l-Carnitine and Neuroprotection in the Animal Model of Mitochondrial Dysfunction

• Published in: Annals of the New York Academy of Sciences Vol. 1053; no. 1; pp. 174 - 182
• Main Authors: BINIENDA, ZBIGNIEW, PRZYBYLA-ZAWISLAK, BEATA, VIRMANI, ASHRAF, SCHMUED, LARRY
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2005
• Subjects: 3-nitropropionic acid; Animals; Body Temperature - drug effects; carnitine; Carnitine - pharmacology; Disease Models, Animal; Electroencephalography - drug effects; Male; mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial Encephalomyopathies - chemically induced; Mitochondrial Encephalomyopathies - metabolism; Mitochondrial Encephalomyopathies - prevention & control; Neurodegenerative Diseases - chemically induced; Neurodegenerative Diseases - pathology; Neurodegenerative Diseases - prevention & control; Neurons - pathology; neuroprotection; Neuroprotective Agents - pharmacology; Oxidative Stress - drug effects; Rats; Rats, Sprague-Dawley; striatum; Succinate Dehydrogenase - antagonists & inhibitors
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.2005.tb00023.x

: We have shown previously that pretreatment with l‐carnitine (LC) prior to 3‐nitropropionic acid (3‐NPA) exposure, while not significantly attenuating succinate dehydrogenase (SDH) inhibition, prevented hypothermia and oxidative stress. The plant and fungal toxin, 3‐NPA, acts as an inhibitor of mitochondrial function via irreversible inactivation of the mitochondrial inner membrane enzyme, SDH. Inhibition of SDH disturbs electron transport, leading to cellular energy deficits and oxidative stress‐related neuronal injury. In the study presented here, a neurohistological method was applied to examine the mitochondriotropic effect of LC pretreatment against 3‐NPA‐induced neurotoxicity. Twenty adult male Sprague‐Dawley rats randomly divided into two groups (n= 10/group) were injected twice with 3‐NPA at 30 mg/kg sc, at 2 days apart, or received LC pretreatment at 100 mg/kg, at 30‐40 min before 3‐NPA administration. Rats in both groups were perfused 7 days later and their brains harvested. Degenerating neurons were identified and localized via the fluorescent marker Fluoro‐Jade B. Data analysis showed that LC was protective against 3‐NPA‐induced toxicity, as reflected by both reduced mortality and significantly reduced neuronal degeneration.