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2.
Rev Med Suisse ; 16(698): 1256-1260, 2020 Jun 17.
Artigo em Francês | MEDLINE | ID: mdl-32558455

RESUMO

A significant proportion - up to 40 % - of patients suffering from fibrosing interstitial pneumonia will acquire a progressive phenotype which shares genetic and pathogenic mechanisms, as well a clinical behavior similar to those of idiopathic pulmonary fibrosis (IPF). It therefore makes sense to suggest that molecules with antifibrotic properties such as pirfenidone and nintedanib could be effective in patients with progressive fibrosing interstitial lung disease as they are in patients with IPF. The first studies published on this topic show encouraging results which however have to be confirmed on a larger scale.


Assuntos
Fibrose Pulmonar/tratamento farmacológico , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/patologia , Indóis/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/patologia , Fibrose Pulmonar/patologia , Piridonas/uso terapêutico
3.
Zhongguo Zhong Yao Za Zhi ; 45(7): 1481-1487, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32489024

RESUMO

Since February 2020, a large number of patients infected with new coronavirus has been cured and discharged with the controlling of epidemic. Pulmonary fibrosis, which may be one of the sequela caused by COVID-19, not only brings dyspnea and deterioration of lung function, but also affects patients' life because of its high mortality and poor prognosis. Vascular endothelial growth factor receptor(VEGFR) and fibroblast growth factor receptor(FGFR) can inhibit the proliferation, activation and migration of fibroblasts by regulating the signal transduction pathway involved in the process of pulmonary fibrosis. Chinese herbal formulas pose a good therapeutic effect on pulmonary fibrosis. Present study explores the intervention effect on pulmonary fibrosis of traditional Chinese medicine(TCM) by screening the potential inhibitors of VEGFR and FGFR. The docking models of VEGFR and FGFR were established to obtain the potential active ingredients which were filtered by the docking score. According to 2 prescriptions in the Protocol for the diagnosis and treatment of coronavirus disease 2019(7th edition)and 9 prescriptions in Traditional Chinese medicine prescriptions for treating blight, 959 and 1 047 potential ingredients were obtained as the inhibitors of VEGFR and FGFR respectively with the screening thres-hold set as eighty percent of the docking score of the initial ligands. The potential herbs were then filtered by the components with a hit rate higher than 30%, such as Scutellariae Radix, Adenophorae Radix, Pinelliae Rhizoma, Coicis Semen, etc. To discuss the rule of TCM in the treatment of pulmonary fibrosis, the networks of TCM-channel tropism and TCM-efficacy of the potential herbs was constructed. The potential herbs for treating pulmonary fibrosis mostly belong to lung(degree=14) and spleen(degree value=8), and the efficacy is focused on reinforcing deficiency(degree=9). Qiyin Prescription and Buzhong Yiqi Decoction contain the largest number of the potential herbs. The main symptom of COVID-19 is damp-heat stagnating in the lung, which always causes impairment of body fluid and Qi. Clinical observation shows that patients in the recovery period are mostly at the status that the remaining virus toxicity is not exhausted while the vital Qi have not recovered. The results of this study are expected to provide references for clinical medication in preventing and treating pulmonary fibrosis caused by COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Medicamentos de Ervas Chinesas , Pandemias , Pneumonia Viral , Fibrose Pulmonar , Humanos , Medicina Tradicional Chinesa , Fibrose Pulmonar/tratamento farmacológico , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Receptores de Fatores de Crescimento do Endotélio Vascular
4.
Infez Med ; 28(suppl 1): 52-56, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32532939

RESUMO

In spite of many ongoing attempts to repurpose existing antivirals, no drugs have emerged yet with the desirable activity against SARS-CoV-2. Hydroxychloroquine, lopinavir/ritonavir, remdesivir, umifenovir, favipiravir, ribavirin and beta-interferon-1 gave rise to variable but still inconsistent proof of clinical efficacy in the treatment of COVID-19. Pathogenetic studies have shown significant differences between commonly defined viral pneumonia and COVID-19 pulmonary disease. In severe forms, immune/inflammatory alterations reminiscent of disease forms like Macrophage Activation Syndrome (MAS) have been described, and therapeutic options other than anti-infective have been proposed and implemented, such as anti-inflammatory and anticoagulative agents. The thrombotic phenomena described in the pulmonary vascular bed of patients with severe COVID-19 suggest the administration of low-molecular weight heparin (LMWH) as standard measure in hospitalized patients with COVID-19.


Assuntos
Anticoagulantes/uso terapêutico , Infecções por Coronavirus/complicações , Cuidados Críticos/métodos , Heparina de Baixo Peso Molecular/uso terapêutico , Pneumonia Viral/complicações , Trombofilia/tratamento farmacológico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Anticoagulantes/administração & dosagem , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Biomarcadores , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Gerenciamento Clínico , Método Duplo-Cego , Combinação de Medicamentos , Quimioterapia Combinada , Embolia/epidemiologia , Embolia/prevenção & controle , Endotélio Vascular/fisiopatologia , Heparina de Baixo Peso Molecular/administração & dosagem , Humanos , Hidroxicloroquina/uso terapêutico , Interferon beta-1b/uso terapêutico , Lopinavir/uso terapêutico , Ativação de Macrófagos , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/fisiopatologia , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Ritonavir/uso terapêutico , Tromboembolia/epidemiologia , Tromboembolia/prevenção & controle , Trombofilia/sangue , Trombofilia/etiologia , Trombose/epidemiologia , Trombose/prevenção & controle
5.
Korean J Radiol ; 21(6): 746-755, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32410413

RESUMO

OBJECTIVE: To identify predictors of pulmonary fibrosis development by combining follow-up thin-section CT findings and clinical features in patients discharged after treatment for COVID-19. MATERIALS AND METHODS: This retrospective study involved 32 confirmed COVID-19 patients who were divided into two groups according to the evidence of fibrosis on their latest follow-up CT imaging. Clinical data and CT imaging features of all the patients in different stages were collected and analyzed for comparison. RESULTS: The latest follow-up CT imaging showed fibrosis in 14 patients (male, 12; female, 2) and no fibrosis in 18 patients (male, 10; female, 8). Compared with the non-fibrosis group, the fibrosis group was older (median age: 54.0 years vs. 37.0 years, p = 0.008), and the median levels of C-reactive protein (53.4 mg/L vs. 10.0 mg/L, p = 0.002) and interleukin-6 (79.7 pg/L vs. 11.2 pg/L, p = 0.04) were also higher. The fibrosis group had a longer-term of hospitalization (19.5 days vs. 10.0 days, p = 0.001), pulsed steroid therapy (11.0 days vs. 5.0 days, p < 0.001), and antiviral therapy (12.0 days vs. 6.5 days, p = 0.012). More patients on the worst-state CT scan had an irregular interface (59.4% vs. 34.4%, p = 0.045) and a parenchymal band (71.9% vs. 28.1%, p < 0.001). On initial CT imaging, the irregular interface (57.1%) and parenchymal band (50.0%) were more common in the fibrosis group. On the worst-state CT imaging, interstitial thickening (78.6%), air bronchogram (57.1%), irregular interface (85.7%), coarse reticular pattern (28.6%), parenchymal band (92.9%), and pleural effusion (42.9%) were more common in the fibrosis group. CONCLUSION: Fibrosis was more likely to develop in patients with severe clinical conditions, especially in patients with high inflammatory indicators. Interstitial thickening, irregular interface, coarse reticular pattern, and parenchymal band manifested in the process of the disease may be predictors of pulmonary fibrosis. Irregular interface and parenchymal band could predict the formation of pulmonary fibrosis early.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/virologia , Adulto , Idoso , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Feminino , Humanos , Masculino , Microtomia/métodos , Pessoa de Meia-Idade , Pandemias , Alta do Paciente , Derrame Pleural/patologia , Derrame Pleural/virologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Valor Preditivo dos Testes , Fibrose Pulmonar/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
6.
Eur Rev Med Pharmacol Sci ; 24(8): 4537-4538, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32373992

RESUMO

At present, SARS-Cov-2 is spread all over the world, becoming a serious threat to people's health. SARS-Cov-2 has a strong infection, and the mortality rate of severe patients after infection is high, but there is no effective treatment. Mesenchymal stem cells (MSCs) have anti-inflammatory and immunomodulatory functions, which can reduce the occurrence of cytokine storm syndrome and acute respiratory distress syndrome. At the same time, MSCs can reduce the level of pulmonary fibrosis and enhance tissue injury repair. In this short report, combined with the progress of preclinical and clinical research, we comment the efficacy of MSCs in the treatment of COVID-19.


Assuntos
Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais , Pneumonia Viral/terapia , Animais , Betacoronavirus , Citocinas/efeitos adversos , Citocinas/imunologia , Humanos , Imunomodulação , Pandemias , Fibrose Pulmonar/terapia , Síndrome do Desconforto Respiratório do Adulto/terapia
9.
Chin Med J (Engl) ; 133(12): 1390-1396, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32251003

RESUMO

BACKGROUND: Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients. METHODS: From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores. RESULTS: Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation. CONCLUSIONS: LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Transplante de Pulmão/métodos , Pneumonia Viral/complicações , Fibrose Pulmonar/cirurgia , Síndrome do Desconforto Respiratório do Adulto/cirurgia , Idoso , Infecções por Coronavirus/mortalidade , Oxigenação por Membrana Extracorpórea , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Fibrose Pulmonar/mortalidade , Síndrome do Desconforto Respiratório do Adulto/mortalidade
10.
Ecotoxicol Environ Saf ; 193: 110364, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32114243

RESUMO

Silicosis is a fatal fibrotic lung disease caused by long-term silica particle exposure, in which pulmonary macrophages play an important role. However, the relationship between macrophage polarization and silicosis remains unclear. We established an experimental silicosis mouse model to investigate macrophage polarization during silicosis development. C57BL/c mice were exposed to silica by intra-tracheal instillation and sacrificed at different time points. Lung tissues and bronchoalveolar lavage fluid were collected for flow cytometry, quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assays, western blotting, and histology examinations. The polarization of pulmonary macrophages was dysregulated during silicosis development. In the early stage of silicosis, M1 macrophages were induced and played a leading role in eliciting inflammatory; in the late stage, M2 macrophages were induced to promote tissue repair. Levels of several cytokines in lung tissue microenvironment changed with macrophage polarization. Inflammatory cytokines such as tumor necrosis factor-α and interleukin (IL)-1ß and IL-6 were upregulated in the inflammation stage, while the anti-inflammatory cytokine IL-10 was upregulated in the fibrosis stage. Furthermore, we found that STAT (signal transducer and activator of transcription) and IRF (interferon regulatory factor) signaling pathway were involved in the regulation of macrophage polarization in silicosis. In summary, macrophage polarization is closely related to the occurrence and development of silicosis and may be a key point for further elucidating silicosis pathogenesis.


Assuntos
Macrófagos Alveolares/efeitos dos fármacos , Silicose/imunologia , Animais , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Fatores Reguladores de Interferon/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/metabolismo , Fatores de Transcrição STAT/metabolismo , Dióxido de Silício , Silicose/metabolismo , Silicose/patologia
12.
Cancer Radiother ; 24(2): 120-127, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32173269

RESUMO

BACKGROUND: The main complication after hypofractionated radiotherapy for lung carcinoma is radiation-induced lung toxicity, which can be divided into radiation pneumonitis (acute toxicity, occurring within 6 months) and lung fibrosis (late toxicity, occurring after 6 months). The literature describes several predictive factors related to the patient, to the tumor (volume, central location), to the dosimetry and to biological factors. MATERIALS AND METHODS: This study is a retrospective analysis of 90 patients treated with stereotactic body irradiation for stage I non-small-cell lung carcinoma between December 2010 and May 2015. RESULTS: Radiation pneumonitis was observed in 61.5% of the patients who were mainly asymptomatic (34%). Chronic obstructive pulmonary disease was not predictive of radiation pneumonitis, whereas active smoking was protective. Centrally located tumors were not more likely to result in this complication if the radiation schedule utilized adapted fractionation. In our study, no predictive factor was identified. Whereas the mean lung dose was a predictive factor in 3D radiotherapy, the lung volume irradiated at high doses seemed to be involved in the pathogenesis after hypofractionated radiotherapy. CONCLUSION: The discovery of predictive factors for radiation pneumonitis is difficult due to the rarity of this complication, especially with an 8×7.5Gy schedule. Radiation pneumonitis seems to be correlated with the volume irradiated at high doses, which is in contrast to the known knowledge about the organs in parallel. This finding leads us to raise the hypothesis that vessel damage, organs in series, occurring during hypofractionated radiotherapy could be responsible for this toxicity.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Pulmão/efeitos da radiação , Pneumonite por Radiação/etiologia , Radiocirurgia/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Doença Pulmonar Obstrutiva Crônica/complicações , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/prevenção & controle , Pneumonite por Radiação/prevenção & controle , Radiocirurgia/métodos , Estudos Retrospectivos , Fumar
13.
Cell Physiol Biochem ; 54(2): 195-210, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32083406

RESUMO

BACKGROUND/AIMS: Idiopathic pulmonary fibrosis (IPF) is a specific form of progressive and chronic interstitial lung disease of unknown cause. IPF is characterized by excessive deposition of extracellular matrix (ECM) and destructive pathological remodeling due to epithelial-to-mesenchymal transition (EMT). Eventually, lung interstitium thickens and stiffens and breathing becomes difficult. It has been well established that the transforming growth factor-ß1 (TGF-ß1)/Smad signaling pathway plays a critical role in the pathogenesis of pulmonary fibrosis. TGF-ß1-mediated activation of mitogen activated protein kinase (MAPK) family affects Smad signaling. p90RSK is a serine/threonine kinase and is activated by the extracellular signal-regulated kinase (ERK) signaling pathway. However, the roles played by p90RSK in TGF-ß1 signaling and the pathogenesis of pulmonary fibrosis remain unknown. METHODS: We investigated whether p90RSK regulates the pathogenesis of pulmonary fibrosis using in vitro and in vivo systems and Western blotting, real-time quantitative PCR, transcriptional activity assays and immunofluorescence studies. RESULTS: Pharmacological inhibition of p90RSK by FMK or inhibition of p90RSK with adenoviral vector encoding a dominant negative form of p90RSK suppressed TGF-ß1-induced ECM accumulation and EMT in lung epithelial cells and fibroblasts. Interestingly, FMK significantly inhibited TGF-ß1-induced Smad3 nuclear translocation and smad binding element-dependent transcriptional activity, but not Smad3 phosphorylation. Furthermore, in a mouse model of bleomycin-induced lung fibrosis, FMK ameliorated pulmonary fibrosis. CONCLUSION: These findings indicate that p90RSK plays critical roles in pulmonary fibrosis, which suggests it be viewed as a novel therapeutic target for the treatment of lung fibrosis.


Assuntos
Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Proteína Smad3/metabolismo , Animais , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Matriz Extracelular/metabolismo , Humanos , Isoquinolinas/farmacologia , Cetonas/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Regiões Promotoras Genéticas/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Piridinas/farmacologia , Pirróis/farmacologia , Proteínas Quinases S6 Ribossômicas 90-kDa/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Proteína Smad3/antagonistas & inibidores , Proteína Smad3/genética , Ativação Transcricional/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo
14.
Chem Biol Interact ; 319: 109024, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32097614

RESUMO

Silicosis is an occupational pulmonary fibrosis that is caused by inhalation of silica (SiO2), and there are no effective drugs to treat this disease. Tanshinone IIA (Tan IIA), a natural product, has been reported to possess antioxidant and anti-fibrotic properties in various diseases. The purpose of the current study was to examine Tan IIA's protective effects against silica-induced pulmonary fibrosis and to explore the underlying mechanisms. We found that in vivo treatment with Tan IIA significantly relieved silica-induced lung fibrosis in a silicosis rat model by histological and immunohistochemical analyses. Further, in vitro mechanistic investigations, mainly using western blot and immunofluorescence analyses, revealed that Tan IIA administration markedly inhibited the silica-induced epithelial-mesenchymal transition (EMT) and transforming growth factor-ß1 (TGF-ß1)/Smad signaling pathway and also reduced silica-induced oxidative stress and activated the nuclear factor erythroid 2-related factor-2 (Nrf2) signaling pathway in A549 and human bronchial epithelial (HBE) cells. Furthermore, through transfection with siRNA, we demonstrate that Nrf2 activation partially mediates the suppression effects of Tan IIA on EMT and TGF-ß1/Smad signaling pathway activation induced by silica exposure, thus mediating the anti-fibrotic effects of Tan IIA against silica-induced pulmonary fibrosis. In our study, Tan IIA has been identified as a possible anti-oxidative and anti-fibrotic drug for silicosis.


Assuntos
Abietanos/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Células A549 , Animais , Antioxidantes/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Ratos , Ratos Sprague-Dawley , Dióxido de Silício/farmacologia
15.
Life Sci ; 246: 117423, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32057902

RESUMO

Bleomycin (BLM) is one of the most common anti-cancer drugs used to treat numerous types of tumors. However, pulmonary toxicity is considered the most dramatic effect of BLM. Therefore, BLM has been frequently used for induction of pulmonary fibrosis. This study aimed to evaluate the effect of nicorandil on BLM-induced pulmonary fibrosis and explore the possible mechanisms. BLM was instilled intratracheally into male Sprague-Dawley rats as a single dose (5 mg/kg) and oral nicorandil was given (30 mg/kg/day) for 6 weeks after BLM challenge. At the end of experimental period, rats were sacrificed, and lung histopathology and biochemical parameters were evaluated. Nicorandil therapy attenuated lung inflammation and fibrosis elicited by BLM. Nicorandil significantly reduced total protein content, lactate dehydrogenase (LDH) activity and total and differential cell counts. Moreover, nicorandil diminished lung levels of malondialdehyde and total nitrite/nitrate, in addition to increasing lung contents of reduced glutathione and superoxide dismutase activity. Nicorandil reduced lung and bronchoalveolar lavage fluid contents of hypoxia inducible factor-1α (HIF-1α) and lung content of thioredoxin-interacting protein (TXNIP). Besides, nicorandil significantly improved histological lesions and reduced collagen deposition as well as hydroxyproline content. Immunohistochemical examination revealed that nicorandil-treated rats exhibited significant diminutions in protein expression levels of transforming growth factor beta-1(TGF-ß1) and inducible nitric oxide synthase (iNOS) and enhanced pulmonary protein expression of endothelial NOS (eNOS). In conclusion, these results illustrate the possible potential effects of nicorandil for managing pulmonary fibrosis caused by BLM.


Assuntos
Antibióticos Antineoplásicos/toxicidade , Bleomicina/toxicidade , Proteínas de Ciclo Celular/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Nicorandil/farmacologia , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico/metabolismo , Fibrose Pulmonar/induzido quimicamente , Animais , Líquido da Lavagem Broncoalveolar/química , Proteínas de Ciclo Celular/análise , Subunidade alfa do Fator 1 Induzível por Hipóxia/análise , L-Lactato Desidrogenase/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Nicorandil/uso terapêutico , Nitratos/análise , Óxido Nítrico/análise , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Nitritos/análise , Fibrose Pulmonar/tratamento farmacológico , Ratos , Ratos Sprague-Dawley
16.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(2): 121-123, 2020 Feb 06.
Artigo em Chinês | MEDLINE | ID: mdl-32074695

RESUMO

This article summarized the use of guanidine disinfectants in China and the use of guanidine cationic disinfectants, polyhexamethylene guanidine (PHMG), in South Korea, which had caused severe lung damage events such as pulmonary fibrosis. The authors reviewed the studies that Chinese scientists employed ultrasonic atomization technology to simulate the actual scenario of human exposure to PHMG and proved the findings that PHMG could cause pulmonary fibrosis. These results could highlight the necessity of full attention to lung damage caused by guanidine disinfectants and its mechanism, so as to provide the important scientific basis for the protection of public health safety and the formulation of corresponding policies.


Assuntos
Desinfetantes/toxicidade , Guanidinas/toxicidade , Pneumopatias/induzido quimicamente , China , Humanos , Fibrose Pulmonar/induzido quimicamente , República da Coreia
17.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(2): 198-202, 2020 Feb 06.
Artigo em Chinês | MEDLINE | ID: mdl-32074710

RESUMO

Objective: To explore the lung damage caused by repeated inhalation of polyhexamethyleneguanidine (PHMG) disinfectant aerosol and the corresponding toxicological characteristics. Methods: Thirty four-week-old mice of C57BL/6N strain were randomly divided into three groups, the control group, low-dose group, and high-dose group. Each group had 5 male mice and 5 female mice. Lab II-level purified water was used in the control group. The PHMG disinfectant aerosol was generated by using the ultrasonic atomization of the aqueous solution containing PHMG. The PHMG concentrations in the low-and high-dose groups were 0.1 mg/ml (0.01%) and 1 mg/ml (0.1%), respectively. The concentration of PHMG in the post-chemical exposure room was 1.03 mg/m(3) and 9.09 mg/m(3) according to the air sampler analysis. The experimental mice were exposed to the PHMG in dynamic respiratory exposure mode for 4 hours every day in 21 days. After 21-day exposure, bronchia alveolus lung fluids (BALFs) were used to evaluate the inflammatory cells in the lungs, and pathological evaluation, special staining and immunohistochemical methods were further performed to evaluate the key indicators of pulmonary fibrosis. Results: Compared to the control group, the body weight of mice in the high-dose group was significantly decreased (P<0.05), while that of mice in the low-dose group did not significantly differ (P>0.05). The number of inflammatory cells in BALFs of low-dose exposed mice was slightly reduced, and the lung tissue pathology began to show lung damage with early fibrosis symptoms (P<0.05). The pathological examination of mice in the high-dose group showed changes in pulmonary fibrosis. Immunohistochemical staining showed that pulmonary fibrosis marker, α-SMA, was significantly increased in low-dose group and high-dose group (P<0.05). Conclusion: The repeated inhalation of PHMG disinfectant could cause lung damage such as pulmonary fibrosis in mice. It could suggest that special warnings should be given to this common disinfectant and respiratory protection measures should be adopted during industrial production and daily use.


Assuntos
Desinfetantes/toxicidade , Guanidinas/toxicidade , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Administração por Inalação , Animais , Desinfetantes/administração & dosagem , Feminino , Guanidinas/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória
18.
Toxicol Lett ; 323: 57-66, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32017981

RESUMO

Oxidative stress and inflammatory processes are proposed to mediate the development of silicosis. However, antioxidant therapy has not produced consistent results during the treatment of silicosis. α-Lipoic acid synthesized by lipoic acid synthase is a powerful anti-oxidant and helps protect mitochondria. Thus far, the effect of endogenous α-Lipoic acid on silicosis has not been elucidated yet. We established an experimental model of silicosis with wildtype and LiasH/H mice, a new antioxidant mouse model which has overexpressed Lias gene (∼150 %) relative to its wild type counterpart. We systemically examined main pathological changes of pulmonary fibrosis, and explored α-lipoic acid effects on oxidative stress, inflammatory and pulmonary fibrosis biomarkers in silica-instillated mice. In LiasH/H mice over-expression of lipoic acid alleviated the severity of major pathological alterations in the early stage of pulmonary fibrosis induced by silica compared with wild type mice. Silica significantly increased oxidative stress in both wild type and LiasH/H mice. The antioxidant defense was strengthen including increased NRF2 and LIAS production in LiasH/H mice. Relieved oxidative stress resulted in decreased inflammatory response and secretion of chemokines. LiasH/H mice reduced chronic inflammatory response and inhibition of NF-κB activity after silica instillation. The LiasH/H mouse model overexpression of lipoic acid synthase gene retarded the development of silica-induced pulmonary fibrosis. Strengthen antioxidant defense by increased lipoic acid synthase is a potential strategy for protection against silica-induced pulmonary fibrosis.


Assuntos
Fibrose Pulmonar/induzido quimicamente , Dióxido de Silício/toxicidade , Sulfurtransferases/fisiologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/fisiologia , NF-kappa B/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Fibrose Pulmonar/patologia , Fibrose Pulmonar/prevenção & controle , Fator de Crescimento Transformador beta1/fisiologia
19.
Mol Immunol ; 120: 83-92, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32106023

RESUMO

Pulmonary fibrosis is a progressive chronic inflammatory lung disease whose pathogenesis is complicated. Platelets and neutrophils play important roles in the progression of pulmonary inflammation. We have reported that cangrelor, a non-sepesific GPR17 antagonist, alleviates pulmonary fibrosis partly by inhibiting macrophage inflammation in mice. Cangrelor is also a well-known anti-platelet agent. To test whether cangrelor mitigated pulmonary fibrosis partly through the inhibition of platelets, bleomycin (BLM) was used to induce pulmonary fibrosis in C57BL/6 J mice. We found that cangrelor (10 mg/kg) not only significantly decreased BLM-induced release of inflammatory cytokines (PF4, CD40 L and MPO), but also decreased the increment of platelets, neutrophils and platelet-neutrophil aggregates in the fibrotic lung and in the peripheral blood of BLM-treated mice. In addition, cangrelor decreased the number of CD40 and MPO double positive neutrophils and the expression level of CD40 in BLM-treated mouse lungs. Based on these results we conclude that cangrelor alleviates BLM-induced lung inflammation and pulmonary fibrosis in mice, partly through inhibition of platelet activation, therefore reducing the infiltration of neutrophils due to the adhesion of platelets and neutrophils mediated by CD40 - CD40 L interaction. Cangrelor could be a potential therapeutic medicine for pulmonary fibrosis.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Ativação Plaquetária/efeitos dos fármacos , Fibrose Pulmonar/tratamento farmacológico , Monofosfato de Adenosina/uso terapêutico , Animais , Bleomicina/toxicidade , Antígenos CD40/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infiltração de Neutrófilos/efeitos dos fármacos , Infiltração de Neutrófilos/imunologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Ativação Plaquetária/imunologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/imunologia
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