title: Role of LOX/COX pathways in 3-nitropropionic acid-induced Huntington's disease-like symptoms in rats: protective effect of licofelone.
abstract: OBJECTIVE
  Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by a degeneration of striatal neurons. The possible role of COX and lipoxygenase (LOX) pathways has been well-documented in the pathology of several neurodegenerative disorders including HD. Licofelone is a competitive inhibitor of COX-1- and COX-2 and 5-LOX isoenzymes. Therefore, the present study was designed to investigate possible neuroinflammatory and apoptotic mechanisms in the neuroprotective effect of licofelone against 3-nitropropionic acid (3-NP)-induced HD-like symptoms in rats.
  
  
  METHODS
  Rats were administered 3-NP (10 mg·kg⁻¹ day⁻¹, i.p.) for 14 days. Licofelone (2.5, 5 and 10 mg·kg⁻¹, p.o.) was given once a day, 1 h before 3-NP treatment for 14 days. Body weight and behavioural parameters (locomotor and rotarod activity) were assessed on the 1st, 5th, 10th and 15th day post-3-NP administration. Malondialdehyde, nitrite concentration, endogenous antioxidant enzymes (superoxide dismutase and catalase levels), mitochondrial enzyme complexes, pro-inflammatory compounds (TNF-α, IL-6, NF-κB), PGs (PGE₂ and PGF(2α)) and caspase-3 activity were measured on day 15 in the striatum.
  
  
  RESULTS
  Systemic 3-NP treatment significantly reduced body weight, locomotor activity, oxidative defence, mitochondrial enzyme complex activities and increased TNF-α, IL-6, caspase-3 activity, NF-κB and PGE₂ and PGF(2α) levels in the striatum. Licofelone (2.5, 5 and 10 mg·kg⁻¹) significantly attenuated the impairment in behavioural, biochemical and mitochondrial, pro-inflammatory and pro-apoptotic markers as compared with vehicle-treated group.
  
  
  CONCLUSIONS
  The results demonstrate the involvement of pro-inflammatory compounds and the apoptotic cascade in the neuroprotective effect of licofelone against 3-NP-induced neurotoxicity.
authors.affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, India.
authors.forename: Puneet
authors.initials: P
authors.lastname: Kumar
authors.forename: Harikesh
authors.initials: H
authors.lastname: Kalonia
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D006816:Huntington Disease / Q000139:chemically induced / Q000201:enzymology* / Q000378:metabolism / Q000517:prevention & control*; D015850:Interleukin-6 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008084:Lipoxygenase / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009573:Nitrites / Q000378:metabolism; D009574:Nitro Compounds; D011422:Propionates; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015850:Interleukin-6; D016328:NF-kappa B; D018696:Neuroprotective Agents; D009573:Nitrites; D009574:Nitro Compounds; D011422:Propionates; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D013482:Superoxide Dismutase; D053148:Caspase 3; D015232:Dinoprostone; C088092:licofelone; C015392:3-nitropropionic acid