First, the toxic effects of curdione to the mice and cells were. The pathological changes in idiopathic pulmonary fibrosis ipf typically start in subpleural lung regions, a feature that is currently not explained. Pulmonary delivery of docosahexaenoic acid mitigates bleomycininduced pulmonary fibrosis. N induces emt during radiationinduced and bleomycininduced pulmonary fibrosis. The mechanism of bleomycininduced pneumonitis bip involves oxidative damage, relative. Transgenic mice unable to signal through her2her3 had significantly less bleomycininduced. Cxcl11 treatment significantly reduced bleomycinincluced pulmonary fibrosis without altering specific lung. Therapeutic effect of flaxseed oil on experimental.
Rats were intratracheally instilled with blm 5 mgkg. We examined effect of intravenous administration of pcsod on the extent of pulmonary cell death by employing the tunel assay. Williamson jd, sadofsky lr, hart sp 2015 the pathogenesis of bleomycininduced lung injury in animals and its applicability to human idiopathic pulmonary fibrosis. Bleomycininduced chronic lung damage does not resemble.
Curdione attenuated bleomycininduced pulmonary fibrosis in mice. Nicorandil ameliorates bleomycininduced pulmonary fibrosis in rats through modulating. The heme degrading enzyme heme oxygenase ho has been found to be expressed in experimental fibrosis, and generation of free iron and carbon monoxide. Pirfenidone attenuates bleomycininduced pulmonary fibrosis. Idiopathic pulmonary fibrosis ipf is commonly lethal, and current therapies for this disease have little effect on patient prognosis 1, 2. Bleomycin instillation significantly induced pulmonary fibrosis figure 2a. To evaluate the antioxidant effects of pomegranate seed extract pse on bleomycin treated rats. Idiopathic pulmonary fibrosis ipf is a progressive and lethal lung disease. For this purpose, the mice were administered with curdione for every 2 days, followed by blm injection as described.
Effects of phosphodiesterase 4 inhibition on bleomycin. 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. Prevention and treatment of bleomycininduced pulmonary. Fibrosis was assessed by hydroxyproline analysis, immunohistochemistry, quantitative pcr and western blot for fibrotic markers expression. Curdione ameliorates bleomycininduced pulmonary fibrosis by. Bleomycin is a commonly used chemotherapeutic agent that can cause dosedependent pulmonary fibrosis 5.
Therapeutic effect of flaxseed oil on experimental pulmonary. 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. Aryl hydrocarbon receptor signals attenuate lung fibrosis. Dec 01, 2000 mice deleted for the plasminogen activator inhibitor1 pai1 gene are relatively protected from developing pulmonary fibrosis induced by bleomycin. We examined whether disrupting skp2 suppressed pulmonary fibrosis in a bleomycin blm induced mouse. Inhibiting skp2 e3 ligase suppresses bleomycininduced. We investigated the effect of treprostinil, a prostacyclin analogue, in bleomycininduced experimental pulmonary fibrosis. Nicorandil ameliorates bleomycininduced pulmonary fibrosis in rats through modulating enos, inos, txnip and hif1. 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. The major limitation of bleomycin therapy is pulmonary toxicity, which can be life threatening in up to 10% of patients receiving the drug. 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. Although baicalin can suppress the proliferation of tumor cells, the underlying mechanisms of baicalin in bleomycin blm. Induction of tenascin in rat lungs undergoing bleomycin.
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. Dasatinib attenuated bleomycininduced pulmonary fibrosis in mice article pdf available in growth factors 335 november 2015 with 407 reads how we measure reads. In this work, we aimed to define the role of mouse dascs mdascs in response to. We hypothesized that pai1 deficiency reduces fibrosis by promoting plasminogen activation and accelerating the clearance of fibrin matrices that accumulate within the damaged lung. Other, less common forms of lung injury include organizing pneumonia and hypersensitivity pneumonitis.
Reduction of bleomycininduced pulmonary fibrosis by serum. 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. The bleomycin model of pulmonary fibrosis springerlink. Phan is an established investigator with the american heart association. Induction and assessment of bleomycininduced fibrosis. Prevention and treatment of bleomycininduced pulmonary fibrosis. On day 1, c57bl6 male mice were given a single intratracheal.
Therapeutic effect of lecithinized superoxide dismutase on. Fibrosis was made in the lungs of rats by bleomycin experimentally. Resolution of bleomycininduced murine pulmonary fibrosis via a. 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. Scfskp2 e3 ligase is a target for cancer therapy, but there have been no reports about skp2 as a target for ipf.
Effects of iloprost on bleomycininduced pulmonary fibrosis in rats. 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. Dasatinib attenuated bleomycininduced pulmonary fibrosis. Jci bleomycininduced pulmonary fibrosis in transgenic mice. After stimulating pulmonary fibrosis in spraguedawley rats by endotracheal injection of bleomycin.
This study has investigated the effect of a synthetic inhibitor of mmp, batimastat, on the development of pulmonary fibrosis induced by bleomycin. In the bleomycin induced pulmonary fibrosis model, tlr2 expression was detected in 29. Cxcl11 attenuates bleomycininduced pulmonary fibrosis via. Older individuals, particularly those with pulmonary disease, are predisposed to this potentially. Inken wierstra, in advances in cancer research, 20. 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. Attenuation of bleomycin induced pulmonary fibrosis in mice. Idiopathic pulmonary fibrosis is characterized by loss of lung epithelial cells and inexorable progression of fibrosis with no effective and approved treatments. Animals were injected with bleomycin milliporesigma 100. In this study, we search to evaluate the therapeutic effect of flaxseed oil fo in experimental bleomycin blminduced pulmonary fibrosis.
Pdf on mar 3, 2019, mohammad taghi mansouri and others published zingerone attenuates bleomycininduced pulmonary fibrosis in rats. Pulmonary fibrosis is a progressive and fatal lung disease with limited therapeutic options. Apr 18, 2017 oxidative stress is one of the important factors involved in the pathogenesis of idiopathic pulmonary fibrosis ipf. 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.
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. The pathogenesis of bleomycininduced pulmonary fibrosis in mice. Distal airway stem cells ameliorate bleomycininduced. 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. Amelioration of bleomycininduced pulmonary fibrosis via. Oct 21, 2019 furthermore, the expressions of senescence markers, such as p21 and p53, were upregulated upon bleomycin treatment, thereby intensifying the fibrotic condition. Pulmonary fibrosis is a chronic progressive disorder in which excessive deposition of extracellular matrix leads to irreversible scarring to interstitial lung tissue. Bleomycin, an antineoplastic antibiotic, is known to produce dosedependent. Aryl hydrocarbon receptor signals attenuate lung fibrosis in. The importance of her2her3 signaling in decreasing the effects of lung injury was recently demonstrated. Cellular senescence and emt crosstalk in bleomycin. Borzone g, moreno r, urrea r et al 2001 bleomycininduced chronic lung damage does not resemble human idiopathic pulmonary fibrosis. 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.
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. 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. Nicorandil ameliorates bleomycininduced pulmonary fibrosis. 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. Original article inhibition of bleomycininduced pulmonary. Pirfenidone treatment reduced bleomycininduced pulmonary fibrosis in wildtype but not rgs2 knockout mice. Loss of mir29 in bleomycininduced pulmonary fibrosis is smad3dependent. Produces single and double stranded breaks in dna uses. Iloprost has protective effect on the pulmonary fibrosis induced by bleomycin and it may be more effective in decreasing fibrotic changes than.
The pathophysiological findings in bleomycin induced. This scarring makes the lungs stiffer and affects the exchange of oxygen and carbon dioxide in the. Background idiopathic pulmonary fibrosis is the most devastating fibrotic diffuse parenchymal lung disease which remains refractory to pharmacological therapies. Pdf modeling pulmonary fibrosis with bleomycin researchgate. Blm was administered intratracheally to c57bl6jjcl mice and either 5,11dihydroindolo3,2bcarbazole6carboxaldehyde ficz, a natural ahr ligand, or vehicle was. Therefore, we next investigated the effect of galectin9 on pulmonary fibrosis induced by bleomycin in mice. The mechanism of bleomycin induced pneumonitis bip involves oxidative damage, relative deficiency of the. Attenuation of bleomycin induced pulmonary fibrosis in.
Lung tissue sections were obtained from 15 subjects, including 8 ssc lung explants with pulmonary fibrosis and pulmonary hypertension and 7 control lungs. Receivedforpublication i december 1983 and in revisedform 5 march 1985. Effects of neutrophil elastase inhibitor on bleomycin. 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. Fibrosis is the major characteristic of ssc, and bleomycin has been shown to cause pulmonary fibrosis. Accordingly, the molecular pathway mediating the bleomycin. Pulmonary fibrosis is associated with a poor prognosis. Pulmonary fibrosis is the formation of scar tissue in the small air sacs alveoli of the lungs. To test this hypothesis, we used a mouse model of bleomycininduced pulmonary fibrosis that results in severe pah and rv failure. 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. Murine candidate bleomycin induced pulmonary fibrosis.
Bleomycin is a chemotherapeutic agent commonly used to treat curable diseases such as germinative tumors and hodgkins lymphoma. 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 distal airway stemprogenitor cells dascs have been shown to have potent regenerative capacity after lung injury. Idiopathic pulmonary fibrosis ipf is a chronic and ultimately fatal. Effects of neutrophil elastase inhibitor on bleomycininduced. Request pdf cyclosporin a upmodulates bleomycininduced pulmonary fibrosis in balbc mice intratracheal instillation of bleomycin bleo into.
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. The present study was performed in accordance with the guidelines of the national institutes of health nih guide for the care and use of. Thus, the aim of the present study was to determine the role of baicalin in pulmonary fibrosis and fibroblast proliferation in rats. Generally, experimental bleomycin induced pulmonary fibrosis completes within 28 d of the last stimulus 6. Pf was induced in c57bl6n mice by instillation of bleomycin. The effect of sac on bleomycininduced pulmonary fibrosis in mice. In this study, we search to evaluate the therapeutic effect of flaxseed oil fo in experimental bleomycin blm induced pulmonary fibrosis. Galectin9 deficiency attenuated bleomycininduced lung fibrosis. Orotracheal aspiration of treprostinil or vehicle was administered daily and started 24 h prior to bleomycin challenge. Idiopathic pulmonary fibrosis ipf is a devastating disease with poor prognosis.
Our findings demonstrate that intratracheal administration of dha, a single pufa, protected mice from the development of bleomycin induced pulmonary inflammation and fibrosis. The use of bleomycin in the chemotherapy of tumors of lung and skin is limited by the development of interstitial pulmonary fibrosis 1. Orotracheal treprostinil administration attenuates bleomycin. 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. Ipf, as well as bleomycin induced lung fibrosis, are more common in smokers. 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. Furthermore, the expressions of senescence markers, such as p21 and p53, were upregulated upon bleomycin treatment, thereby intensifying the fibrotic condition.
Pdf pulmonary delivery of docosahexaenoic acid mitigates. Bleomycin is an antineoplastic agent that causes alveolar damage and pulmonary fibrosis as side effects. Bleomycin induces pleural and subpleural fibrosis in the. 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. In this study, we investigated whether ono4057, a ltb4 receptor bltr antagonist is capable of preventing bleomycin induced pulmonary fibrosis. The pathogenesis of bleomycininduced pulmonary fibrosis. 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. Bleomycininduced pulmonary fibrosis is attenuated by a. Jci bleomycininduced pulmonary fibrosis in fibrinogennull. 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.
Sallyllcysteine attenuates bleomycininduced pulmonary fibrosis. Bleomycin sulfate or saline was administrated intratracheally to mice n 910group at day 0. Our findings demonstrate that intratracheal administration of dha, a single pufa, protected mice from the development of bleomycininduced pulmonary inflammation and fibrosis. Other, less common forms of lung injury include organizing pneumonia and hypersensitivity pneumonitis 3. 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.
In these two mouse models, pulmonary fibrosis is caused by. Mouse models of bleomycininduced pulmonary fibrosis. 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. Here, we employed a mouse model of bleomycininduced pulmonary fibrosis to test whether gossypol inhibits pulmonary fibrosis in vivo. Cyclosporin a upmodulates bleomycininduced pulmonary. Among the etiologies are drugs, pulmonary hypertension, hyperoxia, autoimmune diseases, and inhalation of nondegradable fibers and particles 7, 8. 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. These results suggest that further investigations regarding the role of n3 polyunsaturated fatty acids in fibrotic lung injury and repair are needed. We found that gossypol dosedependently inhibits bleomycininduced collagen accumulation and tgf. 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. Blockade of advanced glycation end product formation. As described in the introduction, rosinduced pulmonary cell death and tgf. Ages level as well as bleomycininduced pulmonary fibrosis is attenuated by ag treatment.
Effects of a leukotriene b4 receptor antagonist on bleomycin. Bleomycin has been widely used in rodents to model pulmonary fibrosis for the study of mechanisms involved in fibrogenesis and for evaluation of. Pdf zingerone attenuates bleomycininduced pulmonary fibrosis. Pulmonary fibrosis pf is a group of devastating and largely irreversible diseases. Jci bleomycininduced pulmonary fibrosis in transgenic. Bleomycin administration into rodents leads to the accumulation of leukocytes, especially macrophages, followed by the activation of fibroblasts and. To investigate the role of cxxc5 and the cd40cd40l pathway in lung fibrosis. Cholesterolmodified hydroxychloroquineloaded nanocarriers. Leukotrienes play an important role in ipf, and leukotriene ltb4 is one of the key eicosanoids in ipf. Preventive effects of vitamin d treatment on bleomycin. 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. Bleomycin induces dna strand breaks, resulting in pulmonary inflammation, injury, and subsequent interstitial fibrosis. The aim of the study was, therefore, to investigate the effect of pde4 inhibition in experimental model of pf. Cxxc5 attenuates pulmonary fibrosis in a bleomycininduced.
Curdione attenuated bleomycin induced pulmonary fibrosis in mice. Here, we investigated whether genetic disruption of hematopoietic pgd synthase hpgds affects the bleomycin. Despite many recent studies, its etiology remains uncertain 1, 3. Curdione ameliorates bleomycininduced pulmonary fibrosis. Strict guidelines from the committee were followed regarding the care and handling of mice, anesthesia, and.
Idiopathic pulmonary fibrosis ipf is a progressive disease with poor prognosis and no curative therapies. Here we demonstrate that skp2 is a promising therapeutic target for ipf. The heme degrading enzyme heme oxygenase ho has been found to be expressed in experimental fibrosis, and. In the bleomycininduced pulmonary fibrosis model, tlr2 expression was detected in 29. Proteaseactivated receptor par1 is a gproteincoupled receptor that mediates critical signalling pathways in pathology and physiology. 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. Jci bleomycininduced pulmonary fibrosis in fibrinogen. 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. Pde5a inhibition attenuates bleomycininduced pulmonary. Attenuation of bleomycininduced pulmonary fibrosis by a. Phosphodiesterase pde 4 is involved in the processes of remodeling and inflammation, which play key role in tissue fibrosis.