Sílica e tabagismo: associação na produção de dano pulmonar / Silica dust and tobacco smoking: association in lung damage

Introdução: A relação entre a sílica e o tabaco como potencializadores na geração de fibrose pulmonar não foi ainda bem estabelecida, embora tenham sido postulados alguns mecanismos fisiopatológicos para embasá-la. É necessário reconhecer o papel das diversas células envolvidas na resposta inflamatória, assim como as diversas vias biológicas que participam na gênese. Esses fatores nos motivaram a desenvolver a presente revisão descritiva. Resultados: Cada vez mais evidências sugerem que a inflamação local produzida por exposição à sílica e à fumaça do tabaco pode ser modulada por fatores genéticos, mecanismos epigenéticos, reações autoimunes e hipóxia local, levando à transição epitélio-mesênquima e ao acúmulo de material necrótico no pulmão, o que contribui à perpetuação da inflamação e a uma resposta imunológica inata exagerada nos trabalhadores com silicose fumantes. Conclusão: Comparações diretas de diferentes estudos de mensuração de biomarcadores inflamatórios associados à silicose e ao tabagismo devem ser realizadas com cautela, devido a uma série de possíveis fatores de confusão, como compartimentalização ou interação com as diversas vias biológicas e tipos celulares envolvidos. Convém destacar que para se evitar a ocorrência de dano pulmonar nos trabalhadores expostos à sílica, devem-se melhorar os sistemas de ventilação e reduzir sua exposição. No contexto da cessação do tabagismo, é necessário o uso de componentes psicoterapêuticos, com o fim de evitar o dano pulmonar precocemente

Background: The relationship between silica dust and tobacco smoking as enhancers of pulmonary fibrosis development has not yet been well established. Some pathophysiological mechanisms which might support this relationship were postulated. The role of different cells involved in the inflammatory response, and of different biological pathways needs to be recognized. These facts encouraged us to perform the present descriptive review. Results: Growing evidence suggests that local inflammation induced by exposure to silica dust and tobacco smoking might be modulated by genetic factors, epigenetic mechanisms, autoimmune reactions and local hypoxia, giving rise to the epithelial­mesenchymal transition. These phenomena lead to accumulation of necrotic material in the lungs, which contributes to inflammation's perpetuation and to an exaggerated innate immunological response among workers with silicosis who smoke. Conclusion: Direct comparisons of different measurement studies of inflammatory biomarkers associated with silicosis and tobacco smoking should be performed cautiously due to several possible confounding factors, such as compartmentalization or interaction among the various biological pathways and cell types involved. Ventilation systems should be improved and exposure reduced to prevent lung damage in workers exposed to silica. In regard to smoking cessation, psychotherapy approaches are needed for early prevention of lung damage

Protective roles of pulmonary rehabilitation mixture in experimental pulmonary fibrosis in vitro and in vivo

Abnormal high mobility group protein B1 (HMGB1) activation is involved in the pathogenesis of pulmonary fibrosis. Pulmonary rehabilitation mixture (PRM), which combines extracts from eight traditional Chinese medicines, has very good lung protection in clinical use. However, it is not known if PRM has anti-fibrotic activity. In this study, we investigated the effects of PRM on transforming growth factor-β1 (TGF-β1)-mediated and bleomycin (BLM)-induced pulmonary fibrosis in vitro and in vivo. The effects of PRM on TGF-β1-mediated epithelial-mesenchymal transition (EMT) in A549 cells, on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on BLM-induced pulmonary fibrosis in vivo were investigated. PRM treatment resulted in a reduction of EMT in A549 cells that was associated with attenuating an increase of vimentin and a decrease of E-cadherin. PRM inhibited the proliferation of HLF-1 at an IC50 of 0.51 µg/mL. PRM ameliorated BLM-induced pulmonary fibrosis in rats, with reduction of histopathological scores and collagen deposition, and a decrease in α-smooth muscle actin (α-SMA) and HMGB1 expression. An increase in receptor for advanced glycation end-product (RAGE) expression was found in BLM-instilled lungs. PRM significantly decreased EMT and prevented pulmonary fibrosis through decreasing HMGB1 and regulating RAGE in vitro and in vivo. PRM inhibited TGF-β1-induced EMT via decreased HMGB1 and vimentin and increased RAGE and E-cadherin levels. In summary, PRM prevented experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.

effects of taurochenodeoxycholic acid in preventing pulmonary fibrosis in mice

The present study prepared the pulmonary fibrosis model in mice by using Bleomycin and carry out the investigations on the effects of taurochenodeoxycholic acid [TCDCA] in preventing pulmonary fibrosis in mice. Expression profiles of the bile acid receptors in the lung of mice FXRalpha and TGR5 were examined, and pulmonary coefficient, pathohistology as well as expression of TNF-alpha, MMP-2, MMP-9 and TIMP-2 in pulmonary fibrosis mice. The results showed that FXRalpha and TGR5 simultaneously expressed in the lung of the mice; TCDCA in dosages of 0.05 and 0.1g/kg can extremely significantly decrease the pulmonary coefficient in the model mice [P<0.01], TCDCA in a dosage of 0.2g/kg significantly decreased the pulmonary coefficient in the model mice [P<0.05]; TCDCA in dosages of 0.05 and 0.1g/kg significantly reduce the pathological damages on their lungs; TCDCA can extremely significantly decrease the expression levels of TNF-alpha and TIMP-2 in pulmonary tissues in the pulmonary fibrosis mice [P<0.01], the expression level of MMP-9 extremely significantly increased [P<0.01], while it has no significant effects on MMP2. The results as mentioned above indicated that TCDCA had antagonistic actions on pulmonary fibrosis in mice

Efeitos da quercetina na lesão pulmonar induzida por bleomicina: um estudo preliminar / Effects of quercetin on bleomycin-induced lung injury: a preliminary study

OBJETIVO: Investigar os efeitos da quercetina em um modelo de inflamação pulmonar e fibrose induzidas por bleomicina. MÉTODOS: Setenta e nove hamsters machos adultos foram randomizados para aplicação de injeções pelas vias intratraqueal (IT) e intraperitoneal (IP) em quatro configurações: veículo IP/salina IT (grupo VS, n = 16); salina IT/quercetina IP (grupo QS, n = 16); bleomicina IT/veículo IP (grupo VB, n = 27); e bleomicina IT/quercetina IP (grupo QB, n = 20). A quercetina e a bleomicina foram aplicadas em doses de 30 mg/kg/dia e 10 U/kg, respectivamente.A quercetina foi iniciada/suspensa 3 dias antes/14 dias depois das injeções IT. RESULTADOS: A taxa de mortalidade do grupo VB foi significantemente superior à dos demais grupos (44 por cento vs. VS: 0 por cento; QS: 0 por cento; QB: 15 por cento). O grupo VB exibiu níveis pulmonares de substâncias reativas ao ácido tiobarbitúrico (× 10-2 nmol/mg) significativamente maiores (6,6 ± 1,3 vs. VS: 5,5 ± 0,8; QS: 2,5 ± 0,6; e QB: 5,8 ± 0,6).Os grupos VB/QB mostraram níveis pulmonares de glutationa reduzida (× 10-2 nmol/mg) significativamente menores que os dos grupos VS/QS (28,9 ± 13,8/28,6 ± 14,8 vs. 43,9 ± 16,0/51,1 ± 20,3) e níveis de hidroxiprolina (mg/g) significativamente maiores (201,6 ± 37,3/177,6 ± 20,3 vs. 109,6 ± 26,1/117,5 ± 32,0). CONCLUSÕES: Em um modelo animal de lesão pulmonar, a quercetina exibiu efeitos antiinflamatórios que são relacionados, pelo menos em parte, a suas propriedades antioxidantes.

OBJECTIVE: The aim of this study was to identify the best experimental model in which to observe the pulmonary alterations characterizing hepatopulmonary syndrome (HPS). METHODS: Male Wistar rats, with mean weight of 250 g, were used in four experimental models: inhaled carbon tetrachloride; intraperitoneal carbon tetrachloride; partial portal vein ligation; and bile duct ligation (BDL). The animals in all groups were divided into control and experimental subgroups. The following variables were measured: transaminase levels; blood gases; lipoperoxidation, using thiobarbituric acid reactive substances (TBARS) and chemiluminescence; and levels of superoxide dismutase (SOD) anti-oxidant activity. Anatomopathological examination of the lung was also performed. RESULTS: There were statistically significant differences between the BDL control and BDL experimental groups: aspartate aminotransferase (105.3 ± 43 vs. 500.5 ± 90.3 IU/L); alanine aminotransferase (78.75 ± 37.7 vs. 162.75 ± 35.4 IU/L); alkaline phosphatase (160 ± 20.45 vs. 373.25 ± 45.44 IU/L); arterial oxygen tension (85.25 ± 8.1 vs. 49.9 ± 22.5 mmHg); and oxygen saturation (95 ± 0.7 vs. 73.3 ± 12.07 percent). Lipoperoxidation and antioxidant activity also differed significantly between the two BDL groups (control vs. experimental): TBARS (0.87 ± 0.3 vs. 2.01 ± 0.9 nmol/mg protein); chemiluminescence (16008.41 ± 1171.45 vs. 20250.36 ± 827.82 cps/mg protein); and SOD (6.66 ± 1.34 vs. 16.06 ± 2.67 IU/mg protein). The anatomopathological examination confirmed pulmonary vasodilatation in the BDL model. In the other models, there were no alterations that were characteristic of HPS. CONCLUSIONS: The data obtained suggest that the BDL model can be used in future studies involving hepatic alterations related to oxidative stress and HPS.

Doença intesticial pulmonar nas colagenoses / Interstitial lung disease in the collagenoses

Os autores revisam o acometimento pulmonar nas doenças do tecido conectivo, em especial a doença intersticial. Esta forma de acometimento tem implicaçöes terapêuticas e prognósticas sobretudo nas colagenoses clássicas (doença reumatóide, lúpus eritematoso sistêmico, esclerose sistêmica progressiva, polidermatomiosite, síndrome de Sjögren e doença mista do tecido conectivo). Säo apresentados os métodos empregados na investigaçäo destes pacientes, que incluem, além da história e do exame físico, avaliaçäo radiológica (incluindo a tomografia computadorizada de alta resoluçäo) e funcional (com medidas dos volumes, capacidades, fluxos, difusäo e gases sanguíneos), realizaçäo da cintilografia pulmonar com citrato de gálio-67, análise da celularidade do trato respieratório baixo por meio do lavado broncoalveolar e, finalmente, estudo histológico dos pulmöes. Discutem principalmente o valor do mapeamento con=m gálio-67 e do lavado broncoalveolar na compreensäo da patogênese e no diagnóstico precoce destes processos, aventando as suas possíveis implicaçöes terapêuticas