Neuroprotective role of L-carnitine in the 3-nitropropionic acid induced neurotoxicity.
L-carnitine (LC) plays an important regulatory role in the mitochondrial transport of long-chain free fatty acids (FFA). 3-Nitropropionic acid (3-NPA) is known to induce cellular energy deficit and oxidative stress related neurotoxicity via an irreversible inhibition of the mitochondrial enzyme succinate dehydrogenase (SDH). Protective effects of L-carnitine on the neurotoxicity induced by 3-NPA have been shown in vitro. Here, the activities of SDH as well as the activity of the antioxidant enzymes, catalase (CAT), and superoxide dismutase (SOD) were measured in order to evaluate the protective action of LC against 3-NPA-induced neurotoxicity. Male, CD Sprague-Dawley rats, 3-month old, were injected with either 50 or 100 mg/kg of LC, i.p., 30-60 min prior to 3-NPA (30 mg/kg, s.c.) or with 3-NPA alone. Enzyme activities were assayed in caudate nucleus (CN), frontal cortex (FC), and hippocampus (HIP) post sacrifice. Increased activities of CAT and SOD were observed after treatment with 3-NPA alone. Pretreatment with low or high doses of LC was associated with attenuation of these increases equivalent to, or below, the control levels. In rats treated with 3-NPA alone, SDH activity was inhibited by 62% (CN), 50% (FC), and 65% (HIP) of controls. Pretreatment with LC prior to 3-NPA attenuated decreases of SDH activity in a dose-dependent manner. However, compared with control, the activity of SDH remained significantly lower in brain regions of treated rats despite the attenuation of inhibition by LC pretreatment (P<0.05). These data suggest protective effect of LC against 3-NPA-induced oxidative stress. It appears that the protective effect of LC against 3-NPA-induced oxidative stress is not mediated by the direct action of LC preventing the SDH inhibition but rather is achieved due to the actions of LC downstream of the SDH inhibition.
Binienda
Z K
ZK
Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR 72079, USA. zbinienda@nctr.fda.gov
Ali
S F
SF
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002331:Carnitine / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009574:Nitro Compounds; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors; D013482:Superoxide Dismutase / Q000378:metabolism
D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; D002374:Catalase; D013482:Superoxide Dismutase; D013385:Succinate Dehydrogenase; C015392:3-nitropropionic acid; D002331:Carnitine