease)

Eto, Komyo; Marumoto, Masumi; Takeya, Motohiro

doi:10.1111/j.1440-1789.2010.01119.x

Cited by 85 publications

(44 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It can be postulated that, upon permeation of barriers, the final common pathway underlying the mechanism of intracellular CH3Hg+ toxicity is genotoxicity (Grotto et al 2009) due to its covalent binding of DNA (Maki and Ott 1981) and disruption of transcription pathways, leading to cellular instability and cell death. Exposure to significant doses of CH3Hg+ during pregnancy have resulted in offspring with significant neurodevelopmental abnormalities as was the case at Minamata Bay (Eto et al 2010). …”

Section: Discussionmentioning

confidence: 98%

Permeation thresholds for hydrophilic small biomolecules across microvascular and epithelial barriers are predictable on basis of conserved biophysical properties

Sarin¹

2015

In Silico Pharmacol.

View full text Add to dashboard Cite

PurposeNeutral small hydrophiles are permeable to varying degrees, across the aqueous pores of phospholipid bilayer protein channels, with their potential for permeation into cells being predictable, on the basis of hydrophilicity and size. Here, it is hypothesized that permeation thresholds for small hydrophiles, across capillary zona occludens tight junction and inter-epithelial junction pore complexes are predictable, on the basis of predicted hydrophilicity in context of predicted molecular size and charge distribution, as are those of cations and anions, on the basis of predicted ionization in context of predicted atomic size.MethodsSmall hydrophiles are categorized by charge distribution. 2-dimensional plots of predicted hydrophilic octanol-to-water partition coefficient (HOWPC; unitless) and predicted van der Waals diameter (vdWD; nm) are generated for each category. The predicted HOWPC-to-vdWD ratio (nm-1), and vdWDs for permeable hydrophile at the maximum and minimum HOWPC-to-vdWD, vdWD @ MAXimum HOWPC-to-vdWD and vdWD @ MINimum HOWPC-to-vdWD are determined. For cations and anions, the ionization-to-atomic diameter ratios (CI or AI-to-AD ratios; nm-1) are determined.ResultsPer sizes of mixed and pure polyneutral hydrophiles, the permeation size maximum for hydrophiles across tight junction pore complexes is >0.69 ≤ 0.73 nanometers and across inter-epithelial junction pore complexes is ≥ 0.81 nanometers. For hydrophiles with anionicity or cationicity, the vdWDs @ MAXimum HOWPC-to-vdWD are less than those of mixed and polyneutral hydrophiles across both tight and inter-epithelial junctions, ranges specific to category and junction type. For cations, the permeation threshold across tight junctions is between the CI-to-AD ratio of Na+ (+2.69 nm-1) and CH3-Hg+ (+2.36 nm-1), with CH3-Hg+ and K+ (+2.20 nm-1) being permeable; and for divalent cations, the threshold across inter-epithelial junctions is between the CI-to-AD ratio of Mg2+ (+6.25 nm-1) and Ca2+ (+5.08 nm-1) , Ca2+ being semi-permeable. For anions, the permeation threshold across tight junctions is between the AI-to-AD ratio of Cl- (-4.91 nm-1) and Br- (-4.17 nm-1), and the threshold across inter-epithelial junctions is between the AI-to-AD ratio of F- (-7.81 nm-1) and Cl- (-4.91 nm-1).ConclusionsIn silico modeling reveals that permeation thresholds, of small molecule hydrophiles, cations and anions across junctional pore complexes, are conserved in the physiologic state.Electronic supplementary materialThe online version of this article (doi:10.1186/s40203-015-0009-y) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 98%

Permeation thresholds for hydrophilic small biomolecules across microvascular and epithelial barriers are predictable on basis of conserved biophysical properties

Sarin¹

2015

In Silico Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Mercury has long been known to be toxic to humans, but it was the outbreak of the so-called Minamata disease, in which fi shermen and their families were exposed to high levels of methylmercury, that showed the tragic effects of marine mercury pollution (Eto et al 2010). Methylmercury is highly toxic, especially to the nervous system (Eto et al 2010), and may cause neurological damage at population level if the intake is high (Grandjean et al 1995).…”

Section: Mercurymentioning

confidence: 99%

“…Methylmercury is highly toxic, especially to the nervous system (Eto et al 2010), and may cause neurological damage at population level if the intake is high (Grandjean et al 1995). The chemical form of methylmercury in fi sh has been identifi ed as methylmercurycysteine (CH 3 Hgcyst), and probably occurs as part of proteins (Harris et al 2003).…”

Section: Mercurymentioning

confidence: 99%

Contamination of finfish with persistent organic pollutants and metals

Berntssen¹,

Maage²,

Lundebye³

2012

Chemical Contaminants and Residues in Food

View full text Add to dashboard Cite

“…All these effects correlate with the loss of neurons from several areas of the brain, among them the CGC layer (Korogi et al 1998 ;Ekino et al 2007 ;Eto et al 2010 ) . In addition to cerebellar neurodegeneration, abnormal migration of neurons in the cerebellum and microtubule formation defi cits were observed during fetal neural development and in affected newborn babies (Choi et al 1978 ;Castoldi et al 2000 ) .…”

Section: Introductionmentioning

confidence: 98%

“…Based on two epidemics of MeHg poisoning (Minamata Bay, Japan and Iraq) and on recent prospective studies on general population, ingestion of contaminated food can be considered as the primary route of exposure (Grandjean 2007 ;Ramón et al 2008 ) . Observational studies of individuals exposed early in life in Minamata, where inorganic mercury was discharged in waste water from a chemical plant and biotransformed to MeHg by sea organisms and biomagnifi ed through the trophic chain, have shown that both developmental and aging states exacerbated the neurotoxic effects of this organometal, with primary signs of neurological dysfunction such as cerebellar ataxia, visual impairment, weakness of extremities, and sensory disturbances (Eto et al 2010 ;Ekino et al 2007 ;Murata et al 2007 ) . Psychiatric effects have also been related to MeHg exposures in Minamata (Yorifuji et al 2011 ) .…”

Section: Introductionmentioning

confidence: 99%

In Vitro Models for Methylmercury Neurotoxicity: Effects on Glutamatergic Cerebellar Granule Neurons

Suñol

Rodrı́guez-Farré

2012

Methylmercury and Neurotoxicity

View full text Add to dashboard Cite

Methylmercury (MeHg), a relevant persistent environmental contaminant, is widely recognized as a potent neurotoxicant in humans. The clinical features of MeHg-intoxicated people are characterized by neurological dysfunction that induces cerebellar-based ataxia, generalized extremity weakness, and sensory disturbances including speech, vision, and hearing impairment, which correlate with the loss of neurons from several areas of the brain, among them the cerebellar granule cell (CGC) layer. CGCs are glutamatergic neurons that are successfully grown in vitro. Here, we report the effects of short and long term exposure to MeHg on primary cultures of CGCs. Short exposure to micromolar concentrations of MeHg inhibits neuronal glutamate uptake and induces the release of endogenous glutamate, the increase of intracellular calcium and of oxidative stress. After continuous exposure to low MeHg concentration (in the nanomolar range) oxidative stress results in lipid peroxidation and cell death which are reduced by the glutathione peroxidase (GPx)-enhancing antioxidant probucol or by overexpressing GPx in the cells. Decreased phosphorylation and translocation of cofi lin from the cytosol to the mitochondria are also early hallmarks of MeHg-induced toxicity in cultured cerebellar granule neurons.

show abstract

The pathology of methylmercury poisoning (Minamata disease)

Cited by 85 publications

References 9 publications

Permeation thresholds for hydrophilic small biomolecules across microvascular and epithelial barriers are predictable on basis of conserved biophysical properties

Permeation thresholds for hydrophilic small biomolecules across microvascular and epithelial barriers are predictable on basis of conserved biophysical properties

Contamination of finfish with persistent organic pollutants and metals

In Vitro Models for Methylmercury Neurotoxicity: Effects on Glutamatergic Cerebellar Granule Neurons

Contact Info

Product

Resources

About