Pulmonary effects of inhaled diesel exhaust in aged mice

• Published in: Toxicology and applied pharmacology 2009-12, Vol.241 (3), p.283-293
• Main Authors: Sunil, Vasanthi R., Patel, Kinal J., Mainelis, Gediminas, Turpin, Barbara J., Ridgely, Sherritta, Laumbach, Robert J., Kipen, Howard M., Nazarenko, Yevgen, Veleeparambil, Manoj, Gow, Andrew J., Laskin, Jeffrey D., Laskin, Debra L.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Aerosols; Aging; Aging - physiology; ANIMALS; ANTIOXIDANTS; Antioxidants - metabolism; Biological and medical sciences; BODY; Bronchoalveolar Lavage Fluid - cytology; CHALCOGENIDES; CHEMICAL REACTIONS; Diesel exhaust; DIESEL FUELS; DISEASE INCIDENCE; DISTILLATES; ELEMENTS; ENERGY SOURCES; ENZYMES; FOSSIL FUELS; FUELS; GAS OILS; Immunohistochemistry; INFLAMMATION; Inflammation Mediators - metabolism; INHALATION; INTAKE; L-Lactate Dehydrogenase - metabolism; Lipocalin; LIQUID FUELS; Lung - drug effects; Lung - metabolism; Lung - pathology; Lung Diseases - chemically induced; Lung Diseases - metabolism; Lung Diseases - pathology; LUNGS; Male; MAMMALS; MANGANESE; Medical sciences; METALS; MICE; NITROGEN COMPOUNDS; NITROGEN OXIDES; Nitrogen Oxides - metabolism; ORGANIC COMPOUNDS; ORGANS; OXIDATION; Oxidative Stress - drug effects; OXIDES; OXIDOREDUCTASES; OXYGEN COMPOUNDS; Particle Size; Particulate Matter - analysis; Particulate Matter - toxicity; PATHOLOGICAL CHANGES; PETROLEUM; PETROLEUM DISTILLATES; PETROLEUM FRACTIONS; PETROLEUM PRODUCTS; PROTEINS; RESPIRATORY SYSTEM; Reverse Transcriptase Polymerase Chain Reaction; RODENTS; STRESSES; SUPEROXIDE DISMUTASE; Superoxide Dismutase - metabolism; SYMPTOMS; Toxicology; TRANSITION ELEMENTS; Tumor Necrosis Factor-alpha - metabolism; Vehicle Emissions - toxicity; VERTEBRATES
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2009.08.025

Pulmonary morbidity and mortality resulting from exposure to fine particulate matter (PM) increases with age. The present studies analyzed potential mechanisms underlying increased susceptibility of the elderly to PM using diesel exhaust (DE) as a model. Mice (2 m and 18 m) were exposed to DE (0, 300, and 1000 μg/m 3) for 3 h once (single) or 3 h/day for 3 days (repeated). Bronchoalveolar lavage fluid (BAL), serum and lung tissue were collected 0 and 24 h later. Exposure to DE resulted in structural alterations in the lungs of older but not younger mice, including patchy thickening of the alveolar septa and inflammatory cell localization in alveolar spaces. These effects were most pronounced 24 h after a single exposure to the higher dose of DE. Significant increases in BAL nitrogen oxides were also noted in older mice, as well as expression of lipocalin 24p3, an oxidative stress marker in the lung with no effects in younger mice. Following DE inhalation, expression of Tumor Necrosis Factor alpha (TNFα) was upregulated in lungs of both younger and older mice; however, this was attenuated in older animals. Whereas exposure to DE resulted in increases in lung Interleukin-6 (IL-6) expression in both older and younger mice, IL-8 increased only in older animals. In younger mice, constitutive expression of manganese superoxide dismutase (MnSOD) decreased after DE exposure, while in older mice, constitutive MnSOD was not detectable and DE had no effect on expression of this antioxidant. Taken together, these results suggest that altered generation of inflammatory mediators and MnSOD may contribute to increased susceptibility of older mice to inhaled DE.