Neurotoxicity of organic and inorganic mercury species – Effects on and transfer across the blood-cerebrospinalfluid barrier, cytotoxic effects in target cells

Abstract

Mercury (Hg) is an environmental contaminant. Whereas within terrestrial food sources it is mostly found as inorganic Hg, in fish and seafood it is largely present in form of methylmercury. Because of its antibacterial/antifungal properties the organic Hg compound thiomersal is used as a preservative in medical preparations. However, exposure to organic Hg promotes primarily neurological effects. The tolerable weekly intake (TWI) of 1.6 mg/kg body weight for methylmercury has been recently reevaluated by the EFSA in 2012. Based on epidemiological studies a new TWI of 1.3 mg/kg body weight has been established EFSA Panel on Contaminants in the Food Chain, 2012. Up to date the transfer of Hg compounds into the brain and the mechanisms of Hg species induced neurotoxicity are not clearly understood. Here we apply an in vitro model of the blood-cerebrospinalfluid (CSF) barrier to identify the transfer mechanisms of different Hg species in the brain and to characterize their effects on the barrier properties. In first studies effects of mercury chloride (HgCl 2 ), methylmercury (MeHgCl) and thiomersal (THI) on the barrier integrity have been analyzed. Quantitative analysis of the total Hg amount in aliquots of both, blood and brain side of the in vitro barrier system, will give information about the Hg-species dependent transfer properties. The respective method to quantify Hg via ICP-MS/MS has already been established. Our studies indicate that the barrier system is significantly more sensitive towards organic Hg species as compared to inorganic compounds. These results are in agreement with our studies concerning the cytotoxicity of the Hg compounds in the barrier building porcine epithelial cells of the Plexus choroideus.In order to identify potential target cells of Hg mediated neurotoxicity, cytotoxic effects of the Hg species have been performed in different cell lines. Using the neutral red uptake assay based on the lysosomal integrity, differentiated human neurons (LUHMES) seem to be more sensitive towards organic and inorganic Hg species compared to human astrocytes. In both cell lines inorganic Hg shows a lower cytotoxicity compared to the organic species.

Neurotoxic Agents and Peripheral Neuropathy

“…The vapor form of Hg is more dangerous and can is readily absorbed from the lungs (80%) and distributed throughout the body [8]. A wide variety of fields in that Hg have been used, such as gold mining, fluorescent light bulbs production, ingredients of antiaging creams, fungicides to protect plants against infections, and protection in multidose vials of vaccines [34,35].…”