title: L-carnitine protects against nickel-induced neurotoxicity by maintaining mitochondrial function in Neuro-2a cells.
abstract: Mitochondrial dysfunction is thought to be a part of the mechanism underlying nickel-induced neurotoxicity. L-carnitine (LC), a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine in all mammalian species, manifests its neuroprotective effects by improving mitochondrial energetics and function. The purpose of this study was to investigate whether LC could efficiently protect against nickel-induced neurotoxicity. Here, we exposed a mouse neuroblastoma cell line (Neuro-2a) to different concentrations of nickel chloride (NiCl₂) (0.25, 0.5, 1, and 2 mM) for 24 h, or to 0.5 mM and 1 mM NiCl₂ for various periods (0, 3, 6, 12, or 24 h). We found that nickel significantly increased the cell viability loss and lactate dehydrogenase (LDH) release in Neuro-2a cells. In addition, nickel exposure significantly elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels, disrupted the mitochondrial membrane potential (ΔΨ(m)), reduced adenosine-5'-triphosphate (ATP) concentrations and decreased mitochondrial DNA (mtDNA) copy numbers and mtRNA transcript levels. However, all of the cytotoxicities and mitochondrial dysfunctions that were triggered by nickel were efficiently attenuated by pretreatment with LC. These protective effects of LC may be attributable to its role in maintaining mitochondrial function in nickel-treated cells. Our results suggest that LC may have great pharmacological potential in protecting against the adverse effects of nickel in the nervous system.
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, People's Republic of China.
authors.forename: Min-Di
authors.initials: MD
authors.lastname: He
authors.forename: Shang-Cheng
authors.initials: SC
authors.lastname: Xu
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Lu
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Zhong
authors.forename: Yan-Wen
authors.initials: YW
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Ju
authors.initials: J
authors.lastname: Yang
authors.forename: Guang-Bin
authors.initials: GB
authors.lastname: Zhang
authors.forename: Zheng-Ping
authors.initials: ZP
authors.lastname: Yu
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002331:Carnitine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology*; D020258:Neurotoxicity Syndromes / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D009532:Nickel / Q000037:antagonists & inhibitors / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; C022838:nickel chloride; D009532:Nickel; D002331:Carnitine