RESUMEN
Chronic obstructive pulmonary disease (COPD) is associated with inflammatory cell reactions, tissue destruction and lung remodeling. Many signaling pathways for these phenomena are still to be identified. We developed a mouse model of COPD to evaluate some pathophysiological mechanisms acting during the initial stage of the disease. Forty-seven 6- to 8-week-old female C57/BL6 mice (approximately 22 g) were exposed for 2 months to cigarette smoke and/or residual oil fly ash (ROFA), a concentrate of air pollution. We measured lung mechanics, airspace enlargement, airway wall thickness, epithelial cell profile, elastic and collagen fiber deposition, and by immunohistochemistry transforming growth factor-β1 (TGF-β1), macrophage elastase (MMP12), neutrophils and macrophages. We observed regional airspace enlargements near terminal bronchioles associated with the exposure to smoke or ROFA. There were also increases in airway resistance and thickening of airway walls in animals exposed to smoke. In the epithelium, we noted a decrease in the ciliated cell area of animals exposed to smoke and an increase in the total cell area associated with exposure to both smoke and ROFA. There was also an increase in the expression of TGF-β1 both in the airways and parenchyma of animals exposed to smoke. However, we could not detect inflammatory cell recruitment, increases in MMP12 or elastic and collagen fiber deposition. After 2 months of exposure to cigarette smoke and/or ROFA, mice developed regional airspace enlargements and airway epithelium remodeling, although no inflammation or increases in fiber deposition were detected. Some of these phenomena may have been mediated by TGF-β1.
Asunto(s)
Animales , Femenino , Ratones , Remodelación de las Vías Aéreas (Respiratorias)/fisiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Mucosa Respiratoria/fisiopatología , Contaminación por Humo de Tabaco/efectos adversos , Arteriolas/patología , Colágeno/metabolismo , Modelos Animales de Enfermedad , Inmunohistoquímica , Músculo Liso Vascular/patología , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/patología , Mucosa Respiratoria/patología , Factores de Tiempo , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Chronic obstructive pulmonary disease (COPD) is associated with inflammatory cell reactions, tissue destruction and lung remodeling. Many signaling pathways for these phenomena are still to be identified. We developed a mouse model of COPD to evaluate some pathophysiological mechanisms acting during the initial stage of the disease. Forty-seven 6- to 8-week-old female C57/BL6 mice (approximately 22 g) were exposed for 2 months to cigarette smoke and/or residual oil fly ash (ROFA), a concentrate of air pollution. We measured lung mechanics, airspace enlargement, airway wall thickness, epithelial cell profile, elastic and collagen fiber deposition, and by immunohistochemistry transforming growth factor-ß1 (TGF-ß1), macrophage elastase (MMP12), neutrophils and macrophages. We observed regional airspace enlargements near terminal bronchioles associated with the exposure to smoke or ROFA. There were also increases in airway resistance and thickening of airway walls in animals exposed to smoke. In the epithelium, we noted a decrease in the ciliated cell area of animals exposed to smoke and an increase in the total cell area associated with exposure to both smoke and ROFA. There was also an increase in the expression of TGF-ß1 both in the airways and parenchyma of animals exposed to smoke. However, we could not detect inflammatory cell recruitment, increases in MMP12 or elastic and collagen fiber deposition. After 2 months of exposure to cigarette smoke and/or ROFA, mice developed regional airspace enlargements and airway epithelium remodeling, although no inflammation or increases in fiber deposition were detected. Some of these phenomena may have been mediated by TGF-ß1.
Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias)/fisiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Mucosa Respiratoria/fisiopatología , Contaminación por Humo de Tabaco/efectos adversos , Animales , Arteriolas/patología , Colágeno/metabolismo , Modelos Animales de Enfermedad , Femenino , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Músculo Liso Vascular/patología , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/patología , Mucosa Respiratoria/patología , Factores de Tiempo , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
The mechanisms by which PM(2.5) increases cardiovascular mortality are not fully identified. Autonomic alterations are the current main hypotheses. Our objective was to determine if PM(2.5) induces acute cardiac polarization alterations in healthy Wistar rats. PM(2.5) samples were collected on polycarbonate filters. Solutions containing 10, 20, and 50 microg PM(2.5) were administered by tracheal instillation. P wave duration decreased significantly at 20 microg (0.99 +/- 0.06, 0.95 +/- 0.06, and 0.96 +/- 0.07; P < 0.001), and 50 microg (0.98 +/- 0.06, 0.98 +/- 0.07, and 0.96 +/- 0.08; 60, 90 and 120 min, respectively) compared to blank filter solution (P < 0.001). PR interval duration decreased significantly at 20 microg (0.99 +/- 0.06, 0.98 +/- 0.07, and 0.97 +/- 0.08) and 50 microg (0.99 +/- 0.05, 0.97 +/- 0.0, and 0.95 +/- 0.05; 60, 90, and 120 min, respectively) compared to blank filter and 10 microg (P < 0.001). QRS interval duration decreased at 20 and 50 microg in relation to blank filter solution and 10 microg (P < 0.001). QT interval duration decreased significantly (P < 0.001) with time in animals receiving 20 microg (0.94 +/- 0.12, 0.88 +/- 0.14, and 0.88 +/- 0.11) and 50 microg (1.00 +/- 0.13; 0.97 +/- 0.11 and 0.98 +/- 0.16; 60, 90 and 120 min, respectively) compared to blank filter solution and 10 microg (P < 0.001). PM(2.5) induced reduced cardiac conduction time, within a short period, indicating that depolarization occurs more rapidly across ventricular tissue.
Asunto(s)
Electrocardiografía , Frecuencia Cardíaca , Material Particulado/toxicidad , Animales , Masculino , Ratas , Ratas WistarRESUMEN
The mechanisms by which PM2.5 increases cardiovascular mortality are not fully identified. Autonomic alterations are the current main hypotheses. Our objective was to determine if PM2.5 induces acute cardiac polarization alterations in healthy Wistar rats. PM2.5 samples were collected on polycarbonate filters. Solutions containing 10, 20, and 50 µg PM2.5 were administered by tracheal instillation. P wave duration decreased significantly at 20 µg (0.99 ± 0.06, 0.95 ± 0.06, and 0.96 ± 0.07; P < 0.001), and 50 µg (0.98 ± 0.06, 0.98 ± 0.07, and 0.96 ± 0.08; 60, 90 and 120 min, respectively) compared to blank filter solution (P < 0.001). PR interval duration decreased significantly at 20 µg (0.99 ± 0.06, 0.98 ± 0.07, and 0.97 ± 0.08) and 50 µg (0.99 ± 0.05, 0.97 ± 0.0, and 0.95 ± 0.05; 60, 90, and 120 min, respectively) compared to blank filter and 10 µg (P < 0.001). QRS interval duration decreased at 20 and 50 µg in relation to blank filter solution and 10 µg (P < 0.001). QT interval duration decreased significantly (P < 0.001) with time in animals receiving 20 µg (0.94 ± 0.12, 0.88 ± 0.14, and 0.88 ± 0.11) and 50 µg (1.00 ± 0.13; 0.97 ± 0.11 and 0.98 ± 0.16; 60, 90 and 120 min, respectively) compared to blank filter solution and 10 µg (P < 0.001). PM2.5 induced reduced cardiac conduction time, within a short period, indicating that depolarization occurs more rapidly across ventricular tissue.
Asunto(s)
Animales , Masculino , Ratas , Electrocardiografía , Frecuencia Cardíaca , Material Particulado/toxicidad , Ratas WistarRESUMEN
Several epidemiological studies have consistently demonstrated significant associations between ambient levels of particulate matter and lung injury and cardiovascular events with increased morbidity and mortality. Particle surrogates (PS), such as residual oil fly ash (ROFA), have been widely used in experimental studies aimed at characterizing the mechanisms of particle toxicity. Since PS composition varies depending on its source, studies with different types of PS may provide clues about the relative toxicity of the components generated by high-temperature combustion process. In this work, we have studied the effects of nasal instillation of increasing doses of different PS in mice: saline, carbon, and two types of particle surrogates. PS type A (PSA) was the ROFA collected from the waste incinerator of our university hospital; PS type B (PSB) was collected from the electrostatic precipitator of a large steel company and thus had an elevated metal content. After 24h, we analyzed hematological parameters, fibrinogen, bronchoalveolar lavage, bone marrow, and pulmonary histology. Nasal instillation of the two types of PS-induced leucopenia. PSB elicited a greater elevation of plasma fibrinogen levels. Bone marrow and pulmonary inflammatory changes were more intense for PSA. We concluded that the PS composition modulates acute inflammatory changes more significantly than the mass for these two types of PS.
Asunto(s)
Contaminantes Atmosféricos/toxicidad , Médula Ósea/efectos de los fármacos , Carbono/toxicidad , Pulmón/efectos de los fármacos , Metales/toxicidad , Animales , Médula Ósea/anatomía & histología , Lavado Broncoalveolar , Ceniza del Carbón , Electroforesis , Pruebas Hematológicas , Técnicas Histológicas , Pulmón/anatomía & histología , Masculino , Ratones , Ratones Endogámicos BALB C , Tamaño de la Partícula , Material ParticuladoRESUMEN
In this study, we explored the role of chronic exposure to urban air pollution in causing DNA damage (micronuclei frequency in peripheral erythrocytes) in rodents in vivo. Mice (n=20) were exposed to the urban atmosphere of São Paulo for 120 days (February to June 1999) and compared to animals (n=20) maintained in the countryside (Atibaia) for the same period. Daily levels of inhalable particles (PM10), CO, NO(2), and SO(2), were available for São Paulo. Occasional measurements of CO and O(3) were made in Atibaia, showing negligible levels of pollution in the area. The frequency of micronuclei (repeated-measures ANOVA) increased with aging, the highest values obtained for the 90th day of experiment (P<0.001). The exposure to urban air pollution elicited a significant (P=0.016) increase of micronuclei frequency, with no significant interaction with time of study. Associations (Spearman's correlation) between pollution levels of the week that precede blood sampling and micronuclei counts were observed in São Paulo. The associations between micronuclei counts and air pollution were particularly strong for pollutants associated with automotive emissions, such as CO (P=0.037), NO(2) (P<0.001), and PM10 (P<0.001). Our results support the concept that urban levels of air pollution may cause somatic mutations.