title: Protective effect of L-carnitine against H(2)O(2)-induced neurotoxicity in neuroblastoma (SH-SY5Y) cells.
abstract: OBJECTIVE
  4-N-trimethylammonium-3-hydroxybutyric acid (L-carnitine) is an endogenous mitochondrial membrane compound and some studies have reported that L-carnitine could effectively protect various cells against oxidative injury both in vitro and in vivo. In the present study, we used the human neuroblastoma SH-SY5Y cell line as an in vitro model and assessed the effect of L-carnitine on hydrogen peroxide (H(2)O(2))-mediated oxidative stress and neurotoxicity.
  
  
  METHODS
  Cells in culture were treated with different concentrations of H(2)O(2) alone or pretreated with L-carnitine. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, transmission electron microscopy, agarose gel electrophoresis, biochemical methods, and Western blotting were employed in the present study.
  
  
  RESULTS
  Pretreatment with L-carnitine for 3 hours inhibited H(2)O(2)-induced cell viability loss, morphological changes, intracellular reactive oxygen species generation, and lipid peroxidation in a concentration-dependent manner. Endogenous anti-oxidant defense components including total anti-oxidative capacity, glutathione peroxidase, catalase, and superoxide dismutase were also promoted by L-carnitine. Meanwhile, H(2)O(2)-induced down-regulation of Bcl-2, up-regulation of Bax, and DNA damage and apoptosis were also inhibited in the presence of L-carnitine.
  
  
  CONCLUSIONS
  Taken together, these results suggest that L-carnitine may function as an anti-oxidant to inhibit H(2)O(2)-induced oxidative stress as well as regulation of Bcl-2 family and prevent the apoptotic death of neuronal cells, which might be beneficial for the treatment of oxidative stress in neurodegenerative diseases.
authors.affiliation: Department of Pharmacology, Medical College, Qingdao University, Qingdao, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Junli
authors.initials: J
authors.lastname: Ye
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Liu
authors.forename: Yantao
authors.initials: Y
authors.lastname: Han
authors.forename: Chunbo
authors.initials: C
authors.lastname: Wang
mesh_terms: D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002331:Carnitine / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004347:Drug Interactions; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D006861:Hydrogen Peroxide; D002331:Carnitine