Animals were injected with bleomycin milliporesigma 100. Pirfenidone treatment reduced bleomycininduced pulmonary fibrosis in wildtype but not rgs2 knockout mice. Jci bleomycininduced pulmonary fibrosis in transgenic. Distal airway stem cells ameliorate bleomycininduced. Pulmonary fibrosis is a complex disease for which the predisposing genetic variants remain unknown. We investigated the effects of ahr signals on the process of lung fibrosis and changes in immunological features using a bleomycin blm induced lung fibrosis mouse model. We found that gossypol dosedependently inhibits bleomycininduced collagen accumulation and tgf.
Bleomycin has been widely used in rodents to model pulmonary fibrosis for the study of mechanisms involved in fibrogenesis and for evaluation of potential therapies. To examine the relationship between the fibrinolytic system and pulmonary fibrosis, lung inflammation was induced by bleomycin in transgenic mice that either overexpressed or were completely deficient in murine plasminogen activator inhibitor1 pai1. We first sought to evaluate the effects of curdione on the development of pulmonary fibrosis. Nicorandil ameliorates bleomycin induced pulmonary fibrosis in rats through modulating enos, inos, txnip and hif1.
Preventive effects of vitamin d treatment on bleomycin. Prevention and treatment of bleomycininduced pulmonary fibrosis. The pathogenesis of bleomycininduced pulmonary fibrosis in mice. Background idiopathic pulmonary fibrosis is the most devastating fibrotic diffuse parenchymal lung disease which remains refractory to pharmacological therapies. Bleomycin has been widely used in rodents to model pulmonary fibrosis for the study of mechanisms involved in fibrogenesis and for evaluation of. Cxxc5 attenuates pulmonary fibrosis in a bleomycininduced. The effect of sac on bleomycininduced pulmonary fibrosis in mice. We examined effect of intravenous administration of pcsod on the extent of pulmonary cell death by employing the tunel assay. Thus, the aim of the present study was to determine the role of baicalin in pulmonary fibrosis and fibroblast proliferation in rats. Therapeutic effect of flaxseed oil on experimental pulmonary. Effects of phosphodiesterase 4 inhibition on bleomycin. Attenuation of bleomycin induced pulmonary fibrosis in mice.
The pathogenesis of bleomycininduced pulmonary fibrosis. Oct 21, 2019 furthermore, the expressions of senescence markers, such as p21 and p53, were upregulated upon bleomycin treatment, thereby intensifying the fibrotic condition. In the bleomycin induced pulmonary fibrosis model, tlr2 expression was detected in 29. Apr 18, 2017 oxidative stress is one of the important factors involved in the pathogenesis of idiopathic pulmonary fibrosis ipf. Bleomycin sulfate or saline was administrated intratracheally to mice n 910group at day 0. Pdf zingerone attenuates bleomycininduced pulmonary fibrosis. We investigated the effects of ahr signals on the process of lung fibrosis and changes in immunological features using a bleomycin blminduced lung fibrosis mouse model. Loss of mir29 in bleomycininduced pulmonary fibrosis is smad3dependent.
For this purpose, the mice were administered with curdione for every 2 days, followed by blm injection as described. Accordingly, the molecular pathway mediating the bleomycin. Fibrosis was made in the lungs of rats by bleomycin experimentally. Cxcl11 attenuates bleomycininduced pulmonary fibrosis via.
This study was undertaken to test the hypothesis that the histologic pattern of bleomycin induced lung damage in the chronic stages in the rat does not really mimic the particular histologic pattern of usual interstitial pneumonia uip, the pattern that defines idiopathic pulmonary fibrosis ipf in human beings. The mechanism of bleomycin induced pneumonitis bip involves oxidative damage, relative deficiency of the. Dasatinib attenuated bleomycininduced pulmonary fibrosis in mice article pdf available in growth factors 335 november 2015 with 407 reads how we measure reads. The distal airway stemprogenitor cells dascs have been shown to have potent regenerative capacity after lung injury. Murine candidate bleomycin induced pulmonary fibrosis. Pde5a inhibition attenuates bleomycininduced pulmonary. Cyclosporin a upmodulates bleomycininduced pulmonary. Nicorandil ameliorates bleomycininduced pulmonary fibrosis in rats through modulating enos, inos, txnip and hif1. Pulmonary fibrosis is associated with a poor prognosis. To investigate the role of age formation in pulmonary fibrosis, we used a bleomycin blmstimulated rat model treated with aminoguanidine ag, a crosslink inhibitor of age formation. Curdione attenuated bleomycininduced pulmonary fibrosis in mice.
The administration of bleomycin to rodents has been widely used as an animal model of pulmonary fibrosis, and bleomycin induced pulmonary fibrosis resembles chronic human fibrotic lung disease histologically and physiologically 21, 22, 28, although the tendency for bleomycin induced lung fibrosis in rats to resolve over time is unlike the. Original article inhibition of bleomycininduced pulmonary. Leukotrienes play an important role in ipf, and leukotriene ltb4 is one of the key eicosanoids in ipf. Dasatinib attenuated bleomycininduced pulmonary fibrosis. Phosphodiesterase pde 4 is involved in the processes of remodeling and inflammation, which play key role in tissue fibrosis. Iloprost has protective effect on the pulmonary fibrosis induced by bleomycin and it may be more effective in decreasing fibrotic changes than. Bleomycin induced lung fibrosis is the most frequently used rodent model of lung fibrosis, and produces inflammatory and fibrotic events similar to those seen in human pulmonary fibrosis. Attenuation of bleomycin induced pulmonary fibrosis in.
Receivedforpublication i december 1983 and in revisedform 5 march 1985. Jci bleomycininduced pulmonary fibrosis in fibrinogennull. Nicorandil ameliorates bleomycininduced pulmonary fibrosis in rats through modulating. In this study, we search to evaluate the therapeutic effect of flaxseed oil fo in experimental bleomycin blm induced pulmonary fibrosis. Mouse models of bleomycininduced pulmonary fibrosis. In this study, we search to evaluate the therapeutic effect of flaxseed oil fo in experimental bleomycin blminduced pulmonary fibrosis. In this study, we investigated whether ono4057, a ltb4 receptor bltr antagonist is capable of preventing bleomycin induced pulmonary fibrosis. Idiopathic pulmonary fibrosis ipf is commonly lethal, and current therapies for this disease have little effect on patient prognosis 1, 2. Induction and assessment of bleomycininduced fibrosis. The equilibrium of nuclear factorerythroidrelated factor 2 nrf2btb broadcomplex, tramtrack and bricabrac and cnc capncollar protein homology 1, bach1 determines the expression level of antioxidant factors, further regulating the function of oxidation. Rats were intratracheally instilled with blm 5 mgkg. Bleomycin instillation significantly induced pulmonary fibrosis figure 2a. Here, we employed a mouse model of bleomycininduced pulmonary fibrosis to test whether gossypol inhibits pulmonary fibrosis in vivo.
Pulmonary fibrosis is a progressive and fatal lung disease with limited therapeutic options. Therefore, we next investigated the effect of galectin9 on pulmonary fibrosis induced by bleomycin in mice. This study was undertaken to test the hypothesis that the histologic pattern of bleomycininduced lung damage in the chronic stages in the rat does not really mimic the particular histologic pattern of usual interstitial pneumonia uip, the pattern that. The bleomycin model of pulmonary fibrosis springerlink. Borzone g, moreno r, urrea r et al 2001 bleomycininduced chronic lung damage does not resemble human idiopathic pulmonary fibrosis. The major limitation of bleomycin therapy is pulmonary toxicity, which can be life threatening in up to 10% of patients receiving the drug. Produces single and double stranded breaks in dna uses. We examined whether disrupting skp2 suppressed pulmonary fibrosis in a bleomycin blm induced mouse. Scfskp2 e3 ligase is a target for cancer therapy, but there have been no reports about skp2 as a target for ipf.
Effects of a leukotriene b4 receptor antagonist on bleomycin. Jci bleomycininduced pulmonary fibrosis in transgenic mice. The pathogenesis of fibrotic lung disorders remains unclear, but the extent of tissue damage due to the persistent presence of oxidants or proteases is believed to be important. Among the etiologies are drugs, pulmonary hypertension, hyperoxia, autoimmune diseases, and inhalation of nondegradable fibers and particles 7, 8. Idiopathic pulmonary fibrosis ipf is a devastating disease with poor prognosis. The importance of her2her3 signaling in decreasing the effects of lung injury was recently demonstrated.
Methods pulmonary fibrosis was induced by intranasal instillation of bleomycin into wildtype mice with or without a specific par1 antagonist ie, p1pal12, a pepducin that blocks the par1gprotein interaction. Phan is an established investigator with the american heart association. Cellular senescence and emt crosstalk in bleomycin. We hypothesised that carbon particles, which are major components of cigarette smoke that are transported to alveoli and pleural surface, might be involved in the. The aim of the study was, therefore, to investigate the effect of pde4 inhibition in experimental model of pf. Despite many recent studies, its etiology remains uncertain 1, 3. Amelioration of bleomycininduced pulmonary fibrosis via. Curdione ameliorates bleomycininduced pulmonary fibrosis by. Therapeutic effect of flaxseed oil on experimental. Idiopathic pulmonary fibrosis ipf is a chronic and ultimately fatal. Our findings demonstrate that intratracheal administration of dha, a single pufa, protected mice from the development of bleomycin induced pulmonary inflammation and fibrosis.
Idiopathic pulmonary fibrosis ipf is a progressive disease with poor prognosis and no curative therapies. The major limitation of bleomycin therapy is the potential for lifethreatening interstitial pulmonary fibrosis also called fibrosing alveolitis in up to 10 percent of patients receiving the drug. Bleomycin induces pleural and subpleural fibrosis in the. Other, less common forms of lung injury include organizing pneumonia and hypersensitivity pneumonitis. Jci bleomycininduced pulmonary fibrosis in fibrinogen. As described in the introduction, rosinduced pulmonary cell death and tgf.
Wed like to understand how you use our websites in order to improve them. Dec 01, 2000 mice deleted for the plasminogen activator inhibitor1 pai1 gene are relatively protected from developing pulmonary fibrosis induced by bleomycin. In a prior study, susceptibility to bleomycin induced pulmonary fibrosis was mapped to loci blmpf1 and blmpf2 on chromosomes 17 and 11, respectively, in a c57bl6j b6, susceptible and c3hfkam c3h, resistant mouse cross. The mechanism of bleomycininduced pneumonitis bip involves oxidative damage, relative. Ages level as well as bleomycininduced pulmonary fibrosis is attenuated by ag treatment.
Curdione attenuated bleomycin induced pulmonary fibrosis in mice. Although baicalin can suppress the proliferation of tumor cells, the underlying mechanisms of baicalin in bleomycin blm. Strict guidelines from the committee were followed regarding the care and handling of mice, anesthesia, and. Idiopathic pulmonary fibrosis ipf is a progressive and lethal lung disease. Other, less common forms of lung injury include organizing pneumonia and hypersensitivity pneumonitis 3. The heme degrading enzyme heme oxygenase ho has been found to be expressed in experimental fibrosis, and. Bleomycin, an antineoplastic antibiotic, is known to produce dosedependent. Bleomycininduced pulmonary fibrosis was thought be an inflammatory model, thus other models such as silica or radiationinduced pulmonary fibrosis are need to test the antifibrosis effect. The initial site of injury was the intima of pulmonary arteries and veins where endothelial cells became edematous and were separated from the underlying basement membrane by large blebs. The pathophysiological findings in bleomycin induced.
The present study was performed in accordance with the guidelines of the national institutes of health nih guide for the care and use of. Fibrosis was assessed by hydroxyproline analysis, immunohistochemistry, quantitative pcr and western blot for fibrotic markers expression. Orotracheal treprostinil administration attenuates bleomycin. Idiopathic pulmonary fibrosis is characterized by loss of lung epithelial cells and inexorable progression of fibrosis with no effective and approved treatments. Advanced glycation end products ages have been proposed to be involved in pulmonary fibrosis, but its role in this process has not been fully understood. To test this hypothesis, we used a mouse model of bleomycininduced pulmonary fibrosis that results in severe pah and rv failure. The pathological changes in idiopathic pulmonary fibrosis ipf typically start in subpleural lung regions, a feature that is currently not explained.
The use of bleomycin in the chemotherapy of tumors of lung and skin is limited by the development of interstitial pulmonary fibrosis 1. We hypothesized that pde5 inhibition alters pulmonary and right ventricular rv response to intratracheal bleomycin and that this inhibition acts through suppression of tissue free radicals and the rho kinase pathway. Effects of neutrophil elastase inhibitor on bleomycininduced. Request pdf cyclosporin a upmodulates bleomycininduced pulmonary fibrosis in balbc mice intratracheal instillation of bleomycin bleo into rodents serves as a model for human lung fibrosis. To investigate the role of cxxc5 and the cd40cd40l pathway in lung fibrosis. Blockade of advanced glycation end product formation. The pathophysiological findings in bleomycin induced pulmonary fibrosis in animals resemble those in human ipf, so such fibrosis has been widely used as an animal model for this disease. Aryl hydrocarbon receptor signals attenuate lung fibrosis in. To evaluate the antioxidant effects of pomegranate seed extract pse on bleomycin treated rats. Nicorandil ameliorates bleomycininduced pulmonary fibrosis.
Induction of tenascin in rat lungs undergoing bleomycin. Pdf modeling pulmonary fibrosis with bleomycin researchgate. Bleomycin administration into rodents leads to the accumulation of leukocytes, especially macrophages, followed by the activation of fibroblasts and. Pulmonary fibrosis is the formation of scar tissue in the small air sacs alveoli of the lungs.
Bleomycin is an antineoplastic agent that causes alveolar damage and pulmonary fibrosis as side effects. Bleomycininduced chronic lung damage does not resemble. Bleomycininduced chronic lung damage does not resemble human. Cxcl11 treatment significantly reduced bleomycinincluced pulmonary fibrosis without altering specific lung. Bleomycininduced lung fibrosis is the most frequently used rodent model of lung fibrosis, and produces inflammatory and fibrotic events similar to those seen in human pulmonary fibrosis. Request pdf cyclosporin a upmodulates bleomycin induced pulmonary fibrosis in balbc mice intratracheal instillation of bleomycin bleo into rodents serves as a model for human lung fibrosis. We investigated the effect of treprostinil, a prostacyclin analogue, in bleomycininduced experimental pulmonary fibrosis. On day 1, c57bl6 male mice were given a single intratracheal. Bleomycin is a commonly used chemotherapeutic agent that can cause dosedependent pulmonary fibrosis 5. Pulmonary fibrosis is a component of many interstitial lung diseases, including idiopathic pulmonary fibrosis, a chronic, progressive disease for which there is currently no effective therapy.
Bleomycin is a chemotherapeutic agent commonly used to treat curable diseases such as germinative tumors and hodgkins lymphoma. Sep 15, 2007 bleomycin induced lung fibrosis is the most frequently used rodent model of lung fibrosis, and produces inflammatory and fibrotic events similar to those seen in human pulmonary fibrosis. Idiopathic pulmonary fibrosis is a chronic, progressive, and lethal pulmonary. Ipf, as well as bleomycin induced lung fibrosis, are more common in smokers. Bleomycin has been extensively used in animal models of interstitial lung disease and it produces an acute lung injury response followed by lung fibrosis 6. Attenuation of bleomycininduced pulmonary fibrosis by a. Transgenic mice unable to signal through her2her3 had significantly less bleomycininduced. Inhibiting skp2 e3 ligase suppresses bleomycininduced. Fibrosis is the major characteristic of ssc, and bleomycin has been shown to cause pulmonary fibrosis.
Lung tissue sections were obtained from 15 subjects, including 8 ssc lung explants with pulmonary fibrosis and pulmonary hypertension and 7 control lungs. N induces emt during radiationinduced and bleomycininduced pulmonary fibrosis. Our findings demonstrate that intratracheal administration of dha, a single pufa, protected mice from the development of bleomycininduced pulmonary inflammation and fibrosis. In the bleomycininduced pulmonary fibrosis model, tlr2 expression was detected in 29. Furthermore, the expressions of senescence markers, such as p21 and p53, were upregulated upon bleomycin treatment, thereby intensifying the fibrotic condition. Bleomycin induces dna strand breaks, resulting in pulmonary inflammation, injury, and subsequent interstitial fibrosis. This scarring makes the lungs stiffer and affects the exchange of oxygen and carbon dioxide in the. Pf was induced in c57bl6n mice by instillation of bleomycin. Request pdf cyclosporin a upmodulates bleomycininduced pulmonary fibrosis in balbc mice intratracheal instillation of bleomycin bleo into. Older individuals, particularly those with pulmonary disease, are predisposed to this potentially. Sallyllcysteine attenuates bleomycininduced pulmonary fibrosis. Effects of iloprost on bleomycininduced pulmonary fibrosis in rats.
Compared with the sa group, ages level in lung tissues was markedly increased in the blm group p bleomycin has been extensively used in animal models of interstitial lung disease and it produces an acute lung injury response followed by lung fibrosis 6. Here, we investigated whether genetic disruption of hematopoietic pgd synthase hpgds affects the bleomycin. After stimulating pulmonary fibrosis in spraguedawley rats by endotracheal injection of bleomycin. Curdione ameliorates bleomycininduced pulmonary fibrosis. Prevention and treatment of bleomycininduced pulmonary. Proteaseactivated receptor par1 is a gproteincoupled receptor that mediates critical signalling pathways in pathology and physiology. In this study, we examined the application of diterpene phenol extract of rosmarinus officinalis dero as an antiinflammatory agent for treating bleomycin blm induced pulmonary fibrosis in rat model. Orotracheal aspiration of treprostinil or vehicle was administered daily and started 24 h prior to bleomycin challenge. Cholesterolmodified hydroxychloroquineloaded nanocarriers. Therapeutic effect of lecithinized superoxide dismutase on. Pdf pulmonary delivery of docosahexaenoic acid mitigates. This study has investigated the effect of a synthetic inhibitor of mmp, batimastat, on the development of pulmonary fibrosis induced by bleomycin. Williamson jd, sadofsky lr, hart sp 2015 the pathogenesis of bleomycininduced lung injury in animals and its applicability to human idiopathic pulmonary fibrosis. In a preclinical model, systemic administration of cxcl11 reduced pulmonary collagen deposition, procollagen gene expression, and histopathologic fibroplasia and extracellular matrix deposition in the lung of bleomycintreated mice.
Pdf on mar 3, 2019, mohammad taghi mansouri and others published zingerone attenuates bleomycininduced pulmonary fibrosis in rats. Here we demonstrate that skp2 is a promising therapeutic target for ipf. Pulmonary fibrosis is a chronic progressive disorder in which excessive deposition of extracellular matrix leads to irreversible scarring to interstitial lung tissue. Although it is well known that lipid mediator prostaglandins are involved in the development of pulmonary fibrosis, the role of prostaglandin d2 pgd2 remains unknown. Pulmonary delivery of docosahexaenoic acid mitigates bleomycininduced pulmonary fibrosis. Blm was administered intratracheally to c57bl6jjcl mice and either 5,11dihydroindolo3,2bcarbazole6carboxaldehyde ficz, a natural ahr ligand, or vehicle was. Generally, experimental bleomycin induced pulmonary fibrosis completes within 28 d of the last stimulus 6. These results suggest that further investigations regarding the role of n3 polyunsaturated fatty acids in fibrotic lung injury and repair are needed. Bleomycininduced pulmonary fibrosis is attenuated by a. We hypothesized that pai1 deficiency reduces fibrosis by promoting plasminogen activation and accelerating the clearance of fibrin matrices that accumulate within the damaged lung. In these two mouse models, pulmonary fibrosis is caused by. Pirfenidone attenuates bleomycininduced pulmonary fibrosis. Effects of neutrophil elastase inhibitor on bleomycin. Inken wierstra, in advances in cancer research, 20.
Reduction of bleomycininduced pulmonary fibrosis by serum. Mice deleted for the plasminogen activator inhibitor1 pai1 gene are relatively protected from developing pulmonary fibrosis induced by bleomycin. In this work, we aimed to define the role of mouse dascs mdascs in response to. Aryl hydrocarbon receptor signals attenuate lung fibrosis. Resolution of bleomycininduced murine pulmonary fibrosis via a. Oxidative stress plays an important role in the pathogenesis of bleomycininduced lung fibrosis and many antioxidant agents have been used for the treatment of this disease in animals.
1512 1486 185 1465 60 490 1141 819 625 1522 1323 1074 214 151 729 1470 293 613 511 71 930 1161 1489 986 1462 1114 269 1042 324 237 749 924 44 543 1023 209 1289 116 388 764 1333 1126 1206 483 409 1175 1407 664