title: N-acetyl-L-cysteine protects against cadmium-induced neuronal apoptosis by inhibiting ROS-dependent activation of Akt/mTOR pathway in mouse brain.
abstract: OBJECTIVE
  This study explores the neuroprotective effects and mechanisms of N-acetyl-L-cysteine (NAC) in mice exposed to cadmium (Cd).
  
  
  METHODS
  NAC (150 mg/kg) was intraperitoneally administered to mice exposed to Cd (10-50 mg/L) in drinking water for 6 weeks. The changes of cell damage and death, reactive oxygen species (ROS), antioxidant enzymes, as well as Akt/mammalian target of rapamycin (mTOR) signalling pathway in brain neurones were assessed. To verify the role of mTOR activation in Cd-induced neurotoxicity, mice also received a subacute regimen of intraperitoneally administered Cd (1 mg/kg) with/without rapamycin (7.5 mg/kg) for 11 days.
  
  
  RESULTS
  Chronic exposure of mice to Cd induced brain damage or neuronal cell death, due to ROS induction. Co-administration of NAC significantly reduced Cd levels in the plasma and brain of the animals. NAC prevented Cd-induced ROS and significantly attenuated Cd-induced brain damage or neuronal cell death. The protective effect of NAC was mediated, at least partially, by elevating the activities of Cu/Zn-superoxide dismutase, catalase and glutathione peroxidase, as well as the level of glutathione in the brain. Furthermore, Cd-induced activation of Akt/mTOR pathway in the brain was also inhibited by NAC. Rapamycin in vitro and in vivo protected against Cd-induced neurotoxicity.
  
  
  CONCLUSIONS
  NAC protects against Cd-induced neuronal apoptosis in mouse brain partially by inhibiting ROS-dependent activation of Akt/mTOR pathway. The findings highlight that NAC may be exploited for prevention and treatment of Cd-induced neurodegenerative diseases.
authors.affiliation: Jiangsu Key Laboratory for Microbes and Functional Genomics, Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Ren
authors.forename: Jinfei
authors.initials: J
authors.lastname: Zhang
authors.forename: Yangjing
authors.initials: Y
authors.lastname: Ye
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yijiao
authors.initials: Y
authors.lastname: Xu
authors.forename: Min
authors.initials: M
authors.lastname: Guo
authors.forename: Haiyan
authors.initials: H
authors.lastname: Ji
authors.forename: Chong
authors.initials: C
authors.lastname: Xu
authors.forename: Chenjian
authors.initials: C
authors.lastname: Gu
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.forename: Shile
authors.initials: S
authors.lastname: Huang
authors.forename: Long
authors.initials: L
authors.lastname: Chen
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002104:Cadmium / Q000097:blood / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D002104:Cadmium; C546843:mTOR protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D000111:Acetylcysteine
keywords: N-acetyl-L-cysteine; cadmium; mammalian target of rapamycin; neuronal apoptosis; reactive oxygen species