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| Research article summary (published 28 Oct 2008): |
Acetyl-L-carnitine provides effective in vivo neuroprotection over 3,4-methylenedioximethamphetamine-induced mitochondrial neurotoxicity in the adolescent rat brain.
Full Abstract
3,4-Methylenedioximethamphetamine (MDMA, ecstasy) is a worldwide abused stimulant drug, with persistent neurotoxic effects and high prevalence among adolescents. The massive release of 5-HT from pre-synaptic storage vesicles induced by MDMA followed by monoamine oxidase B (MAO-B) metabolism, significantly increases oxidative stress at the mitochondrial level. l-Carnitine and its ester, acetyl-l-carnitine (ALC), facilitate the transport of long chain free fatty acids across the mitochondrial membrane enhancing neuronal anti-oxidative defense. Here, we show the potential of ALC against the neurotoxic effects of MDMA exposure. Adolescent male Wistar rats were assigned to four groups: control saline solution, isovolumetric to the MDMA solution, administered i.p.; MDMA (4x10 mg/kg MDMA, i.p.); ALC/MDMA (100 mg/kg 30 min of ALC prior to MDMA, i.p.) and ALC (100 mg/kg, i.p.). Rats were killed 2 weeks after exposure and brains were analyzed for lipid peroxidation, carbonyl formation, mitochondrial DNA (mtDNA) deletion and altered expression of the DNA-encoded subunits of the mitochondrial complexes I (NADH dehydrogenase, NDII) and IV (cytochrome c oxidase, COXI) from the respiratory chain. Levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) were also assessed. The present work is the first to successfully demonstrate that pretreatment with ALC exerts effective neuroprotection against the MDMA-induced neurotoxicity at the mitochondrial level, reducing carbonyl formation, decreasing mtDNA deletion, improving the expression of the respiratory chain components and preventing the decrease of 5-HT levels in several regions of the rat brain. These results indicate potential benefits of ALC application in the prevention and treatment of neurodegenerative disorders.
Author information
Author/s: Alves, E (E); Binienda, Z (Z); Carvalho, F (F); Alves, C J (CJ); Fernandes, E (E); de Lourdes Bastos, M (M); Tavares, M A (MA); Summavielle, T (T);
Affiliation: IBMC-Instituto de Biologia Molecular e Celular, Molecular Neurobiology, Neuroprotection Laboratory, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal.
Journal and publication information
Publication Type: Journal Article; Research Support, Non-U.S. Gov't
Journal: Neuroscience (Neuroscience), published in United States. (Language: eng)
Reference: 2009-Jan; vol 158 (issue 2) : pp 514-23
Dates: Created 2009/01/19; Completed 2009/04/15;
PMID: 19015003, status: MEDLINE (last retrieved date: 4/15/2009)
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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Associated Chemicals: DNA, Mitochondrial (0) ; Hallucinogens (0) ; Membrane Proteins (0) ; Vitamin B Complex (12001-76-2) ; Acetylcarnitine (14992-62-2) ; N-Methyl-3,4-methylenedioxyamphetamine (42542-10-9) ; Serotonin (50-67-9) ; Hydroxyindoleacetic Acid (54-16-0) ; Cyclooxygenase 1 (EC 1.14.99.1) ; Ptgs1 protein, rat (EC 1.14.99.1) ; NADH Dehydrogenase (EC 1.6.99.3)Related articles
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