Neurotoxicity of organomercurial compounds

Abstract

Mercury is a ubiquitous contaminant, and a range of chemical species is generated by human activity and natural environmental change. Elemental mercury and its inorganic and organic compounds have different toxic properties, but all them are considered hazardous in human exposure. In an equimolecular exposure basis, organomercurials with a short aliphatic chain are the most harmful compounds and they may cause irreversible damage to the nervous system. Methylmercury (CH(3)Hg(+)) is the most studied following the neurotoxic outbreaks identified as Minamata disease and the Iraq poisoning. The first description of the CNS pathology dates from 1954. Since then, the clinical neurology, the neuropathology and the mechanisms of neurotoxicity of organomercurials have been widely studied. The high thiol reactivity of CH(3)Hg(+), as well as all mercury compounds, has been suggested to be the basis of their harmful biological effects. However, there is clear selectivity of CH(3)Hg(+) for specific cell types and brain structures, which is not yet fully understood. The main mechanisms involved are inhibition of protein synthesis, microtubule disruption, increase of intracellular Ca(2+) with disturbance of neurotransmitter function, oxidative stress and triggering of excitotoxicity mechanisms. The effects are more damaging during CNS development, leading to alterations of the structure and functionality of the nervous system. The major source of CH(3)Hg(+) exposure is the consumption of fish and, therefore, its intake is practically unavoidable. The present concern is on the study of the effects of low level exposure to CH(3)Hg(+) on human neurodevelopment, with a view to establishing a safe daily intake. Recommendations are 0.4 micro g/kg body weight/day by the WHO and US FDA and, recently, 0.1 micro g/kg body weight/day by the US EPA. Unfortunately, these levels are easily attained with few meals of fish per week, depending on the source of the fish and its position in the food chain.

Localizing organomercury uptake and accumulation in zebrafish larvae at the tissue and cellular level

“…Ocular manifestations of organic Hg exposure were also observed in victims of mass poisoning outbreaks in Iraq (26) and Japan (27), and a recent case of a patient with failing visual acuity was attributed to the patient's high intake of predatory fish (28). Visual defects, such as partial or complete loss of vision and constriction in peripheral visual fields, are common results of organic Hg poisoning and are known to reflect neuronal loss in certain parts of the brain (29). Our data using methyl-or ethylmercury-exposed zebrafish larvae reveal that a large accumulation of Hg can occur in the eye and especially in the lens epithelium.…”

New melanic pigments in the human brain that accumulate in aging and block environmental toxic metals

“…This selective entry could explain the high susceptibility of cerebellum neurons to mercury toxicity. Indeed, mercury exposure induces motor deficits, targeting cerebellar cells (27,28). Neuromelanin in the substantia nigra also accumulates an extremely high amount of lead.…”

Thimerosal Neurotoxicity is Associated with Glutathione Depletion: Protection with Glutathione Precursors

“…Organic mercury has a high affinity for the thiol (-SH) group on glutathione, a tripeptide composed of cysteine, glutamate, and glycine (Sanfeliu et al, 2003). The cysteine moiety of glutathione carries the active thiol group that binds and detoxifies a variety of heavy metals, including organic and inorganic mercury.…”