Ebselen protects glutamate uptake inhibition caused by methyl mercury but does not by Hg 2+

Abstract

Alterations of the neurotransmitter release systems in CNS have been reported in a variety of neuropathological processes associated with heavy metal toxicity. Neurotoxic effects of mercurials were investigated in vitro in cerebral cortex slices from young rats. The present study indicates that: (i) the environmental contaminants methylmercury (MeHg) and mercuric chloride (Hg 2+) (50 μM) inhibited the glutamate net uptake from the cerebral cortex of 17-day-old rats; (ii) ebselen (10 μM) reverted the MeHg-induced inhibition of glutamate net uptake but did not protect the inhibition caused by Hg 2+. At same time, we investigated another diorganochalcogenide, diphenyl diselenide (PhSe) 2 and it was observed that this compound did not revert the action of MeHg or Hg 2+; (iii) in addition, we observed that exposure of slices to 50 μM MeHg and Hg 2+ for 30 min followed by Trypan blue exclusion assay resulted in 58.5 and 67.5% of staining cells, respectively, indicating a decrease in cell viability. Ebselen protected slices from the deleterious effects of MeHg, but not of Hg 2+ on cell viability. Conversely, ebselen did not modify the reduction of MTT caused by MeHg and Hg 2+; (iv) the protective effect of ebselen on MeHg-induced inhibition of glutamate net uptake seems to be related to its ability in maintaining cell viability.