Acetyl-l-carnitine provides effective in vivo neuroprotection over 3,4-methylenedioximethamphetamine-induced mitochondrial neurotoxicity in the adolescent rat brain
by
Alves E, Binienda Z, Carvalho F, Alves CJ, Fernandes E,
de Lourdes Bastos M, Tavares MA, Summavielle T.
IBMC-Instituto de Biologia Molecular e Celular,
Molecular Neurobiology, Neuroprotection Laboratory,
Rua do Campo Alegre, 823, 4150-180 Porto, Portugal;
REQUIMTE, Toxicology Department, Faculty of Pharmacy,
Universidade do Porto (UP), Porto, Portugal
zhuojun88@sina.com
Neuroscience. 2009 Jan 23;158(2):514-23.

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.

History
Acetylcholine
Controversies
Protect and survive

Refs
and further reading

HOME
HedWeb
Nootropics
cocaine.wiki
Future Opioids
BLTC Research
MDMA/Ecstasy
Superhapiness?
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

Refs
and further reading

HOME
HedWeb
Nootropics
cocaine.wiki
Future Opioids
BLTC Research
MDMA/Ecstasy
Superhapiness?
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family