Effect of L-carnitine pretreatment on 3-nitropropionic acid-induced inhibition of rat brain succinate dehydrogenase activity.
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 mitochondrial succinate dehydrogenase (SDH). In the present study, activity of SDH was measured in order to evaluate neuroprotective effects of LC against the 3-NPA-induced neurotoxicity. Male, CD Sprague-Dawley rats, three months old, were injected with either 50 or 100 mg/kg of LC, i.p., 30 min prior to 3-NPA (30 mg/kg, s.c.) or with 3-NPA alone. The activity of brain SDH was quantified spectrophotometrically in caudate nucleus (CN), frontal cortex (FC), and hippocampus (HIP) 60 min after the 3-NPA injection. The SDH activity in the animals treated with 3-NPA alone was 38% (CN), 50% (FC), and 36% (HIP) that of saline controls. Pretreatment with LC prior to 3-NPA injection attenuated decreases of SDH activity by approximately 15 and 29% (LC low and high dose, respectively). Despite the attenuation of SDH inhibition, the activity of SDH in these regions remained significantly lower in treated than in control rats (p < 0.05). It appears that the protective effect of LC against 3-NPA-induced oxidative stress cannot be explained by the direct action of LC to interfere with the SDH inhibition but are rather achieved by LC actions downstream of the SDH inhibition.
Binienda
Z K
ZK
Division of Neurotoxicology, National Center for Toxicological Research/FDA, HFT-132, FDA/NCTR, Jefferson, AR 72079-9502, USA. zbinienda@nctr.fda.gov
Sadovova
N V
NV
Rountree
R L
RL
Scallet
A C
AC
Ali
S F
SF
D000818:Animals; D002331:Carnitine / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000187:drug effects / Q000201:enzymology; D003292:Convulsants / Q000633:toxicity*; D005625:Frontal Lobe / Q000187:drug effects / Q000201:enzymology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D009574:Nitro Compounds; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013385:Succinate Dehydrogenase / Q000187:drug effects* / Q000378:metabolism
D003292:Convulsants; D009574:Nitro Compounds; D011422:Propionates; D013385:Succinate Dehydrogenase; C015392:3-nitropropionic acid; D002331:Carnitine