RESUMO
BACKGROUND: The Metropolitan Area of São Paulo has a unique composition of atmospheric pollutants, and positive correlations between exposure and the risk of diseases and mortality have been observed. Here we assessed the effects of ambient fine particulate matter (PM2.5) on genotoxic and global DNA methylation and hydroxymethylation changes, as well as the activities of antioxidant enzymes, in tissues of AJ mice exposed whole body to ambient air enriched in PM2.5, which was concentrated in a chamber near an avenue of intense traffic in São Paulo City, Brazil. RESULTS: Mice exposed to concentrated ambient PM2.5 (1 h daily, 3 months) were compared to in situ ambient air exposed mice as the study control. The concentrated PM2.5 exposed group presented increased levels of the oxidized nucleoside 8-oxo-7,8-dihydro-2'-deoxyguanosine in lung and kidney DNA and increased levels of the etheno adducts 1,N6-etheno-2'-deoxyadenosine and 1,N2-etheno-2'-deoxyguanosine in kidney and liver DNA, respectively. Apart from the genotoxic effects, the exposure to PM2.5 led to decreased levels of the epigenetic mark 5-hydroxymethylcytosine (5-hmC) in lung and liver DNA. Changes in lung, liver, and erythrocyte antioxidant enzyme activities were also observed. Decreased glutathione reductase and increased superoxide dismutase (SOD) activities were observed in the lungs, while the liver presented increased glutathione S-transferase and decreased SOD activities. An increase in SOD activity was also observed in erythrocytes. These changes are consistent with the induction of local and systemic oxidative stress. CONCLUSIONS: Mice exposed daily to PM2.5 at a concentration that mimics 24-h exposure to the mean concentration found in ambient air presented, after 3 months, increased levels of DNA lesions related to the occurrence of oxidative stress in the lungs, liver, and kidney, in parallel to decreased global levels of 5-hmC in lung and liver DNA. Genetic and epigenetic alterations induced by pollutants may affect the genes committed to cell cycle control, apoptosis, and cell differentiation, increasing the chance of cancer development, which merits further investigation.
Assuntos
Poluentes Atmosféricos/toxicidade , Dano ao DNA , Monitoramento Ambiental/métodos , Epigênese Genética/efeitos dos fármacos , Nanopartículas/toxicidade , Material Particulado/toxicidade , Animais , Brasil , Cidades , Metilação de DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Camundongos Endogâmicos , Especificidade de Órgãos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Tamanho da PartículaRESUMO
OBJECTIVES: To evaluate pulmonary function in the first and third trimesters of pregnancy and analyze the influence of parity and smoking on spirometry parameters. METHODS: This longitudinal prospective study included a cohort of 120 pregnant women. The inclusion criteria were as follows: singleton pregnancy, gestational age less than 13.86 weeks, and no preexisting maternal diseases. The exclusion criteria were as follows: change of address, abortion, and inadequate spirometry testing. ClinicalTrials.gov: NCT02807038. RESULTS: A decrease in values of forced vital capacity and forced expiratory volume were noted in the first second from the first to third trimester. In the first and third trimesters, multiparous women demonstrated lower absolute forced vital capacity and forced expiratory volume values in the first second compared with nulliparous women (p<0.0001 and p=0.001, respectively). Multiparous women demonstrated reduced forced expiratory flow in 25% to 75% of the maneuver compared with nulliparous women in the first (p=0.005) and third (p=0.031) trimesters. The absolute values of forced expiratory flow in 25% to 75%, forced expiratory volume in the first second and predicted peak expiratory flow values in the third trimester were higher in smokers compared with nonsmokers (p=0.042, p=0.039, p=0.024, and p=0.021, respectively). CONCLUSION: There was a significant reduction in forced vital capacity and forced expiratory volume values in the first second during pregnancy. Parity and smoking significantly influence spirometric variables.
Assuntos
Pulmão/fisiologia , Paridade/fisiologia , Fumar/fisiopatologia , Adulto , Fatores Etários , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Estudos Longitudinais , Gravidez , Primeiro Trimestre da Gravidez/fisiologia , Terceiro Trimestre da Gravidez/fisiologia , Estudos Prospectivos , Valores de Referência , Fumar/efeitos adversos , Espirometria , Estatísticas não Paramétricas , Capacidade Vital/fisiologia , Adulto JovemRESUMO
OBJECTIVES: To evaluate pulmonary function in the first and third trimesters of pregnancy and analyze the influence of parity and smoking on spirometry parameters. METHODS: This longitudinal prospective study included a cohort of 120 pregnant women. The inclusion criteria were as follows: singleton pregnancy, gestational age less than 13.86 weeks, and no preexisting maternal diseases. The exclusion criteria were as follows: change of address, abortion, and inadequate spirometry testing. ClinicalTrials.gov: NCT02807038. RESULTS: A decrease in values of forced vital capacity and forced expiratory volume were noted in the first second from the first to third trimester. In the first and third trimesters, multiparous women demonstrated lower absolute forced vital capacity and forced expiratory volume values in the first second compared with nulliparous women (p<0.0001 and p=0.001, respectively). Multiparous women demonstrated reduced forced expiratory flow in 25% to 75% of the maneuver compared with nulliparous women in the first (p=0.005) and third (p=0.031) trimesters. The absolute values of forced expiratory flow in 25% to 75%, forced expiratory volume in the first second and predicted peak expiratory flow values in the third trimester were higher in smokers compared with nonsmokers (p=0.042, p=0.039, p=0.024, and p=0.021, respectively). CONCLUSION: There was a significant reduction in forced vital capacity and forced expiratory volume values in the first second during pregnancy. Parity and smoking significantly influence spirometric variables.
Assuntos
Humanos , Feminino , Gravidez , Adulto , Adulto Jovem , Paridade/fisiologia , Fumar/fisiopatologia , Pulmão/fisiologia , Terceiro Trimestre da Gravidez/fisiologia , Primeiro Trimestre da Gravidez/fisiologia , Valores de Referência , Espirometria , Fumar/efeitos adversos , Capacidade Vital/fisiologia , Volume Expiratório Forçado/fisiologia , Estudos Prospectivos , Estudos Longitudinais , Fatores Etários , Estatísticas não ParamétricasRESUMO
PURPOSE: To investigate the effect of Botulinum toxin A (BoNTA) on skin flap viability in healthy, tobacco-exposed and diabetic rats. METHODS: Ninety male Wistar rats (250-300g) were randomly divided into six groups: control+saline (C1), control+BoNTA (C2), tobacco-exposed+saline (T1), tobacco-exposed+BoNTA (T2) diabetes+saline (D1) and diabetes+BoNTA (D2). A dorsal cutaneous flap (3×10cm) was performed. Survival area and total area of the flaps were measured. Lumen diameter, external arterial diameter and lumen/wall thickness ratio were recorded. RESULTS: Survival area increased in control group with BoNTA injection compared with control animals injected with saline (C2 x C1; 0.9±0.1 vs0.67±0.15, p= 0.001). A similar result was found in diabetes group injected with BontA (D2 x D1; 0.97±0.2 vs0.61±0.24, p=0.018). No difference was observed in skin flap viability in tobacco-exposed groups (T2 x T1; 0.74±0.24 vs 0.64±0.21, p=0.871). Lumen diameter (p= 0.004), external arterial diameter (p = 0.0046,) and lumen/wall thickness ratio (p= 0.003) were increased in diabetes+BoNTA-treated animals. This effect was not observed in control or in tobacco-exposed groups. CONCLUSIONS: Botulinum toxin A increased skin flap viability in control and diabetic rats on the seventh post-operative day. Increased lumen diameter, external arterial diameter, and lumen/wall thickness ratio were observed in the diabetes+BoNTA group. BoNTA had no effect in the tobacco-exposed group on the seventh postoperative day.
Assuntos
Toxinas Botulínicas Tipo A/farmacologia , Diabetes Mellitus Experimental/complicações , Fármacos Neuromusculares/farmacologia , Pele/efeitos dos fármacos , Retalhos Cirúrgicos , Poluição por Fumaça de Tabaco/efeitos adversos , Animais , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Masculino , Necrose , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Pele/patologia , Estreptozocina , Retalhos Cirúrgicos/patologia , Fatores de TempoRESUMO
PURPOSE:To investigate the effect of Botulinum toxin A (BoNTA) on skin flap viability in healthy, tobacco-exposed and diabetic rats.METHODS: Ninety male Wistar rats (250-300g) were randomly divided into six groups: control+saline (C1), control+BoNTA (C2), tobacco-exposed+saline (T1), tobacco-exposed+BoNTA (T2) diabetes+saline (D1) and diabetes+BoNTA (D2). A dorsal cutaneous flap (3×10cm) was performed. Survival area and total area of the flaps were measured. Lumen diameter, external arterial diameter and lumen/wall thickness ratio were recorded.RESULTS: Survival area increased in control group with BoNTA injection compared with control animals injected with saline (C2 x C1; 0.9±0.1 vs0.67±0.15, p= 0.001). A similar result was found in diabetes group injected with BontA (D2 x D1; 0.97±0.2 vs0.61±0.24, p=0.018). No difference was observed in skin flap viability in tobacco-exposed groups (T2 x T1; 0.74±0.24 vs 0.64±0.21, p=0.871). Lumen diameter (p= 0.004), external arterial diameter (p = 0.0046,) and lumen/wall thickness ratio (p= 0.003) were increased in diabetes+BoNTA-treated animals. This effect was not observed in control or in tobacco-exposed groups.CONCLUSIONS:Botulinum toxin A increased skin flap viability in control and diabetic rats on the seventh post-operative day. Increased lumen diameter, external arterial diameter, and lumen/wall thickness ratio were observed in the diabetes+BoNTA group. BoNTA had no effect in the tobacco-exposed group on the seventh postoperative day.
Assuntos
Animais , Humanos , Masculino , Toxinas Botulínicas Tipo A/farmacologia , Diabetes Mellitus Experimental/complicações , Fármacos Neuromusculares/farmacologia , Retalhos Cirúrgicos , Pele/efeitos dos fármacos , Poluição por Fumaça de Tabaco/efeitos adversos , Sobrevivência de Enxerto/efeitos dos fármacos , Necrose , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Estreptozocina , Pele/patologia , Retalhos Cirúrgicos/patologia , Fatores de TempoRESUMO
To investigate the effect of Botulinum toxin A (BoNTA) on skin flap viability in healthy, tobacco-exposed and diabetic rats. Ninety male Wistar rats (250-300g) were randomly divided into six groups: control+saline (C1), control+BoNTA (C2), tobacco-exposed+saline (T1), tobacco-exposed+BoNTA (T2) diabetes+saline (D1) and diabetes+BoNTA (D2). A dorsal cutaneous flap (3×10cm) was performed. Survival area and total area of the flaps were measured. Lumen diameter, external arterial diameter and lumen/wall thickness ratio were recorded. Survival area increased in control group with BoNTA injection compared with control animals injected with saline (C2 x C1; 0.9±0.1 vs0.67±0.15, p= 0.001). A similar result was found in diabetes group injected with BontA (D2 x D1; 0.97±0.2 vs0.61±0.24, p=0.018). No difference was observed in skin flap viability in tobacco-exposed groups (T2 x T1; 0.74±0.24 vs 0.64±0.21, p=0.871). Lumen diameter (p= 0.004), external arterial diameter (p = 0.0046,) and lumen/wall thickness ratio (p= 0.003) were increased in diabetes+BoNTA-treated animals. This effect was not observed in control or in tobacco-exposed groups. Botulinum toxin A increased skin flap viability in control and diabetic rats on the seventh post-operative day. Increased lumen diameter, external arterial diameter, and lumen/wall thickness ratio were observed in the diabetes+BoNTA group. BoNTA had no effect in the tobacco-exposed group on the seventh postoperative day.(AU)
Assuntos
Humanos , Animais , Masculino , Toxinas Botulínicas Tipo A/farmacologia , Diabetes Mellitus Experimental/complicações , Fármacos Neuromusculares/farmacologia , Pele , Retalhos Cirúrgicos , Poluição por Fumaça de Tabaco/efeitos adversos , Sobrevivência de Enxerto , Necrose , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Pele/patologia , Estreptozocina , Retalhos Cirúrgicos/patologia , Fatores de TempoRESUMO
BACKGROUND: Air pollution is associated with a substantial burden on human health; however, the most important pollutants may vary with location. Proper monitoring is necessary to determine the effect of these pollutants on respiratory health. OBJECTIVES: This study was designed to evaluate the role of outdoor, indoor and personal exposure to combustion-related pollutants NO(2) and O(3) on respiratory health of children in a non-affluent urban area of São Paulo, Brazil. METHODS: Levels of NO(2) and O(3) were continuously measured in outdoor and indoor air, as well as personal exposure, for 30 days using passive measurement monitors. Respiratory health was assessed with a Brazilian version of the ISAAC questionnaire. RESULTS: Complete data were available from 64 children, aged 6-10 years. Respiratory morbidity was high, with 43 (67.2%) reporting having had wheezing at any time, 27 (42.2%) wheezing in the last month, 17 (26.6%) asthma at any time and 21 (32.8%) pneumonia at any time. Correlations between levels of NO(2) and O(3) measured in the three locations evaluated were poor. Levels of NO(2) in indoor air and personal exposure to O(3) were independently associated with asthma (both cases P=.02), pneumonia (O(3), P=.02) and wheezing at any time (both cases P<.01). No associations were seen between outdoor NO(2) and O(3) and respiratory health. CONCLUSIONS: Exposure to higher levels of NO(2) and O(3) was associated with increased risk for asthma and pneumonia in children. Nonetheless, the place where the pollutants are measured influences the results. The measurements taken in indoor and personal exposure were the most accurate.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Asma/etiologia , Dióxido de Nitrogênio/efeitos adversos , Ozônio/efeitos adversos , Pneumonia/etiologia , Saúde da População Urbana , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/efeitos adversos , Asma/epidemiologia , Brasil/epidemiologia , Criança , Exposição Ambiental/efeitos adversos , Monitoramento Ambiental/instrumentação , Monitoramento Ambiental/métodos , Feminino , Filtração , Habitação , Humanos , Masculino , Dióxido de Nitrogênio/análise , Ozônio/análise , Pneumonia/epidemiologia , Áreas de Pobreza , Sons Respiratórios/etiologia , Fatores de Risco , Inquéritos e Questionários , Poluição por Fumaça de Tabaco/efeitos adversos , Emissões de Veículos/toxicidadeRESUMO
Clinical evidence has identified the pulmonary circulation as an important target of air pollution. It was previously demonstrated that in vitro exposure to fine particulate matter (aerodynamic diameter≤2.5 µm, PM2.5) induces endothelial dysfunction in isolated pulmonary arteries. We aimed to investigate the effects of in vivo exposure to urban concentrated PM2.5 on rat pulmonary artery reactivity and the mechanisms involved. For this, adult Wistar rats were exposed to 2 weeks of concentrated São Paulo city air PM2.5 at an accumulated daily dose of approximately 600 µg/m3. Pulmonary arteries isolated from PM2.5-exposed animals exhibited impaired endothelium-dependent relaxation to acetylcholine without significant changes in nitric oxide donor response compared to control rats. PM2.5 caused vascular oxidative stress and enhanced protein expression of Cu/Zn- and Mn-superoxide dismutase in the pulmonary artery. Protein expression of endothelial nitric oxide synthase (eNOS) was reduced, while tumor necrosis factor (TNF)-α was enhanced by PM2.5 inhalation in pulmonary artery. There was a significant positive correlation between eNOS expression and maximal relaxation response (Emax) to acetylcholine. A negative correlation was found between vascular TNF-α expression and Emax to acetylcholine. Plasma cytokine levels, blood cells count and coagulation parameters were similar between control and PM2.5-exposed rats. The present findings showed that in vivo daily exposure to concentrated urban PM2.5 could decrease endothelium-dependent relaxation and eNOS expression on pulmonary arteries associated with local high TNF-α level but not systemic pro-inflammatory factors. Taken together, the present results elucidate the mechanisms underlying the trigger of cardiopulmonary diseases induced by urban ambient levels of PM2.5.
Assuntos
Endotélio Vascular/efeitos dos fármacos , Inflamação/induzido quimicamente , Material Particulado/toxicidade , Artéria Pulmonar/efeitos dos fármacos , Animais , Endotélio Vascular/fisiologia , Masculino , Óxido Nítrico Sintase Tipo III/análise , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/análiseRESUMO
OBJECTIVE: The present study was designed to evaluate the effects of urban, traffic-related, fine particulate matter (PM2.5) on mice lung tumorigenesis under controlled exposure conditions. METHODS: Four groups of female Swiss mice were treated with intraperitonial injections of urethane and saline solution. Urethane was used to start the carcinogenesis process. The animals were housed in two chambers receiving filtered and polluted air. In the polluted air chamber, pollutant levels were low. After two months of exposure, the animals were euthanized and lung tumoral nodules were counted. RESULTS: Saline-treated animals showed no nodules. Urethane-treated animals showed 2.0+2.0 and 4.0+3.0 nodules respectively, in the filtered and non-filtered chambers (p = 0.02), thus showing experimental evidence of increased carcinogenic-induced lung cancer with increasing PM2.5 exposure. CONCLUSION: Our data support the concept that low levels of PM2.5 may increase the risk of developing lung tumors.
Assuntos
Poluentes Atmosféricos/toxicidade , Neoplasias Pulmonares/induzido quimicamente , Animais , Carcinógenos , Transformação Celular Neoplásica/patologia , Modelos Animais de Doenças , Exposição Ambiental/efeitos adversos , Feminino , Neoplasias Pulmonares/patologia , Camundongos , Material Particulado/efeitos adversos , Material Particulado/análise , Material Particulado/toxicidade , Distribuição Aleatória , Fatores de Risco , Fatores de Tempo , UretanaRESUMO
OBJECTIVE: The present study was designed to evaluate the effects of urban, traffic-related, fine particulate matter (PM2.5) on mice lung tumorigenesis under controlled exposure conditions. METHODS: Four groups of female Swiss mice were treated with intraperitonial injections of urethane and saline solution. Urethane was used to start the carcinogenesis process. The animals were housed in two chambers receiving filtered and polluted air. In the polluted air chamber, pollutant levels were low. After two months of exposure, the animals were euthanized and lung tumoral nodules were counted. RESULTS: Saline-treated animals showed no nodules. Urethane-treated animals showed 2.0+2.0 and 4.0+3.0 nodules respectively, in the filtered and non-filtered chambers (p = 0.02), thus showing experimental evidence of increased carcinogenic-induced lung cancer with increasing PM2.5 exposure. CONCLUSION: Our data support the concept that low levels of PM2.5 may increase the risk of developing lung tumors.