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Effect of resveratrol on 3-nitropropionic acid-induced biochemical and behavioural changes: possible neuroprotective mechanisms.

Abstract
Huntington's disease is a progressive, degenerative disease characterized by abnormal body movements called chorea, and a reduction of various mental abilities. 3-Nitropropionic acid, an inhibitor of complex II of the electron transport chain, causes Huntington's disease-like symptoms in rodents. Recently, it has been reported that oxidative stress, which is one of the pathological hallmarks of various neurodegenerative disorders, also plays an important role in the pathogenesis of Huntington's disease. The present study was designed to investigate effects of resveratrol, an antioxidant with cyclooxygenase I inhibitory activity, in the 3-nitropropionic acid-induced model of Huntington's disease. Intraperitoneal administration of 3-nitropropionic acid (20 mg/kg for 4 days) caused significant loss of body weight, a decline in motor function (locomotor activity, movement pattern and vacuous chewing movements) and poor retention of memory. Repeated treatment with resveratrol (5 and 10 mg/kg, orally), once daily for a period of 8 days beginning 4 days prior to 3-nitropropionic acid administration, significantly improved the 3-nitropropionic acid-induced motor and cognitive impairment. Biochemical analysis revealed that systemic 3-nitropropionic acid administration significantly increased lipid peroxidation, nitrite levels, and depleted reduced glutathione levels, and decreased succinate dehydrogenase activity in the brains of rats. The results of the present study indicate that resveratrol (5 and 10 mg/kg, orally) significantly reversed 3-nitropropionic acid-induced motor and cognitive impairment, and that the beneficial effects of resveratrol might be attributed to its antioxidant activity.
AuthorsPuneet Kumar, Satyanaryana Sreenivasulu Venketswera Padi, Pattipati Sreenivasulu Naidu, Anil Kumar
JournalBehavioural pharmacology (Behav Pharmacol) Vol. 17 Issue 5-6 Pg. 485-92 (Sep 2006) ISSN: 0955-8810 [Print] England
PMID16940769 (Publication Type: Journal Article)
Chemical References
  • Antioxidants
  • Neuroprotective Agents
  • Neurotoxins
  • Nitro Compounds
  • Propionates
  • Stilbenes
  • Succinate Dehydrogenase
  • Glutathione
  • Resveratrol
  • 3-nitropropionic acid
Topics
  • Animals
  • Antioxidants (pharmacology)
  • Behavior, Animal (drug effects)
  • Brain (drug effects, physiopathology)
  • Cell Survival (drug effects, physiology)
  • Glutathione (metabolism)
  • Huntington Disease (chemically induced, physiopathology)
  • Injections, Intraperitoneal
  • Lipid Peroxidation (drug effects)
  • Male
  • Motor Activity (drug effects, physiology)
  • Neurons (drug effects, physiology)
  • Neuroprotective Agents (pharmacology)
  • Neurotoxins (toxicity)
  • Nitro Compounds (toxicity)
  • Propionates (toxicity)
  • Rats
  • Rats, Wistar
  • Resveratrol
  • Retention, Psychology (drug effects, physiology)
  • Stereotyped Behavior (drug effects, physiology)
  • Stilbenes (pharmacology)
  • Succinate Dehydrogenase (metabolism)

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