Assessment of 3-nitropropionic acid-evoked peripheral neuropathy in rats: neuroprotective effects of acetyl-l-carnitine and resveratrol.
Oxidative stress and secondary excitotoxicity, due to cellular energy deficit, are major factors playing roles in 3-nitropropionic acid (3-NPA) induced mitochondrial dysfunction. Acute or chronic exposure to 3-NPA also leads to neuronal degeneration in different brain regions. The present study quantitatively assessed peripheral neuropathy induced by chronic exposure to 3-NPA in rats. The neuroprotective abilities of two antioxidants, acetyl-l-carnitine and resveratrol, were investigated as well. Rats were exposed for up to four weeks to 3-NPA alone or 3-NPA combined with acetyl-l-carnitine or resveratrol, administered peripherally. The experimental outcome was evaluated by neurophysiological, histological, and morphometric analyses. Rats exposed to 3-NPA developed hind limb paresis. Furthermore, a significant decrease in motor nerve conduction velocity (MCV) was detected in tail nerves and axonal degeneration in sciatic nerves (p<0.05). Treatment with resveratrol prevented the functional effects of 3-NPA exposure, whereas treatment with acetyl-l-carnitine, preventing paresis, was not effective to MCV and morphological changes. These data suggest that resveratrol is a good candidate for treatment of metabolic neuropathy. The experimental outcome of this study shows that chronic treatment with 3-NPA in rats is relevant in development of an experimental model of toxic neuropathy.
Binienda
Zbigniew K
ZK
Division of Neurotoxicology, National Center for Toxicological Research/FDA, AR 72079, USA. zbigniew.binienda@fda.hhs.gov
Beaudoin
Micheal A
MA
Gough
Bobby
B
Ali
Syed F
SF
Virmani
Ashraf
A
D000108:Acetylcarnitine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001369:Axons / Q000187:drug effects / Q000473:pathology; D004785:Environmental Pollutants / Q000633:toxicity*; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D009431:Neural Conduction / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009574:Nitro Compounds / Q000633:toxicity*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D004785:Environmental Pollutants; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; D013267:Stilbenes; D000108:Acetylcarnitine; D000077185:Resveratrol; C015392:3-nitropropionic acid