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1.
PLoS One ; 15(1): e0228393, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32004356

RESUMO

Chronic exposure to ambient levels of air pollution induces respiratory illness exacerbation by increasing inflammatory responses and apoptotic cells in pulmonary tissues. The ineffective phagocytosis of these apoptotic cells (efferocytosis) by macrophages has been considered an important factor in these pathological mechanisms. Depending on microenvironmental stimuli, macrophages can assume different phenotypes with different functional actions. M1 macrophages are recognized by their proinflammatory activity, whereas M2 macrophages play pivotal roles in responding to microorganisms and in efferocytosis to avoid the progression of inflammatory conditions. To verify how exposure to air pollutants interferes with macrophage polarization in emphysema development, we evaluated the different macrophage phenotypes in a PPE- induced model with the exposure to diesel exhaust particles. C57BL/6 mice received intranasal instillation of porcine pancreatic elastase (PPE) to induce emphysema, and the control groups received saline. Both groups were exposed to diesel exhaust particles or filtered air for 60 days according to the groups. We observed that both the diesel and PPE groups had an increase in alveolar enlargement, collagen and elastic fibers in the parenchyma and the number of macrophages, lymphocytes and epithelial cells in BAL, and these responses were exacerbated in animals that received PPE instillation prior to exposure to diesel exhaust particles. The same response pattern was found inCaspase-3 positive cell analysis, attesting to an increase in cell apoptosis, which is in agreement with the increase in M2 phenotype markers, measured by RT-PCR and flow cytometry analysis. We did not verify differences among the groups for the M1 phenotype. In conclusion, our results showed that both chronic exposure to diesel exhaust particles and PPE instillation induced inflammatory conditions, cell apoptosis and emphysema development, as well as an increase in M2 phenotype macrophages, and the combination of these two factors exacerbated these responses. The predominance of the M2-like phenotype likely occurred due to the increased demand for efferocytosis. However, M2 macrophage activity was ineffective, resulting in emphysema development and worsening of symptoms.


Assuntos
Poluentes Atmosféricos/toxicidade , Macrófagos/metabolismo , Elastase Pancreática/efeitos adversos , Enfisema Pulmonar/imunologia , Emissões de Veículos/toxicidade , Administração Intranasal , Animais , Apoptose , Líquido da Lavagem Broncoalveolar/imunologia , Estudos de Casos e Controles , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Elastase Pancreática/administração & dosagem , Enfisema Pulmonar/induzido quimicamente
2.
Environ Pollut ; 253: 667-679, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31330358

RESUMO

Many cities fail to meet air quality standards, which results in increased risk for pulmonary disorders, including asthma. Human and experimental studies have shown that diesel exhaust (DE) particles are associated with worsening of allergic asthma. Biodiesel (BD), a cleaner fuel from renewable sources, was introduced in the eighties. Because of the reduction in particulate matter (PM) emissions, BD was expected to cause fewer adverse pulmonary effects. However, only limited data on the effect of BD emissions in asthma are available. OBJECTIVE: Determine whether BD exhaust exposure in allergic sensitized mice leads to different effects on inflammatory and functional responses compared to DE exposure. METHODS: Balb/C mice were orotracheally sensitized with House Dust Mite (HDM) or a saline solution with 3 weekly instillations. From day 9 until day 17 after sensitization, they were exposed daily to filtered air (FA), DE and BD exhaust (concentration: 600 µg/m3 PM2.5). Lung function, bronchoalveolar lavage fluid (BALF) cell counts, cytokine levels (IL-2, IL-4, IL-5, IL-17, TNF-α, TSLP) in the BALF, peribronchiolar eosinophils and parenchymal macrophages were measured. RESULTS: HDM-sensitized animals presented increased lung elastance (p = 0.046), IgG1 serum levels (p = 0.029), peribronchiolar eosinophils (p = 0.028), BALF levels of total cells (p = 0.020), eosinophils (p = 0.028), IL-5 levels (p = 0.002) and TSLP levels (p = 0.046) in BALF. DE exposure alone increased lung elastance (p = 0.000) and BALF IL-4 levels (p = 0.045), whereas BD exposure alone increased BALF TSLP levels (p = 0.004). BD exposure did not influence any parameters after HDM challenge, while DE exposed animals presented increased BALF levels of total cells (p = 0.019), lymphocytes (p = 0.000), neutrophils (p = 0.040), macrophages (p = 0.034), BALF IL-4 levels (p = 0.028), and macrophagic inflammation in the lung tissue (p = 0.037), as well as decreased IgG1 (p = 0.046) and IgG2 (p = 0.043) levels when compared to the HDM group. CONCLUSION: The results indicate more adverse pulmonary effects of DE compared to BD exposure in allergic sensitized animals.


Assuntos
Biocombustíveis/toxicidade , Emissões de Veículos/toxicidade , Alérgenos , Animais , Asma/induzido quimicamente , Biocombustíveis/análise , Líquido da Lavagem Broncoalveolar , Citocinas , Modelos Animais de Doenças , Humanos , Inflamação/induzido quimicamente , Interleucina-17 , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos , Material Particulado/efeitos adversos , Testes de Toxicidade , Emissões de Veículos/análise
3.
Sci Total Environ ; 628-629: 1223-1233, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30045544

RESUMO

Biodiesel is a renewable energy source that reduces particle emission, but few studies have assessed its effects. To assess the effects of acute inhalation of two doses (600 and 1200 µg/m3) of diesel (DE) and biodiesel (BD) fuels on the inflammatory pulmonary and systemic profile of mice. Animals were exposed for 2 h in an inhalation chamber inside the Container Laboratory for Fuels. Heart rate, heart rate variability (HRV) and blood pressure were determined 30 min after exposure. After 24 h, we analyzed the lung inflammation using bronchoalveolar lavage fluid (BALF); neutrophil and macrophage quantification in the lung parenchyma was performed, and blood and bone marrow biomarkers as well as receptor of endothelin-A (ET-Ar), receptor of endothelin-B (ET-Br), vascular cell adhesion molecule 1 (VCAM-1), inducible nitric oxide synthase (iNOs) and isoprostane (ISO) levels in the pulmonary vessels and bronchial epithelium were evaluated. HRV increased for BD600, D600 and D1200 compared to filtered air (FA). Both fuels (DE and BD) produced alterations in red blood cells independent of the dose. BALF from the BD600 and BD1200 groups showed an increase in neutrophils compared to those of the FA group. Numeric density of the polymorphonuclear and mononuclear cells was elevated with BD600 compared to FA. In the peribronchiolar vessels, there was an increase in ET-Ar and ET-Br expression following BD600 compared to FA; and there was a reduction in the iNOs expression for BD1200 and the VCAM-1 for D1200 compared to FA. In the bronchial epithelium, there was an increase in ETAr at BD600, ET-Br at two doses (600 and 1200 µg/m3) of DE and BD, iNOs at D600 and VCAM-1 at BD1200 and D600; all groups were compared to the FA group. Acute exposure to DE and BD derived from sewage methyl esters triggered pulmonary and cardiovascular inflammatory alterations in mice.


Assuntos
Poluentes Atmosféricos/toxicidade , Biocombustíveis/toxicidade , Pneumonia/induzido quimicamente , Testes de Toxicidade Aguda , Emissões de Veículos/toxicidade , Animais , Biomarcadores/metabolismo , Líquido da Lavagem Broncoalveolar , Exposição por Inalação , Masculino , Camundongos
4.
Environ Sci Pollut Res Int ; 25(3): 2683-2690, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29134526

RESUMO

The present study evaluated the water quality of a polluted pond through the analysis of in vitro mucociliary transport, hematological parameters, and biomarkers of cyto-genotoxicity in the Nile tilapia (Oreochromis niloticus). Blood and mucus samples were collected from ten specimens from the polluted pond and from ten specimens from a control area. The fish were anesthetized with 3% benzocaine, mucus was collected directly from the gills, and blood was drawn from the caudal artery. Blood smears were stained using the May-Grünwald Giemsa process for the differential leukocyte counts and to determine the frequency of leukocytes, thrombocytes, erythroblasts, micronuclei, and nuclear abnormalities. The results revealed low transportability in vitro, a high percentage of monocytes and eosinophils, and increased frequency of leukocytes and nuclear abnormalities in fish from the polluted pond. However, the frequency of thrombocytes and erythroblasts and the percentage of lymphocytes and neutrophils were significantly lower. It is possible to conclude that changes in fish are due to poor water quality and that these non-destructive biomarkers can be used for the biomonitoring of aquatic environments vulnerable to contamination.


Assuntos
Ciclídeos/sangue , Dano ao DNA , Monitoramento Ambiental/métodos , Depuração Mucociliar/efeitos dos fármacos , Lagoas/química , Poluentes Químicos da Água/análise , Animais , Biomarcadores/análise , Ciclídeos/fisiologia , Eritrócitos/efeitos dos fármacos , Contagem de Leucócitos , Leucócitos/efeitos dos fármacos , Muco/química , Urbanização , Poluentes Químicos da Água/toxicidade
5.
Mem Inst Oswaldo Cruz ; 109(4): 484-7, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25075786

RESUMO

Antiretroviral therapy has been associated with side effects, either from the drug itself or in conjunction with the effects of human immunodeficiency virus infection. Here, we evaluated the side effects of the protease inhibitor (PI) indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment increased the hamster death rate and resulted in an increase in triglyceride, cholesterol and glucose serum levels and a reduction in anti-oxLDL auto-antibodies. The treatment led to histopathological alterations of the kidney and the heart. These results suggest that hamsters are an interesting model for the study of the side effects of antiretroviral drugs, such as PIs.


Assuntos
Gorduras na Dieta/sangue , Inibidores da Protease de HIV/farmacologia , Indinavir/farmacologia , Animais , Autoanticorpos/sangue , Biomarcadores/sangue , Glicemia/análise , Colesterol/sangue , Cricetinae , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Lipoproteínas LDL/efeitos dos fármacos , Modelos Animais , Triglicerídeos/sangue
6.
J Appl Physiol (1985) ; 117(5): 492-9, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-25012028

RESUMO

Ambient particles may undergo modifications to their chemical composition as a consequence of climatic variability. The determination of whether these changes modify the toxicity of the particles is important for the understanding of the health effects associated with particle exposure. The objectives were to determine whether low levels of particles promote cardiopulmonary effects, and to assess if the observed alterations are influenced by season. Mice were exposed to 200 µg/m(3) concentrated ambient particles (CAPs) and filtered air (FA) in cold/dry and warm/humid periods. Lung hyperresponsiveness, heart rate, heart rate variability, and blood pressure were evaluated 30 min after each exposure. After 24 h, blood and tissue samples were collected. During both periods (warm/humid and cold/dry), CAPs induced alterations in red blood cells and lung inflammation. During the cold/dry period, CAPs reduced the mean corpuscular volume levels and increased erythrocytes, hemoglobin, mean corpuscular hemoglobin concentration, and red cell distribution width coefficient variation levels compared with the FA group. Similarly, CAPs during the warm/humid period decreased mean corpuscular volume levels and increased erythrocytes, hemoglobin, hematocrit, and red cell distribution width coefficient variation levels compared with the FA group. CAPs during the cold/dry period increased the influx of neutrophils in the alveolar parenchyma. Short-term exposure to low concentrations of CAPs elicited modest but significant pulmonary inflammation and, to a lesser extent, changes in blood parameters. In addition, our data support the concept that changes in climate conditions slightly modify particle toxicity because equivalent doses of CAPs in the cold/dry period produced a more exacerbated response.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Hemodinâmica , Exposição por Inalação/efeitos adversos , Material Particulado/efeitos adversos , Mecânica Respiratória , Estações do Ano , Poluentes Atmosféricos/sangue , Animais , Brasil , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Material Particulado/sangue , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/sangue
7.
Mem. Inst. Oswaldo Cruz ; 109(4): 484-487, 03/07/2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-716314

RESUMO

Antiretroviral therapy has been associated with side effects, either from the drug itself or in conjunction with the effects of human immunodeficiency virus infection. Here, we evaluated the side effects of the protease inhibitor (PI) indinavir in hamsters consuming a normal or high-fat diet. Indinavir treatment increased the hamster death rate and resulted in an increase in triglyceride, cholesterol and glucose serum levels and a reduction in anti-oxLDL auto-antibodies. The treatment led to histopathological alterations of the kidney and the heart. These results suggest that hamsters are an interesting model for the study of the side effects of antiretroviral drugs, such as PIs.


Assuntos
Animais , Cricetinae , Gorduras na Dieta/sangue , Inibidores da Protease de HIV/farmacologia , Indinavir/farmacologia , Autoanticorpos/sangue , Biomarcadores/sangue , Glicemia/análise , Colesterol/sangue , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Lipoproteínas LDL/efeitos dos fármacos , Modelos Animais , Triglicerídeos/sangue
8.
Am J Respir Crit Care Med ; 178(7): 721-8, 2008 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-18596224

RESUMO

RATIONALE: Chronic exposure to air pollution has been associated with adverse effects on children's lung growth. OBJECTIVES: We analyzed the effects of chronic exposure to urban levels of particulate matter (PM) on selected phases of mouse lung development. METHODS: The exposure occurred in two open-top chambers (filtered and nonfiltered) placed 20 m from a street with heavy traffic in São Paulo, 24 hours/day for 8 months. There was a significant reduction of the levels of PM(2.5) inside the filtered chamber (filtered = 2.9 +/- 3.0 microg/m(3), nonfiltered = 16.8 +/- 8.3 microg/m(3); P = 0.001). At this exposure site, vehicular sources are the major components of PM(2.5) (PM

Assuntos
Poluentes Atmosféricos/efeitos adversos , Exposição por Inalação/efeitos adversos , Material Particulado/efeitos adversos , Alvéolos Pulmonares , Animais , Brasil , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Alvéolos Pulmonares/crescimento & desenvolvimento , Alvéolos Pulmonares/patologia , Testes de Função Respiratória , População Urbana , Emissões de Veículos
9.
Toxicol Sci ; 85(2): 898-905, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15746007

RESUMO

The mechanisms involved in the association between air pollution and increased cardiovascular morbidity are not fully understood. The objective of this study was to test the hypothesis that fine particulate matter (PM(2.5)) induces systemic inflammation and vasoconstriction of small arteries in the lung and heart of rats. Thirty-eight healthy Wistar rats were anesthetized, intubated, and submitted to the instillation of 1 ml of distilled water diluted in the following solution: blank filter, 100 microg and 500 microg of PM(2.5). PM(2.5) was collected in glass fiber filters with a high-volume sampler. The animals were sacrificed 24 h after instillation when blood, heart, and lung samples were collected for morphological and wet-to-dry weight ratio analysis. PM(2.5) consisted of the following elements: sulphur, arsenic, bromine, chlorine, cobalt, iron, lanthanum, manganese, antimony, scandium, and thorium. Total reticulocytes significantly increased at both PM(2.5) doses (p < 0.05) while hematocrit levels increased in the 500 microg group (p < 0.05). Quantification of segmented neutrophils and fibrinogen levels showed a significant decrease, while lymphocytes counting increased with 100 microg of PM(2.5) (p < 0.05). A significant dose-dependent decrease of intra-acinar pulmonary arteriole lumen/wall ratio (L/W) was observed in PM groups (p < 0.001). Peribronchiolar arterioles L/W showed a significant decrease in the 500 microg group (p < 0.001). A significant increase in heart wet-to-dry weight ratio was observed in the 500 microg group (p < 0.001). In conclusion, fine environment particles in the city of São Paulo promote pulmonary and cardiac histological alterations. Pulmonary vasculature was markedly affected by particle instillation, resulting in significant vasoconstriction in healthy rats.


Assuntos
Poluentes Atmosféricos/toxicidade , Coração/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Administração por Inalação , Animais , Artérias/patologia , Peso Corporal/efeitos dos fármacos , Brasil , Inflamação/induzido quimicamente , Inflamação/patologia , Pulmão/patologia , Masculino , Miocárdio/patologia , Tamanho do Órgão/efeitos dos fármacos , Tamanho da Partícula , Ratos , Ratos Wistar
10.
J. pneumol ; 28(1): 1-7, jan.-fev. 2002. ilus
Artigo em Português | LILACS | ID: lil-352727

RESUMO

Objetivo: Com a finalidade de estabelecer uma linha de pesquisa em cirurgia redutora de volume pulmonar, foi proposta a reprodução de um modelo experimental de enfisema em ratos através da instilação intratraqueal de papaína. Métodos: Foi feita a instilação orotraqueal de papaína (20mg/kg) dissolvida em 3,5ml/kg de solução fisiológica a 0,9 por cento. Após 40 dias da instilação, os animais foram submetidos a mecânica ventilatória, com medidas de elastância e resistência do sistema respiratório, e sacrificados com retirada dos pulmões. O tecido pulmonar dos animais foi analisado qualitativamente com coloração de hematoxilina-eosina e submetido à análise morfométrica com medida do diâmetro alveolar médio. O tecido pulmonar foi também submetido à coloração de resorcina-fucsina, para identificação de fibras elásticas, que foram quantificadas em septos alveolares através de análise digital de imagem. Resultados: A análise histológica dos pulmões dos animais submetidos à instilação de papaína mostrou um enfisema pan-acinar, com rotura de septos alveolares e hiperdistensão alveolar. A análise morfométrica revelou médias superiores de diâmetro alveolar médio nos pulmões dos animais submetidos à papaína (149,08mim e 100,56mim), em comparação com o grupo de solução fisiológica (64,08mim e 75,90mim). A quantificação de fibras elásticas de septos alveolares de animais tratados com papaína foi 70 por cento menor do que a de animais submetidos à solução fisiológica. A mecânica ventilatória não mostrou diferença na resistência do sistema respiratório de animais submetidos à papaína ou à solução fisiológica. Já no caso da elastância do sistema respiratório, esta foi menor nos animais do grupo com papaína, em comparação com o grupo com solução fisiológica, demonstrando comportamento funcional do grupo com papaína compatível com enfisema pulmonar, apresentando diminuição da capacidade de recolhimento elástico do tecido pulmonar. Conclusão: Foi possível reproduzir um modelo experimental de enfisema pulmonar pan-acinar em ratos, através da instilação de papaína pela árvore respiratória, com comprovação funcional e morfológica


Assuntos
Animais , Masculino , Ratos , Enfisema Pulmonar/induzido quimicamente , Papaína/administração & dosagem , Modelos Animais de Doenças , Enfisema Pulmonar/patologia , Instilação de Medicamentos , Ratos Wistar , Mecânica Respiratória , Tecido Elástico/patologia
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