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Assessment of 3-nitropropionic acid-evoked peripheral neuropathy in rats: neuroprotective effects of acetyl-l-carnitine and resveratrol.

Abstract
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.
AuthorsZbigniew K Binienda, Micheal A Beaudoin, Bobby Gough, Syed F Ali, Ashraf Virmani
JournalNeuroscience letters (Neurosci Lett) Vol. 480 Issue 2 Pg. 117-21 (Aug 16 2010) ISSN: 1872-7972 [Electronic] Ireland
PMID20542088 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightPublished by Elsevier Ireland Ltd.
Chemical References
  • Antioxidants
  • Environmental Pollutants
  • Neuroprotective Agents
  • Nitro Compounds
  • Propionates
  • Stilbenes
  • Acetylcarnitine
  • Resveratrol
  • 3-nitropropionic acid
Topics
  • Acetylcarnitine (pharmacology, therapeutic use)
  • Animals
  • Antioxidants (pharmacology, therapeutic use)
  • Axons (drug effects, pathology)
  • Environmental Pollutants (toxicity)
  • Male
  • Nerve Degeneration (chemically induced, pathology, physiopathology)
  • Neural Conduction (drug effects)
  • Neuroprotective Agents (pharmacology, therapeutic use)
  • Nitro Compounds (toxicity)
  • Peripheral Nervous System Diseases (chemically induced, drug therapy, pathology)
  • Propionates (toxicity)
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol
  • Sciatic Nerve (drug effects, pathology, physiopathology)
  • Stilbenes (pharmacology, therapeutic use)

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