Effects of a cyclooxygenase-2 preferential inhibitor in young healthy dogs exposed to air pollution: a pilot study.
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.
Calderón-Garcidueñas
Lilian
L
Instituto Nacional de Pediatría, Mexico City, Mexico. lilian.calderon-garciduenas@umontana.edu
Mora-Tiscareño
Antonieta
A
Gómez-Garza
Gilberto
G
Carrasco-Portugal
Miriam Del C
Mdel C
Pérez-Guillé
Beatriz
B
Flores-Murrieta
Francisco J
FJ
Pérez-Guillé
Gabriela
G
Osnaya
Norma
N
Juárez-Olguín
Hugo
H
Monroy
Maria E
ME
Monroy
Silvia
S
González-Maciel
Angelica
A
Reynoso-Robles
Rafael
R
Villarreal-Calderon
Rafael
R
Patel
Sarjubhai A
SA
Kumarathasan
Prem
P
Vincent
Renaud
R
Henríquez-Roldán
Carlos
C
Torres-Jardón
Ricardo
R
Maronpot
Robert R
RR
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
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