Effects of a Cyclooxygenase-2 Preferential Inhibitor in Young Healthy Dogs Exposed to Air Pollution: A Pilot Study

Lilian Calderón-Garcidueñas, Antonieta Mora-Tiscareño, Gilberto Gómez-Garza, Miriam Del C. Carrasco-Portugal, Beatriz Pérez-Guillé, Francisco J. Flores-Murrieta, Gabriela Pérez-Guillé, Norma Osnaya, Hugo Juárez-Olguín, Maria E. Monroy, Silvia Monroy, Angelica González-Maciel, Rafael Reynoso-Robles, Rafael Villarreal-Calderon, Sarjubhai A. Patel, Prem Kumarathasan, Renaud Vincent, Carlos Henríquez-Roldán, Ricardo Torres-Jardón, Robert R. Maronpot

Research output: Contribution to journalArticlepeer-review

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 1β, 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 IL1β (p = 03), and heart IL1β (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 Aβ42 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.

Original languageEnglish
Pages (from-to)644-660
Number of pages17
JournalToxicologic Pathology
Volume37
Issue number5
DOIs
StatePublished - Aug 2009

Keywords

  • Alzheimer’s disease
  • Nimesulide
  • air pollution
  • brain MRI
  • cerebrospinal fluid
  • dogs
  • neuroinflammation
  • neuroprotection

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