Effects of a Cyclooxygenase-2 Preferential Inhibitor in Young Healthy Dogs Exposed to Air Pollution: A Pilot Study
Open accessAbstract
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.
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Studies in animals have found that developmental exposure to air pollution is related to functional and structural brain effects.
“Studies in animals have also found that developmental exposure to air pollution is related to functional and structural brain effects [11–15].”
From A Systematic Review and Meta-Analysis of Multiple Airborne Pollutants and Autism Spectrum Disorder (2016) · cites this paper as [11]
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A Systematic Review and Meta-Analysis of Multiple Airborne Pollutants and Autism Spectrum Disorder
Lam, J., Sutton, P., Kalkbrenner, A., Windham, G., Halladay, A., Koustas, E., Lawler, C., Davidson, L., Daniels, N., Newschaffer, C., et al. (2016) · PLOS ONE · doi:10.1371/journal.pone.0161851 · Cited by 247 · see citing works
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- Authors
- Calderón-Garcidueñas, L., Mora-Tiscareño, A., Gómez-Garza, G., Carrasco-Portugal, M. D. C., Pérez-Guillé, B., Flores-Murrieta, F. J., Pérez-Guillé, G., Osnaya, N., Juárez-Olguín, H., Monroy, M. E., Monroy, S., González-Maciel, A., Reynoso-Robles, R., Villarreal-Calderon, R., Patel, S. A., Kumarathasan, P., Vincent, R., Henríquez-Roldán, C., Torres-Jardón, R., & Maronpot, R. R.
- Affiliations
- Instituto Nacional de Pediatría, Mexico City, Mexico
- Instituto Nacional de Pediatria (MX)
- Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico
- Instituto Nacional de Enfermedades Respiratorias, Escuela Superior de Medicina del Instituto Politécnico Nacional, Mexico City, Mexico
- Davidson Honors College, University of Montana, Missoula, MT, USA
- University of Montana (US)
- Inhalation Toxicology and Aerobiology Section, Healthy Environments and Consumer Safety Branch Health, Ottawa, Ontario, Canada
- University of Valparaíso (CL)
- Centro de Ciencias de la Atmósfera, Universidad Nacional Autónoma de México, Mexico City, Mexico
- Experimental Pathology Laboratories (US)
- ORCID
- Venue
- Toxicologic Pathology
- Publisher
- SAGE Publications
- Published
- 2009-07-28
- Volume
- 37
- Issue
- 5
- Pages
- 644-660
- ISSN
- 0192-6233 (ISSN-L)
- 1533-1601
- OpenAlex
- W2101492696
- Cited by
- 28
- References
- 4
- Citations by year
- 2025: 1 · 2024: 2 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 4 · 2016: 5 · 2015: 3 · 2012: 3
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Toxicologic Pathology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (0346458)
- Montana Board of Research and Commercialization Technology
- National Institute of Neurological Disorders and Stroke (K01NS046410)
- National Center for Research Resources (RR-015583, P20RR015583)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Air Quality and Health Impacts
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- air pollution, neuroinflammation, neuroprotection, COX-2 inhibitors, nimesulide, nonsteroidal anti-inflammatory drugs, nitrotyrosine, IL-1β, amyloid-beta, white matter hyperintensities, dogs, urban air pollution, neurodegeneration
- MeSH terms
- Air Pollution, Animals, Brain, Dogs, Frontal Lobe, Immunohistochemistry, Magnetic Resonance Imaging, Mexico, Nasal Mucosa, Ozone, Pilot Projects, Prostaglandins E, Sulfonamides, Tyrosine, Chi-Square Distribution, Amyloid beta-Peptides, Statistics, Nonparametric, Lipopolysaccharide Receptors, Aquaporin 4, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Interleukin-1beta
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