title: Riluzole-triggered GSH synthesis via activation of glutamate transporters to antagonize methylmercury-induced oxidative stress in rat cerebral cortex.
abstract: OBJECTIVE
  This study was to evaluate the effect of riluzole on methylmercury- (MeHg-) induced oxidative stress, through promotion of glutathione (GSH) synthesis by activating of glutamate transporters (GluTs) in rat cerebral cortex.
  
  
  METHODS
  Eighty rats were randomly assigned to four groups, control group, riluzole alone group, MeHg alone group, and riluzole + MeHg group. The neurotoxicity of MeHg was observed by measuring mercury (Hg) absorption, pathological changes, and cell apoptosis of cortex. Oxidative stress was evaluated via determining reactive oxygen species (ROS), 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDAs), carbonyl, sulfydryl, and GSH in cortex. Glutamate (Glu) transport was studied by measuring Glu, glutamine (Gln), mRNA, and protein of glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1).
  
  
  RESULTS
  (1) MeHg induced Hg accumulation, pathological injury, and apoptosis of cortex; (2) MeHg increased ROS, 8-OHdG, MDA, and carbonyl, and inhibited sulfydryl and GSH; (3) MeHg elevated Glu, decreased Gln, and downregulated GLAST and GLT-1 mRNA expression and protein levels; (4) riluzole antagonized MeHg-induced downregulation of GLAST and GLT-1 function and expression, GSH depletion, oxidative stress, pathological injury, and apoptosis obviously.
  
  
  CONCLUSIONS
  Data indicate that MeHg administration induced oxidative stress in cortex and that riluzole could antagonize this situation through elevation of GSH synthesis by activating of GluTs.
authors.affiliation: Department of Enviromental Health, School of Public Health, China Medical University, Liaoning, Shenyang 110001, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Deng
authors.forename: Zhao-Fa
authors.initials: ZF
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Yang
authors.forename: Yan-Gang
authors.initials: YG
authors.lastname: Wei
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D015536:Down-Regulation; D027342:Excitatory Amino Acid Transporter 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008767:Methylmercury Compounds / Q000633:toxicity*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D019782:Riluzole / Q000494:pharmacology*
chemical_list: D027322:Amino Acid Transport System X-AG; D027342:Excitatory Amino Acid Transporter 2; D008767:Methylmercury Compounds; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D005973:Glutamine; D018698:Glutamic Acid; D008315:Malondialdehyde; D019782:Riluzole; D000080242:8-Hydroxy-2'-Deoxyguanosine; C073972:dimethyl mercury; D003849:Deoxyguanosine; D005978:Glutathione