• Tuberculosis and Respiratory Diseases
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• v.56 no.1
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• pp.51-66
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• 2004

Objectives : The matrix metalloproteinases (MMPs) that participate in the extracellular matrix metabolism play a important role in the progression of pulmonary fibrosis. The effects of the MMPs are regulated by several factors including Th-1 cytokines, $interferon-{\gamma}$ ($IFN-{\gamma}$). Up to now, $IFN-{\gamma}$ is known to inhibit pulmonary fibrosis, but little is known regarding the exact effect of $IFN-{\gamma}$ on the regulation of the MMPs. This study investigated the effects of $interferon-{\gamma}$ on the pulmonary fibrosis and the expression of the lung MMP-2,-9, TIMP-1,-2, and Th-2 cytokines in aa rat model of bleomycin induced pulmonary fibrosis. Materials and methods : Male, specific pathogen-free Sprague-Dawley rats were subjected to an intratracheal bleomycin instillation. The rats were randomized to a saline control, a bleomycin treated, and a bleomycin+$IFN-{\gamma}$ treated group. The bleomycin+$IFN-{\gamma}$ treated group was subjected to an intramuscular injection of $IFN-{\gamma}$ for 14 days. At 3, 7, 14, and 28 days after the bleomycin instillation, the rats were sacrificed and the lungs were harvested. In order to evaluate the effects of the $IFN-{\gamma}$ on lung fibrosis and inflammation, the lung hydroxyproline content, inflammation and fibrosis score were measured. Western blotting, zymography and reverse zymography were performed at 3, 7, 14, 28 days after bleomycin instillation in order to evaluate the MMP-2,-9, and TIMP-1,-2 expression level. ELISA was performed to determine the IL-4 and IL-13 level in a lung homogenate. Results : 1. 7 days after bleomycin instillation, inflammatory changes were more severe in the bleomycin+$IFN-{\gamma}$ group than the bleomycin group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$2.08{\pm}0.15:2.74{\pm}0.29$, P<0.05), but 28 days after bleomycin instillation, lung fibrosis was significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$3.94{\pm}0.43:2.64{\pm}0.13$, P<0.05). 2. 28 days after bleomycin instillation, the lung hydroxyproline content was significantly reduced as a result of $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$294.04{\pm}31.73{\mu}g/g:194.92{\pm}15.51{\mu}g/g$, P<0.05). 3. Western blotting showed that the MMP-2 level was increased as a result of the bleomycin instillation and highest in the 14 days after bleomycin instillation. 4. In zymography, the active forms of MMP-2 were significantly increased as a result of the $IFN-{\gamma}$ treatment 3 days after the bleomycin instillation, bleomycin+$IFN-{\gamma}$ group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$209.63{\pm}7.60%:407.66{\pm}85.34%$, P<0.05), but 14 days after the bleomycin instillation, the active forms of MMP-2 were significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$159.36{\pm}20.93%:97.23{\pm}12.50%$, P<0.05). 5. The IL-4 levels were lower in the bleomycin and bleomycin+$IFN-{\gamma}$ groups but this was not significant, and the IL-13 levels showed no difference between the experiment groups. Conclusion : The author found that lung inflammation was increased in the early period but the pulmonary fibrosis was inhibited in the late stage as a result of $IFN-{\gamma}$. The inhibition of pulmonary fibrosis by $IFN-{\gamma}$ appeared to be associated with the inhibition of MMP-2 activation by $IFN-{\gamma}$. Further studies on the mechanism of the regulation of MMP-2 activation and the effects of MMP-2 activation on pulmonary fibrosis is warranted in the future.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.5 no.1
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• pp.77-101
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• 1999

l. Sojeokbaekchoolsan compound treatment decreased pulmonary fibrosis induced by Bleomycin. 2. At 1 and 2 days after bleomycin treatment, Sojeokbaekchoolsan compound treatment decreased the number of neutrophils in bronchoalveolar lavage than those of bleomycin alone treatment. 3. Sojeokbaekcoolsan compound treatment increased the Fc receptor mediated rosette activity of alveolar macrophage decreased by bleomycin treatment. 4, At 10 days after bleomycin treatment, Sojeokbaekchoolsan compound treatment decreased the lipid peroxidation of lung tissue than those of bleomycin alone treatment. 5. Anti-tumor activity of Sojeokbaekchoolsan and bleomycin compound group was higher than those of bleomycin alone treated group to ascitic tumor caused by Sarcoma-180 tumor cells.

• Environmental Mutagens and Carcinogens
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• v.17 no.1
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• pp.12-16
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• 1997

Chromosome rearrangement induced by bleomycin were identified by fluorescence in situ hybridization with probe for chromosome 4. The frequency of color junctions, translocations, dicentric and acenttic fragments increased with bleomycin dose. Different types of balanced translocation and dicentric were scored and compared. The frequency of cells exhibiting multiple aberration was higher compared to that of cells exposed to Gamma radiation suggesting that effect of bleomycin might be similar to that of high LET radiation.

• Journal of Chest Surgery
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• v.22 no.6
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• pp.914-920
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• 1989

Bleomycin and cyclophosphamide are widely used and effective anti-cancer agents for treatment of various forms of cancer. Bleomycin has no myelotoxicity, but because of potential risk of pulmonary complications including interstitial pneumonitis and idiopathic interstitial pulmonary fibrosis, it has been limited in use. Some investigator has also suggested that cyclophosphamide can induce pulmonary toxicity like bleomycin. Recently, The combination chemotherapy including bleomycin and cyclophosphamide has been adopted effectively in some types of cancer. But there are no available literatures for synergistic effect of pulmonary toxicity in combination chemotherapy including these two drugs. We tried this study to observe synergism of pulmonary toxicity using these two drugs in rats. The animals were divided into five groups: group 1 received intra-peritoneal injection of saline, group 2-a received only bleomycin 0.1 mg [0.4 mg/kg] by intra-peritoneal injection twice a week, group 2-b received only bleomycin 0.5 mg [2 mg/kg] by intra-peritoneal injection twice a week, group 3-a received bleomycin 0.1 mg [0.4 mg/kg] twice a week +cyclophosphamide 5 mg [20 mg/kg] two weeks interval by intra-peritoneal injection, group 3-b received bleomycin 0.5 mg [2 mg/kg] twice a week + cyclophosphamide 5 mg[20 mg/kg] two weeks interval by intra-peritoneal injection. The animals were sacrificed at 2 and 4 weeks later. Lung tissues were obtained and observed by light microscope. The results are as follows: 1. The pathologic findings of group 1 were normal without change. 2. There was no difference between group 2-a and group 3-a at 2 weeks later, group 3-a, however, revealed more severe change in lung tissue at 4 weeks later compared with group 2-a. 3. In group 3-b there was more severe pulmonary injury compared with group 2-b at 2 and 4 weeks later. We conclude that the combined administration of bleomycin and cyclophosphamide induce more severe pulmonary toxic effect than bleomycin administration alone and the combination chemotherapy including these two drugs will be require special attention to selection of the dose of each drug.

• Journal of Haehwa Medicine
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• v.29 no.1
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• pp.1-17
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• 2020

Objectives : The objectives of this study is to develop a mouse model similar to Taeeum-type by inducing Lung fibrosis with bleomycin, and to determine adequate concentration of bleomycin. Methods : The subjects were divided into six groups: normal, obesity induced group, and bleomycin administered 0.015U, 0.03U, 0.06U, and 0.09U(U/100g bw) concentrations respectively. Each concentration of bleomycin was dissolved in distilled water, and administered through Intra-Nazal-Trachea injection method. Food intake and body weight were measured at regular time weekly. At the end of the experiment, blood was gathered by cardiac puncture for biochemical examinations, organs were removed for histological examinations, and weigh and mRNA genes was analyzed. Result : Mice administered with bleomycin at 0.015U and 0.03U showed body and fat weight gain, and increased blood total cholesterol, LDL-cholesterol, glucose, and free fatty acid level. Fat related genes also showed higher level than the control group. Obesity was most strongly induced in the mice administered with 0.03U of bleomycin. On the other hand, when bleomycin was administered at concentrations above 0.06U, a model of obesity mouse was not created due to rapid emphysema inflammation and weakness. Conclusions : Mice were most vulnerable to obesity when bleomycin was administered at a concentration of 0.3 to cause liver damage. Bleomycin concentration over 0.06U did not cause obesity-induced mice, due to severe damage in liver.

• Journal of Chest Surgery
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• v.41 no.6
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• pp.791-794
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• 2008

Pneumomediastinum is a rare, but well recognized complication of bleomycin-induced lung toxicity. Spontaneous pneumomediastinum has to be considered as one of the causes when the dyspnea becomes aggravated in patients with bleomycin induced lung toxicity. We describe here two patients who suffered with germ cell tumor and they developed spontaneous pneumomediastinum without pneumothorax, and this was caused by bleomycin-induced lung toxicity.

• Journal of Environmental Health Sciences
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• v.19 no.4
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• pp.59-66
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• 1993

The cellular toxicity and antitumor effects of bleomycin are thought to be occurred by formation of O$_2$-Fe$^{2+}$-bleomycin complexes that degrade DNA and release O$_2^-$ and $^{\cdot}$OH radicals. Hydroxyl radicals derived from hydrogen peroxide seem most likely to be involved in the various stages of carcinogenesis, and transition metals such as iron play a central role in activation of bleomycin and in formation of hydroxyl radicals. This study was performed to investigate whether treatment with ferrous sulfate increase chromosome aberration induced by bleomycin and hydrogen peroxide, and whether there is different repair mechanism for DNA damage induced by those chemicals. Treatment with 3AB, Ara C, during G$_1$ and post-treatment with caffeine, and Hu during G$_2$ increased the frequency of chromosome aberration induced by bleomycin but post-treatment with caffeine only did function that way when hydrogen peroxide was treated. When 6.6X 10$^{-7}$ M of bleomycin or 5.0X10$^{-5}$M of hydrogen peroxide were treated simultaneously with iron, the frequency of chromosome aberration was reduced, if compared with the results by bleomycin or hydrogen per oxide alone.

• The Korean Journal of Zoology
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• v.20 no.1
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• pp.41-48
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• 1977

Dose response of DNA repair synthesis induced by bleomycin was dose-dependent in lower doses, and maximum rate of it at 5 $\\mu$g/ml represents about 15% of total cells analyzed. At higher doses DNA-repair synthesis was reduced and the rate of it remained unchanged even prolonged treatment. Pretreatment with BUdR or IUdR was found to enhance DNA repair synthesis and also to interfere with semiconservative DNA synthesis at higher doses. Time dependence study showed that DNA repair synthesis occurred as long as for 24 hours after removal of bleomycin. These results seem to suggest that bleomycin is not to be an effective chemical in inducing excision repair and that damages induced in DNA by this drug might include not only strand breaks but other types of DNA damage.

• Journal of Environmental Health Sciences
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• v.18 no.2
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• pp.117-124
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• 1992

Pretreatment with low concentration of Bleomycin and Cadmium rendered Chinese Hamster Ovary Cells more resistant to the induction of chromosome aberration by subsequent high concentration of same agent, however Mitomycin C did not function in that way. The cells pre-exposed to low dose of Cadmitim did not show cross-resistance to challenge dose of Mitomycin C for the induction of chromosome aberration, but cells pre-exposed to Bleomycin showed cross resistance. And the cells pre-exposed to low dose of Mitomycin C showed cross resistance to challenge of Bleomycin, but Cadmium did not.

• Tuberculosis and Respiratory Diseases
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• v.44 no.1
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• pp.85-92
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• 1997

Background : The standard treatment of recurrent, symptomatic malignant pleural effusion is intrapleural instillation of a chemical agent in an attempt to achieve a sterile inflammation and pleurodesis. There are many drugs used as pleural sclerosing agents, but the efficiency and side effects are different. The present study was undertaken to compare the commonly used drugs, doxycycline and bleomycin. Methods : Thirty-four patients with malignant pleural effusion who needed repeated thoracentesis were randomized to receive treatment with intrapleural instillation of doxycycline or bleomycin Fluid volumes before and after pleurodesis, drainge time, and side effects were analyzed, and the response to treatment was evaluated by clinical examination and chest radiography during admission in the hospital. Also median survival rime were evaluated according to the responses. Results : The response rate was higher in the patients receiving doxycycline than in those receiving bleomycin (87.5% vs 50.0%, p=0.02), and fever, nausea and vomiting were more common in the patients receiving bleomycin. The median survival time was significantly longer in the patients who responded to the sclerotherapy regardless of sclerosing agents. Conclusions : Chemical pleurodesis with doxycycline or bleomycin could reduce or stop pleural effusions and prolong the median survival rimes in these patients. Doxycycline appeared to be more efficient as sclerosing agent than bleomycin in the short-term follow-up periods. But a prospective study with a larger number of patients is warranted.