• Tuberculosis and Respiratory Diseases
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• v.52 no.3
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• pp.260-264
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• 2002

Bleomycin-induced pulmonary toxicity usually occurs in the elderly patients (greater than 70 years old), patients with a cumulative dose above 400 units, previous chest radiotherapy, oxygen therapy, and renal failure. However, there are some reports of severe pneumonitis that developed after administering low bleomycin doses(less than 100 units). In severe bleomycin-induced pneumonitis in non-Hodgkin's lymphoma patients, the response to corticosteroid is poor and the mortality rate is very high, approximately 83%. Therefore, clinicians should have a low threshold for investigating and treating bleomycin-induced pneumonitis. Here, we report a case of severe bleomycin-induced pneumonitis as a complication of a non-Hodgkin's lymphoma treatment.

• Tuberculosis and Respiratory Diseases
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• v.42 no.2
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• pp.184-205
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• 1995

Background: Pulmonary toxicity by bleomycin has multiple mechanisms including direct tissue toxicity due to oxygen-derived free radicals and indirect toxicity through amplification of pulmonary inflammation. To evaluate the effect of chelators or free radical scavenger to lung damage induced by bleomycin, penicillamine as a copper chelator, deferoxamine as an iron chelator and vitamin E as a free radical scavenger were administered. Methods: Two hundred Wistar rats were divided into five groups: Control, bleomycin treated, bleomycin-penicillamine treated, bleomycin-deferoxamine treated, and bleomycin-vitamin E treated groups. Rats sacrificed on day 1, day 3, day 4, day 7, day 14, and day 28 after treatment. Bronchoalveolar lavage, light microscopic and immunohistologic studies for type I, III, IV collagens, fibronectin, laminin and NBD phallicidin were evaluated. Results: There was a significant increase in the total cell counts of bronchoalveolar lavage on day 1 from all treated animals and vitamin treated group showed an abrupt decrease in total cell counts with decrease of neutrophils on day 3. Bleomycin-vitamin E treated group had the least histologic changes such as pulmonary fibrosis. The alveolar basement membranes were positive for type IV collegen and laminin. Basement membranes of bleomycin, bleomycin-penicillamine, or bleomycin-deferoxamine treated groups were disrupted and fragmented on day 4 or 7. The bleomycin-vitamin E treated group had intact basement membranes until day 28. Conclusion: Bleomycin-induced pulmonary fibrosis was related to the severity of acute injury to oxygen radicals or activation of neutrophils and disruption of basement membrane. Vitamin E seemed to be the most effective antioxidant in the inhibition of bleomycin-induced pulmonary injury and fibrosis.

• Environmental Mutagens and Carcinogens
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• v.15 no.2
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• pp.88-93
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• 1995

Effects of hyperthermia on the induction of DNA single strand breaks and replication inhibition were studied in bleomycin-treated CHO-K$_1$ cells by alkaline elution and alkaline sucrose gradient sedimentation. Bleomycin-induced DNA single strand breaks of DNA were dose-and time-dependently increased, and these strand breaks of DNA were gradually rejoined as post-incubation time passed. Treatment with hyperthermia alone did not affect the induction of DNA single strand breaks. However, pre-exposure of cells to hyperthermia followed by bleomycin treatment greatly increased the single strand breaks, and also reduced the rejoining processes of bleomycin-induced DNA single strand breaks. Bleomycin selectively inhibited the replicon initiation. The combined treatment with hyperthermia and bleomycin markedly potentiated the nonspecific inhibition of replication.

• Toxicological Research
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• v.26 no.3
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• pp.217-222
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• 2010

Many studies have reported that bleomycin, anti-cancer drug, induces pulmonary fibrosis as a side effect. However, few investigations have focused on the dose-response effects of bleomycin on pulmonary fibrosis. Therefore, in the present study, we investigated the effects of different doses of bleomycin in male mice. ICR mice were given 3 consecutive doses of bleomycin: 1, 2, or 4 mg/kg in bleomycin-treated (BT) groups and saline only in vehicle control (VC) groups. The animals were sacrificed at 7 and 24 days postinstillation. The severity of pulmonary fibrosis was evaluated according to inflammatory cell count and lactate dehydrogenase (LDH) activity in the broncho alveolar lavage fluid (BALF), and lung tissues were histologically evaluated after hematoxylin and eosin (H&E), and Masson's trichrome staining. BT groups exhibited changed cellular profiles in BAL fluid compared to the VC group, which had an increased number of total cells, neutrophils, and lymphocytes and a modest increase in the number of macrophages at 7 days post-bleomycin instillation. Moreover, BT groups showed a dose-dependent increase in LDH levels and inflammatory cell counts. However, at 24 days after treatment, collagen deposition, interstitial thickening, and granulomatous lesions were observed in the alveolar spaces in addition to a decrease in inflammatory cells. These results indicate that pulmonary fibrosis induced by 4 mg/kg bleomycin was more severe than that induced by 1 or 2 mg/kg. These data will be utilized in experimental animal models and as basic data to evaluate therapeutic candidates through non-invasive monitoring using the pulmonary fibrosis mouse model established in this study.

• The Journal of Pediatrics of Korean Medicine
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• v.24 no.1
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• pp.126-133
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• 2010

Objectives In this study, we evaluated the therapeutic effects of Gami-Bojungikgitang and Gami-Jwagwieum for bleomycin-induced lung fibrosis in mice. Methods Extracted lyophilization, Gami-Bojungikgitang (96g) and Gami-Jwagwieum (118g) boiled, filtered, depressed, concentrated, and are obtained. They were divided into five groups: normal, group IA; Animal group treated with bleomycin observed on the 21th day, group IB; Animal group treated with bleomycin observed on the 42th day, group IIA; Animal group treated with bleomycin and Gami-Bojungikgitang. Gami-Jwagwieum observed on the 21th day, group IIB; Animal group treated with bleomycin and Gami-Bojungikgitang/Gami-Jwagwieum observed on the 42th day. Mice are used on the 42th day and as a result, bronchoalveolar lavages fluid is obtained. Counting total number of cells, different ratio of macrophage, lymphocyte, and neutrophil are established. Results In animal group treated with bleomycin and Gami-Bojungikgitang, total cell count decreased by 50% in 3 weeks compared to animal group with non-administrated Gami-Bojungikgitang. However, total cell count in 6 weeks increased compared to 3 weeks although total cell count still decreased compared to animal group with non-administrated Gami-Bojungikgitang. In the view of differential cell counts in bronchoalveolar lavages fluid in treatment group on 3 and 6 weeks, neutrophile was a few and lymphocyte decreased. In animal group treated with bleomycin and Gami-Jwagwieum, total cell count decreased by 50% in 3 and 6 weeks compared to animal group with non-administrated Gami-Jwagwieum. In the view of differential cell counts in bronchoalveolar lavages fluid in treatment group on 3 and 6 weeks, lymphocyte also decreased. Conclusions Gami-Bojungikgitang and especially Gami-Jwagwieum for bleomycin-induced lung fibrosis in mice were effective in total cell count and differential cell count.

• Journal of Sasang Constitutional Medicine
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• v.28 no.2
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• pp.147-162
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• 2016

Objectives The objective of this study is to develop a taeeumin animal-experimental model induced lung fibrosis with Bleomycin and evaluate the effect on obesity in this animal-experimental model.Methods The subjects were divided into 3 groups : normal group, high fat diet(HFD) control group, and HFD group administered with bleomycin(n=10 per group). To develop taeeumin animal-experimental model with reduced respiratory metabolism, 8-week-old C57BL/6 mice were administered with 0.03ml solution of bleomycin 1U/ml dissolved in distilled water, intratracheal(IT), once. Then, the HFD control group and the experimental group were fed with high fat diet for 6 weeks. Airway hyperresponsiveness(AHR) to methacholine was measured at the 1st and 3rd week after bleomycin was administered. Food intake and body weight were measured at regular time weekly. After the final experiment, blood was gathered by cardiac puncture for bloodchemical examination and organs(liver, fatty tissue) were remoed, weighted, and mRNA was analyzed.Results and Conclusions Through the experiment, it was found that Bleomycin induced Taeeumin animal-experimental models have leptin resistace. In the experimental group administered with Bleomycin, fatty acid synthesizing gene expression increased and energy metabolizing gene expression decreased. As mRNA expression of adiponectin decreased, it was found that Taeeuim animal-experimental model is susceptible to metabolic syndrome and cardiovascular diseases.

• The Journal of Internal Korean Medicine
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• v.25 no.1
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• pp.71-80
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• 2004

Objective : Idiopathic Lung Fibrosis(IPF) is chronic fibrotic interstitial pneumonia. The pathogenesis is unclear. Lonicerae Flos is known to prevent the inflammation and reinforce the immune system. The effects of Lonicerae Flos on bleomycin-induced lung fibrosis is evaluated. Material and Methods: Lonicerae Flos extract was given to the Normal rats, control(bleomycin) rats everyday and treated(bleomycin and lonicerae flos) rats 21.0 mg per body weight 109 for 14 days. 14 days after, we observed the change of leukocyte count and percentage of IFN-gamma and IL-4 in BALF. and that of Semiquantative histological index(SHI). Results : Compared to control rats, Lonicerae Flos decreased leukocyte count(P<0.01) lymphocyte, neutrophil percentage(P<0.05), SHI(P<0.01), IFN-gamma and IL-4(P<0.05) in Treated rats. Otherwise, macrophage percentage was increased(P<0.01) in Treated rats. Conclusion : This study showed that Lonicerae Flos reduced the change of inflammatory cells and cytokines in bleomycin-induced lung fibrosis and reduced the fibrosis of tissue. And, we needed many other distinct researches on lung fibrosis.

• The Journal of Korean Medicine
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• v.25 no.2
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• pp.41-50
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• 2004

Backgrounds & Objectives: Many acute and chronic lung disorders with variable degrees of pulmonary inflammation and fibrosis are collectively referred to as interstitial lung diseases. Idiopathic pulmonary fibrosis (IPF) is one of several idiopathic interstitial pneumonias with the pathogenesis unclear. Astragali Radix is known to inhibit the Th2 immune response. The effects of Astragali Radix on bleomycin-induced lung fibrosis were evaluated. Materials and Methods: Astragali Radix extract was daily given to the normal rats, control (bleomycin) and treated (bleomycin and Astragali Radix extract, 24.0 mg/10g body weight) rats for 14 days. After 14 days, we observed the change of total leukocyte count and percentage, IFN-gamma and IL-4 in BALF (Bronchoalveolar lavage fluid), and of semiquantitative histological index (SHI). Results: Compared to the control group, Astragali Radix decreased total leukocyte count (p<0.05), lymphocyte (p<0.05), neutrophil (no significance) percentage, SHI (p<0.05), IFN-gamma and IL-4 (p<0.05). Otherwise, macrophage percentage was increased (p<0.01). Conclusion: This study showed that Astragali Radix reduced the incidence of inflammatory cells and cytokines and prevented the fibrosis of tissue in bleomycin-induced lung fibrosis rats.

• The Journal of Internal Korean Medicine
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• v.26 no.1
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• pp.169-181
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• 2005

Background & Objective : Idiopathic Lung Fibrosis(IPF) is chronic fibrotic interstitial pneumonia. The pathogenesis is unclear. Fritillariae Rhizoma is the most commonly used antitussive and expectorant Oriental medicinal herb. The effects of Fritillariae Rhizoma on bleomycin-induced lung fibrosis is here evaluated. Material and Methods : Fritillariae Rhizoma extract was daily given to the normal rats, control(bleomycin) rats and treated(bleomycin and Fritillariae Rhizoma) rats at 9.0 mg per body weight 10g for 14 days. 14 days later, the change in Leukocyte count and percentages were observed, as well as IFN-gamma and 1L-4 in BALF, and the change in Semiqualitative histological index(SHI). Results : Compared to control rats, Fritillariae Rhizoma treated rats showed a lower leukocyte count(P<0.05) lymphocyte, neutrophil percentage, SHI(p<0.05), IFN-gamma and IL-4(p<0.05) in treated rats. Conversely, macrophage percentages went higher(p<0.05) in treated rats. Conclusion : This study supports a role for Fritillariae Rhizoma in reducing the maintaining inflammatory cells and cytokines in rats with bleomycin-induced lung fibrosis and in the reduction of fibrosis tissues. Further research is needed in order to develop an effective treatment for lung fibrosis.

• Tuberculosis and Respiratory Diseases
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• v.50 no.4
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• pp.504-509
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• 2001

There are numerous agents with potential toxic effects on the lung. In particular, cytotoxic drugs constitute the largest and most important group of agents associated with lung toxicity. Bleomycin is commonly used, either alone or in combination with other chemotherapeutic agents, in the treatment of squamous cell carcinoma(head and neck, esophagus, and genitourinary tract), lymphoma, and germ cell tumor. One of the therapeutic advantages of bleomycin is its minimal bone marrow toxicity. However, pulmonary toxicity is one of the most serious adverse side effects. Classically, pulmonary toxicity manifests as a diffuse interstitial process or less commonly as a hypersensitivity reaction. This pulmonary toxicity is generally considered to be dose related and can progress to a fatal fibrosis. It is also possible that bronchiolitis obliterans organizing pneumonia(BOOP) is another manifestation of bleomycin induced toxicity. Bleomycin induced BOOP is less common and has a favorable response to steroid therapy. Here we present a case that demonstrates a BOOP, secondary to a relatively small cumulative dose of bleomycin($225mg/m^2$), may be reversible.