title: Effects of a cyclooxygenase-2 preferential inhibitor in young healthy dogs exposed to air pollution: a pilot study.
abstract: Residency in cities with high air pollution is associated with neuroinflammation and neurodegeneration in healthy children, young adults, and dogs. Nonsteroidal anti-inflammatory drugs may offer neuroprotection. The authors measured the plasma concentrations of 3-nitrotyrosine and the cerebro-spinal-fluid concentrations of prostaglandin E2 metabolite and the oligomeric form of amyloid derived diffusible ligand; measured the mRNA expression of cyclooxygenase-2, interleukin 1beta, CD14, and Aquaporin-4 in target brain areas; and evaluated brain MRI, cognition, and neuropathology in 8 dogs treated with a preferential cyclooxygenase-2 inhibitor (Nimesulide) versus 7 untreated litter-matched Mexico City dogs. Nimesulide significantly decreased nitrotyrosine in plasma (p < .0001), frontal gray IL1beta (p = .03), and heart IL1beta (p = .02). No effect was seen in mRNA COX2, amyloid, and PGE2 in CSF or the MRI white matter lesions. All exposed dogs exhibited olfactory bulb and frontal accumulation of Abeta(42) in neurons and blood vessels and frontal vascular subcortical pathology. White matter hyperintense MRI frontal lesions were seen in 4/6 non-treated and 6/8 treated dogs. Nonsteroidal anti-inflammatory drugs may offer limited neuroprotection in the setting of severe air pollution exposures. The search for potentially beneficial drugs useful to ameliorate the brain effects of pollution represents an enormous clinical challenge.
authors.affiliation: Instituto Nacional de Pediatría, Mexico City, Mexico. lilian.calderon-garciduenas@umontana.edu
authors.forename: Lilian
authors.initials: L
authors.lastname: Calderón-Garcidueñas
authors.forename: Antonieta
authors.initials: A
authors.lastname: Mora-Tiscareño
authors.forename: Gilberto
authors.initials: G
authors.lastname: Gómez-Garza
authors.forename: Miriam Del C
authors.initials: Mdel C
authors.lastname: Carrasco-Portugal
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pérez-Guillé
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Flores-Murrieta
authors.forename: Gabriela
authors.initials: G
authors.lastname: Pérez-Guillé
authors.forename: Norma
authors.initials: N
authors.lastname: Osnaya
authors.forename: Hugo
authors.initials: H
authors.lastname: Juárez-Olguín
authors.forename: Maria E
authors.initials: ME
authors.lastname: Monroy
authors.forename: Silvia
authors.initials: S
authors.lastname: Monroy
authors.forename: Angelica
authors.initials: A
authors.lastname: González-Maciel
authors.forename: Rafael
authors.initials: R
authors.lastname: Reynoso-Robles
authors.forename: Rafael
authors.initials: R
authors.lastname: Villarreal-Calderon
authors.forename: Sarjubhai A
authors.initials: SA
authors.lastname: Patel
authors.forename: Prem
authors.initials: P
authors.lastname: Kumarathasan
authors.forename: Renaud
authors.initials: R
authors.lastname: Vincent
authors.forename: Carlos
authors.initials: C
authors.lastname: Henríquez-Roldán
authors.forename: Ricardo
authors.initials: R
authors.lastname: Torres-Jardón
authors.forename: Robert R
authors.initials: RR
authors.lastname: Maronpot
mesh_terms: D000397:Air Pollution / Q000009:adverse effects*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D001921:Brain / Q000033:anatomy & histology / Q000473:pathology; D016009:Chi-Square Distribution; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D004285:Dogs / Q000378:metabolism*; D005625:Frontal Lobe / Q000378:metabolism; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008800:Mexico; D009297:Nasal Mucosa / Q000378:metabolism; D010126:Ozone / Q000009:adverse effects; D010865:Pilot Projects; D011458:Prostaglandins E / Q000378:metabolism; D018709:Statistics, Nonparametric; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D051401:Aquaporin 4; D052246:Cyclooxygenase 2 Inhibitors; D053583:Interleukin-1beta; D018950:Lipopolysaccharide Receptors; D011458:Prostaglandins E; D013449:Sulfonamides; D014443:Tyrosine; D010126:Ozone; D051546:Cyclooxygenase 2; C012655:nimesulide