title: Subchronic effects of nasally instilled diesel exhaust particulates on the nasal and airway epithelia in mice.
abstract: Diesel exhaust is the major source of ultrafine particles released during traffic-related pollution. Subjects with chronic respiratory diseases are at greater risk for exacerbations during exposure to air pollution. This study evaluated the effects of subchronic exposure to a low-dose of diesel exhaust particles (DEP). Sixty male BALB/c mice were divided into two groups: (a) Saline: nasal instillation of saline (n = 30); and (b) DEP: nasal instillation of 30 microg of DEP/10 microl of saline (n = 30). Nasal instillations were performed 5 days a week, over 30 and 60 days. Animals were anesthetized with pentobarbital sodium (50 mg/kg intraperitoneal [i.p.]) and sacrificed by exsanguination. Bronchoalveolar lavage (BAL) fluid was performed to evaluate the inflammatory cell count and the concentrations of the interleukin (IL)-4, IL-10, and IL-13 by enzyme-linked immunosorbent assay (ELISA). The gene expression of oligomeric mucus/gel-forming (Muc5ac) was evaluated by real-time polymerase chain reaction (PCR). Histological analysis in the nasal septum and bronchioles was used to evaluate the bronchial and nasal epithelium thickness as well as the acidic and neutral nasal mucus content. The saline group (30 and 60 days) did not show any changes in any of the parameters. However, the instillation of DEP over 60 days increased the expression of Muc5ac in the lungs and the acid mucus content in the nose compared with the 30-day treatment, and it increased the total leukocytes in the BAL and the nasal epithelium thickness compared with saline for 60 days. Cytokines concentrations in the BAL were detectable, with no differences among the groups. Our data suggest that a low-dose of DEP over 60 days induces respiratory tract inflammation.
authors.affiliation: Laboratory of Experimental Atmospheric Pollution (LPAE), University of São Paulo, Avenida Dr. Arnaldo 455, São Paulo, Brazil.
authors.forename: K
authors.initials: K
authors.lastname: Yoshizaki
authors.forename: J M
authors.initials: JM
authors.lastname: Brito
authors.forename: A C
authors.initials: AC
authors.lastname: Toledo
authors.forename: N K
authors.initials: NK
authors.lastname: Nakagawa
authors.forename: V S
authors.initials: VS
authors.lastname: Piccin
authors.forename: M S
authors.initials: MS
authors.lastname: Junqueira
authors.forename: E M
authors.initials: EM
authors.lastname: Negri
authors.forename: A L N
authors.initials: AL
authors.lastname: Carvalho
authors.forename: A P Ligeiro de
authors.initials: AP
authors.lastname: Oliveira
authors.forename: W Tavares de
authors.initials: WT
authors.lastname: Lima
authors.forename: P H N
authors.initials: PH
authors.lastname: Saldiva
authors.forename: T
authors.initials: T
authors.lastname: Mauad
authors.forename: M
authors.initials: M
authors.lastname: Macchione
mesh_terms: D000281:Administration, Intranasal; D000393:Air Pollutants / Q000009:adverse effects; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D052638:Particulate Matter / Q000008:administration & dosage* / Q000009:adverse effects*; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000473:pathology*; D001335:Vehicle Emissions
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D001335:Vehicle Emissions