L-carnitine and neuroprotection in the animal model of mitochondrial dysfunction.
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.
Binienda
Zbigniew
Z
Division of Neurotoxicology, HFT-132, National Center for Toxicology Research, Food and Drug Administration, Jefferson, Arkansas 72079-9502, USA. zbinienda@nctr.fda.gov
Przybyla-Zawislak
Beata
B
Virmani
Ashraf
A
Schmued
Larry
L
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002331:Carnitine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D017237:Mitochondrial Encephalomyopathies / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors
D018696:Neuroprotective Agents; D013385:Succinate Dehydrogenase; D002331:Carnitine