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Licofelone attenuates MPTP-induced neuronal toxicity: behavioral, biochemical and cellular evidence.

Abstract
Neuroinflammation and oxidative stress play critical role in the pathophysiology of neurodegenerative diseases including Parkinson's disease (PD). Recent reports indicate the beneficial effect of anti-inflammatory drugs in attenuating the progression of PD. Therefore, the present study is aimed to evaluate the possible role of licofelone, a dual COX/LOX-inhibitor against MPTP-induced neurotoxicity in mice. Administration of MPTP (40 mg/kg in divided doses of four injections of 10 mg/kg, i.p. each at 1 h interval) significantly impaired locomotor activity and induced catatonia, oxidative damage (elevated levels of lipid peroxidation, superoxide anion and nitrite, and decreased levels of non-protein thiols) as compared with vehicle-treated animals. Biochemical studies revealed significant alterations in mitochondrial enzyme complex activities (decreased complex-I activity and mitochondrial viability) and increased levels of caspase-3 and NF-κB/p65 as compared to vehicle treated group. Licofelone (2.5, 5 or 10 mg/kg/day, p.o.) treatment for 7 days significantly improved locomotor activity, attenuated the severity of catatonia, oxidative damage and restored mitochondrial enzyme complex activity as compared to MPTP-treated group. Licofelone treatment also attenuated the expression of apoptotic factor (caspase-3) and transcription factor (NF-κB/p65) as compared to MPTP-treated group. The findings of the present study suggest that licofelone (dual inhibitor of COX and LOX) represents a new class of anti-inflammatory agent which may provide a novel therapeutic alternative for the treatment and management of PD.
AuthorsAmit Gupta, Anil Kumar, S K Kulkarni
JournalInflammopharmacology (Inflammopharmacology) Vol. 18 Issue 5 Pg. 223-32 (Oct 2010) ISSN: 1568-5608 [Electronic] Switzerland
PMID20697819 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents
  • Cyclooxygenase Inhibitors
  • Lipoxygenase Inhibitors
  • NF-kappa B
  • Neuroprotective Agents
  • Nitrites
  • Pyrroles
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Caspase 3
  • licofelone
Topics
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Anti-Inflammatory Agents (administration & dosage, pharmacology)
  • Behavior, Animal (drug effects)
  • Caspase 3 (metabolism)
  • Cyclooxygenase Inhibitors (administration & dosage, pharmacology)
  • Lipid Peroxidation
  • Lipoxygenase Inhibitors (administration & dosage, pharmacology)
  • MPTP Poisoning (metabolism, prevention & control, psychology)
  • Mice
  • Mitochondria (drug effects, enzymology)
  • Motor Activity (drug effects)
  • NF-kappa B (metabolism)
  • Neuroprotective Agents (administration & dosage, pharmacology)
  • Nitrites (metabolism)
  • Oxidative Stress (drug effects)
  • Pyrroles (administration & dosage, pharmacology)

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