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.

journal_name

Toxicol Pathol

journal_title

Toxicologic pathology

authors

Calderón-Garcidueñas L,Mora-Tiscareño A,Gómez-Garza G,Carrasco-Portugal Mdel C,Pérez-Guillé B,Flores-Murrieta FJ,Pérez-Guillé G,Osnaya N,Juárez-Olguín H,Monroy ME,Monroy S,González-Maciel A,Reynoso-Robles R,Villarreal-Calderon

doi

10.1177/0192623309340277

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

644-60

issue

5

eissn

0192-6233

issn

1533-1601

pii

37/5/644

journal_volume

37

pub_type

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