Acetyl-L-carnitine provides effective in vivo neuroprotection over 3,4-methylenedioximethamphetamine-induced mitochondrial neurotoxicity in the adolescent rat brain
| Autor: | Eduarda Fernandes, Teresa Summavielle, Eduardo Alves, Z. Binienda, Cecília J. Alves, Maria Amélia Tavares, M. de Lourdes Bastos, Félix Carvalho |
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| Rok vydání: | 2008 |
| Předmět: |
Serotonin
Mitochondrial Diseases Fever N-Methyl-3 4-methylenedioxyamphetamine Respiratory chain Mitochondrion Pharmacology Neuroprotection DNA Mitochondrial Protein Carbonylation mental disorders medicine Cytochrome c oxidase Animals Rats Wistar Inner mitochondrial membrane biology Chemistry General Neuroscience Body Weight Neurotoxicity Brain Membrane Proteins MDMA NADH Dehydrogenase Hydroxyindoleacetic Acid medicine.disease Mitochondria Rats Biochemistry Vitamin B Complex biology.protein Cyclooxygenase 1 Hallucinogens Monoamine oxidase B Lipid Peroxidation Acetylcarnitine psychological phenomena and processes medicine.drug |
| Zdroj: | Neuroscience. 158(2) |
| ISSN: | 0306-4522 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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