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 (CH3Hg+) 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 CH3Hg+, as well as all mercury compounds, has been suggested to be the basis of their harmful biological effects. However, there is clear selectivity of CH3Hg+ 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 Ca2+ 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 CH3Hg+ 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 CH3Hg+ on human neurodevelopment, with a view to establishing a safe daily intake. Recommendations are 0.4 µg/kg body weight/day by the WHO and US FDA and, recently, 0.1 µg/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.