Ebselen protects glutamate uptake inhibition caused by methyl mercury but does not by Hg2+

Toxicology. 2005 Oct 15;214(1-2):57-66. doi: 10.1016/j.tox.2005.05.022.

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 (Hg2+) (50 microM) inhibited the glutamate net uptake from the cerebral cortex of 17-day-old rats; (ii) ebselen (10 microM) reverted the MeHg-induced inhibition of glutamate net uptake but did not protect the inhibition caused by Hg2+. 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 Hg2+; (iii) in addition, we observed that exposure of slices to 50 microM MeHg and Hg2+ 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 Hg2+ on cell viability. Conversely, ebselen did not modify the reduction of MTT caused by MeHg and Hg2+; (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azoles / pharmacology*
  • Benzene Derivatives / pharmacology
  • Cell Survival / drug effects
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / growth & development
  • Cerebral Cortex / metabolism
  • Glutamic Acid / metabolism*
  • In Vitro Techniques
  • Isoindoles
  • Mercuric Chloride / toxicity*
  • Methylmercury Compounds / toxicity*
  • Neuroprotective Agents / pharmacology*
  • Organoselenium Compounds / pharmacology*
  • Rats
  • Rats, Wistar

Substances

  • Azoles
  • Benzene Derivatives
  • Isoindoles
  • Methylmercury Compounds
  • Neuroprotective Agents
  • Organoselenium Compounds
  • diphenyldiselenide
  • Glutamic Acid
  • ebselen
  • Mercuric Chloride