L-carnitine protects against nickel-induced neurotoxicity by maintaining mitochondrial function in Neuro-2a cells
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 (NiCl{sub 2}) (0.25, 0.5, 1, and 2 mM) for 24 h, or to 0.5 mM and 1 mM NiCl{sub 2} 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 ({Delta}{Psi}{sub 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.
- OSTI ID:
- 21535296
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 253, Issue 1; Other Information: DOI: 10.1016/j.taap.2011.03.008; PII: S0041-008X(11)00094-9; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ADENOSINE
ATP
CARNITINE
DNA
LACTATE DEHYDROGENASE
LYSINE
MEMBRANES
METHIONINE
MICE
MITOCHONDRIA
NERVOUS SYSTEM
NICKEL
NICKEL CHLORIDES
QUATERNARY AMMONIUM COMPOUNDS
RNA
TOXICITY
AMINO ACIDS
AMMONIUM COMPOUNDS
ANIMALS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHLORIDES
CHLORINE COMPOUNDS
DRUGS
ELEMENTS
ENZYMES
HALIDES
HALOGEN COMPOUNDS
HEMIACETAL DEHYDROGENASES
HYDROXY ACIDS
LIPOTROPIC FACTORS
MAMMALS
METALS
NICKEL COMPOUNDS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXIDOREDUCTASES
PROTEINS
RIBOSIDES
RODENTS
TRANSITION ELEMENT COMPOUNDS
TRANSITION ELEMENTS
VERTEBRATES
VITAMIN B GROUP
VITAMINS