RESUMO
Air pollution caused by fuel burning contributes to respiratory impairments that may lead to death. We aimed to investigate the effects of biodiesel (DB) burning in mouse lungs. DB particulate matter was collected from the exhaust pipes of a bus engine. Mice were treated with 250 µg or 1000 µg of DB particulate matter by intranasal instillation over 5 consecutive days. We demonstrated that DB particulate matter penetrated the lung in the 250-µg and 1000-µg groups. In addition, the DB particulate matter number in pulmonary parenchyma was 175-fold higher in the 250-µg group and 300-fold higher in the 1000-µg group compared to control mice. The instillation of DB particulate matter increased the macrophage number and protein levels of TNF-alpha in murine lungs. DB particulate matter enhanced ROS production in both exposed groups and the malondialdehyde levels compared to the control group. The protein expression levels of Nrf2, p-NF-kB, and HO-1 were higher in the 250-µg group and lower in the 1000-µg group than in control mice and the 250-µg group. In conclusion, DB particulate matter instillation promotes oxidative stress by activating the Nrf2/HO-1 and inflammation by p-NF-kB/TNF-alpha pathways.
Assuntos
Exposição Ambiental/efeitos adversos , Pulmão/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/efeitos adversos , Emissões de Veículos/toxicidade , Animais , Heme Oxigenase-1/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Proteínas de Membrana/metabolismo , Redes e Vias Metabólicas , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Material Particulado/toxicidade , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Microcystin-LR (MC-LR) can cause serious injuries upon short- and long-term exposures that can be prevented by LASSBio-596 (LB-596), an anti-inflammatory compound. We aimed to test LB-596 following subchronic exposure to MC-LR. Swiss mice received 10 intraperitoneal injections of distilled water (DW) or MC-LR (20 µg/kg bw) every 2 days. On the 10th injection animals receiving DW were gavaged with DW or 50 mg/kg bw of LB-596 for 1 or 7 days (C1D, C7D, CL1D and CL7D groups), whereas those exposed to MC-LR received either DW or 50 mg/kg of LB-596 for 1 or 7 days (T1D, T7D, TL1D and TL7D groups). Twelve hours after the last gavage we assessed respiratory mechanics, and extracted lung and liver for histology, apoptosis, inflammatory biomarkers and MC-LR content. C1D, C7D, CL1D and CL7D were all similar. Mechanical parameters were significantly higher in T1D and T7D compared to the other groups. LB-596 reversed these changes on day 1 of administration. LB-596 reduced inflammatory mediators in lung and liver on day 1 of treatment. On day 7 apoptosis in liver and lung fell even more. Briefly, 7-day administration completely reversed lung and liver changes.
Assuntos
Anti-Inflamatórios/administração & dosagem , Fígado/patologia , Pulmão/patologia , Microcistinas/antagonistas & inibidores , Ácidos Ftálicos/administração & dosagem , Sulfonamidas/administração & dosagem , Administração Oral , Animais , Anti-Inflamatórios/uso terapêutico , Apoptose/efeitos dos fármacos , Inflamação , Fígado/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Masculino , Toxinas Marinhas , Camundongos , Microcistinas/análise , Microcistinas/toxicidade , Ácidos Ftálicos/uso terapêutico , Mecânica Respiratória/efeitos dos fármacos , Sulfonamidas/uso terapêutico , Fatores de TempoRESUMO
BACKGROUND: There are no studies examining the effects of sevoflurane on a chronically inflamed and remodeled airway, such as that found in asthma. In the present study, we sought to define the respiratory effects of sevoflurane in a model of chronic allergic asthma. For this purpose, pulmonary mechanics were studied and lung morphometry analyzed to determine whether the physiological modifications reflected underlying morphological changes. METHODS: Thirty-six BALB/c mice (20-25 g) were randomly divided into four groups. In OVA groups, mice were sensitized with ovalbumin and exposed to repeated ovalbumin challenges. In SAL groups, mice received saline using the same protocol. Twenty-four hours after the last challenge, the animals were anesthetized with pentobarbital sodium (PENTO, 20 mg/kg i.p.) or sevoflurane (SEVO, 1 MAC). Lung static elastance (Est), resistive ([DELTA]P1) and viscoelastic/inhomogeneous ([DELTA]P2) pressure decreases were analyzed by an end-inflation occlusion method. Lungs were fixed and stained for histological analysis. RESULTS: Animals in the OVASEVO group showed lower [DELTA]P1 (38%), [DELTA]P2 (24%), and Est (22%) than animals in the OVAPENTO group. Histology demonstrated greater airway dilation (16%) and a lower degree of alveolar collapse (25%) in the OVASEVO compared with OVAPENTO group. [DELTA]P1 was lower (35%) and airway diameters larger (12%) in the SALSEVO compared with SALPENTO group. CONCLUSION: Sevoflurane anesthesia acted both at airway level and lung periphery reducing ([DELTA]P1 and [DELTA]P2 pressures, and Est in chronic allergic asthma.
Assuntos
Anestésicos Inalatórios/farmacologia , Asma/tratamento farmacológico , Hipersensibilidade/tratamento farmacológico , Pulmão/efeitos dos fármacos , Éteres Metílicos/farmacologia , Animais , Modelos Animais de Doenças , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/farmacologia , Pressão , Respiração/efeitos dos fármacos , Mecânica Respiratória/efeitos dos fármacos , Sevoflurano , Fatores de TempoRESUMO
Cigarette smoke (CS) induces pulmonary emphysema by inflammation, oxidative stress, and metalloproteinase (MMP) activation. Pharmacological research studies have not focused on tissue repair after the establishment of emphysema but have instead focused on inflammatory stimulation. The aim of our study was to analyze the effects of atorvastatin and simvastatin on mouse lung repair after emphysema caused by CS. Male mice (C57BL/6, n = 45) were divided into the following groups: control (sham-exposed), CSr (mice exposed to 12 cigarettes a day for 60 days and then treated for another 60 days with the vehicle), CSr+A (CSr mice treated with atorvastatin for 60 days), and CSr+S (CSr mice treated with simvastatin for 60 days). The treatment with atorvastatin and simvastatin was administered via inhalation (15 min with 1 mg/mL once a day). Mice were sacrificed 24 h after the completion of the 120-day experimental procedure. We performed biochemical, morphological, and physiological analyses. We observed decreased levels of leukocytes and cytokines in statin-treated mice, accompanied by a reduction in oxidative stress markers. We also observed a morphological improvement confirmed by a mean linear intercept counting in statin-treated mice. Finally, statins also ameliorated lung function. We conclude that inhaled atorvastatin and simvastatin improved lung repair after cigarette smoke-induced emphysema in mice.
Assuntos
Atorvastatina/farmacologia , Pulmão/efeitos dos fármacos , Enfisema Pulmonar/tratamento farmacológico , Sinvastatina/farmacologia , Animais , Atorvastatina/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Enfisema Pulmonar/etiologia , Sinvastatina/uso terapêutico , Fumar/efeitos adversosRESUMO
We had previously shown that microcystin-LR (MCLR) could induce lung and liver inflammation after acute exposure. The biological outcomes following prolonged exposure to MCLR, although more frequent, are still poorly understood. Thus, we aimed to verify whether repeated doses of MCLR could damage lung and liver and evaluate the dose-dependence of the results. Male Swiss mice received 10 intraperitoneal injections (i.p.) of distilled water (60 µL, CTRL) or different doses of MCLR (5 µg/kg, TOX5), 10 µg/kg (TOX10), 15 µg/kg (TOX15) and 20 µg/kg (TOX20) every other day. On the tenth injection respiratory mechanics (lung resistive and viscoelastic/inhomogeneous pressures, static elastance, and viscoelastic component of elastance) was measured. Lungs and liver were prepared for histology (morphometry and cellularity) and inflammatory mediators (KC and MIP-2) determination. All mechanical parameters and alveolar collapse were significantly higher in TOX5, 10, 15 and 20 than CTRL, but did not differ among them. Lung inflammatory cell content increased dose-dependently in all TOX groups in relation to CTRL, being TOX20 the largest. The production of KC was increased in lung and liver homogenates. MIP-2 increased in the liver of all TOX groups, but in lung homogenates it was significantly higher only in TOX20 group. All TOX mice livers showed steatosis, necrosis, inflammatory foci and a high degree of binucleated hepatocytes. In conclusion, sub-chronic exposure to MCLR damaged lung and liver in all doses, with a more important lung inflammation in TOX20 group.
Assuntos
Toxinas Bacterianas/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Fígado/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Toxinas Marinhas/toxicidade , Microcistinas/toxicidade , Pneumonia/induzido quimicamente , Animais , Toxinas Bacterianas/administração & dosagem , Toxinas Bacterianas/isolamento & purificação , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Quimiocina CXCL2/agonistas , Quimiocina CXCL2/metabolismo , Quimiocinas/agonistas , Quimiocinas/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/toxicidade , Hepatite/etiologia , Injeções Intraperitoneais , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Toxinas Marinhas/administração & dosagem , Toxinas Marinhas/isolamento & purificação , Camundongos , Microcistinas/administração & dosagem , Microcistinas/isolamento & purificação , Microcystis/química , Tamanho do Órgão/efeitos dos fármacos , Fosfoproteínas Fosfatases/antagonistas & inibidores , Pneumonia/metabolismo , Pneumonia/patologia , Distribuição Aleatória , Testes de Toxicidade SubcrônicaRESUMO
The cyanotoxin cylindrospermopsin (CYN) has lately been reported with a notorious toxicity to mammals. LASSBio-596 is a compound with anti-inflammatory actions. We aimed at evaluating the therapeutic effects of LASSBio-596 in a model of CYN-induced lung injury. Protocol #1: BALB/c mice received intratracheally (i.t.) 50-µL of saline or semi-purified extract of CYN (70 µg/kg). 18 h later, animals that received saline were gavaged with saline (SALSAL) or 50 mg/kg of LASSBio-596 (SALLAS), and mice that received CYN were gavaged with either saline (TOXSAL) or 50 mg/kg of LASSBio-596 (TOXLAS). Pulmonary mechanics was measured 6 h after gavage. Lungs were prepared for histology and inflammatory mediators determination. Protocol #2: Mice received 50-µL of CYN (70 µg/kg, i.t.) and 18 h later were gavaged with saline (NOT TREATED), or 50 mg/kg of LASSBio-596 (TREATED). Survival rates and pulmonary mechanics of the survivors were assessed. CYN exposure increased mechanical components, alveolar collapse, PMN cells and fiber deposition in the lungs, as well as the production of IL-1ß, IL-6 and KC in Protocol #1. LASSBio-596 attenuated those changes. TREATED mice in Protocol #2 presented significantly higher survival rates and tended to improve lung mechanics. Briefly, LASSBio-596 showed positive effects in mice exposed to CYN.
Assuntos
Anti-Inflamatórios/uso terapêutico , Lesão Pulmonar/tratamento farmacológico , Ácidos Ftálicos/uso terapêutico , Sulfonamidas/uso terapêutico , Uracila/análogos & derivados , Alcaloides , Animais , Anti-Inflamatórios/efeitos adversos , Toxinas Bacterianas , Toxinas de Cianobactérias , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/patologia , Camundongos Endogâmicos BALB C , Ácidos Ftálicos/efeitos adversos , Sulfonamidas/efeitos adversos , Análise de Sobrevida , Uracila/toxicidadeRESUMO
Residual oil fly ash (ROFA) is a common pollutant in areas where oil is burned. This particulate matter (PM) with a broad distribution of particle diameters can be inhaled by human beings and putatively damage their respiratory system. Although some studies deal with cultured cells, animals, and even epidemiological issues, so far a comprehensive analysis of respiratory outcomes as a function of the time elapsed after exposure to a low dose of ROFA is wanted. Thus, we aimed to investigate the time course of mechanical, histological, and inflammatory lung changes, as well as neutrophils in the blood, in mice exposed to ROFA until 5 days after exposure. BALB/c mice (25 ± 5 g) were randomly divided into 7 groups and intranasally instilled with either 10 µL of sterile saline solution (0.9% NaCl, CTRL) or ROFA (0.2 µg in 10 µL of saline solution). Pulmonary mechanics, histology (normal and collapsed alveoli, mononuclear and polymorphonuclear cells, and ultrastructure), neutrophils (in blood and bronchoalveolar lavage fluid) were determined at 6 h in CTRL and at 6, 24, 48, 72, 96, and 120 h after ROFA exposure. ROFA contained metal elements, especially iron, polycyclic aromatic hydrocarbons (PAHs), and organochlorines. Lung resistive pressure augmented early (6 h) in the course of lung injury and other mechanical, histological and inflammatory parameters increased at 24 h, returning to control values at 120 h. Blood neutrophilia was present only at 24 and 48 h after exposure. Swelling of endothelial cells with adherent neutrophils was detected after ROFA instillation. No neutrophils were present in the lavage fluid. In conclusion, the exposure to ROFA, even in low doses, induced early changes in pulmonary mechanics, lung histology and accumulation of neutrophils in blood of mice that lasted for 4 days and disappeared spontaneously.
RESUMO
Rats exposed to the quaternary herbicide paraquat (PQ) exhibit oxidative stress and lung injury. In the present study, we investigated the effect of multiple exposures to PQ on aerobic performance during progressive exercise on a treadmill in rats. PQ was dissolved in saline (SAL) (10 mg/ml) and administered intraperitoneally 7 mg/kg body wt to Wistar rats (n = 5) once a week for one month. Control rats received SAL (0.7 ml/kg body wt., intraperitoneally, n = 5) over the same time period. The animals were submitted to aerobic evaluation on a treadmill using a progressive protocol until fatigue prior to the administration of the first dose of PQ or SAL and repeated at 1 week and 40 days following the last dose of the herbicide. Twenty-four hours after the last performance tests, the animals were sacrificed, lungs removed and divided in two groups: PQ and SAL for histopathological analysis. The animals exposed to PQ exhibited decrease in aerobic performance and mechanical efficiency (ME) as well as increase in oxygen consumption during exercise in comparison to the controls forty days after the last dose of PQ. Lung histologic changes included atelectasis, interstitial edema, and inflammation cells in PQ group. The collagen system fibers, fraction area of alveolar collapse and influx of polymorphonuclear (PMN) cells in lung parenchyma were higher in PQ compared to SAL. In conclusion, multiple exposures to PQ induce pulmonary fibrosis, reduce the aerobic performance and mechanical efficiency and increase the metabolic cost of exercise in rats.