TY - JOUR
T1 - Effects of a Cyclooxygenase-2 Preferential Inhibitor in Young Healthy Dogs Exposed to Air Pollution
T2 - A Pilot Study
AU - Calderón-Garcidueñas, Lilian
AU - Mora-Tiscareño, Antonieta
AU - Gómez-Garza, Gilberto
AU - Carrasco-Portugal, Miriam Del C.
AU - Pérez-Guillé, Beatriz
AU - Flores-Murrieta, Francisco J.
AU - Pérez-Guillé, Gabriela
AU - Osnaya, Norma
AU - Juárez-Olguín, Hugo
AU - Monroy, Maria E.
AU - Monroy, Silvia
AU - González-Maciel, Angelica
AU - Reynoso-Robles, Rafael
AU - Villarreal-Calderon, Rafael
AU - Patel, Sarjubhai A.
AU - Kumarathasan, Prem
AU - Vincent, Renaud
AU - Henríquez-Roldán, Carlos
AU - Torres-Jardón, Ricardo
AU - Maronpot, Robert R.
PY - 2009/8
Y1 - 2009/8
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - Nimesulide
KW - air pollution
KW - brain MRI
KW - cerebrospinal fluid
KW - dogs
KW - neuroinflammation
KW - neuroprotection
UR - http://www.scopus.com/inward/record.url?scp=70350450330&partnerID=8YFLogxK
U2 - 10.1177/0192623309340277
DO - 10.1177/0192623309340277
M3 - Artículo
SN - 0192-6233
VL - 37
SP - 644
EP - 660
JO - Toxicologic Pathology
JF - Toxicologic Pathology
IS - 5
ER -