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Dose-response Effects of Bleomycin on Inflammation and Pulmonary Fibrosis in Mice
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 bleom...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Society of Toxicology
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834487/ https://www.ncbi.nlm.nih.gov/pubmed/24278527 http://dx.doi.org/10.5487/TR.2010.26.3.217 |
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author | Kim, Soo Nam Lee, Jinsoo Yang, Hyo-Seon Cho, Jae-Woo Kwon, Soonjin Kim, Young-Beom Her, Jeong-Doo Cho, Kyu-Hyuk Song, Chang-Woo Lee, Kyuhong |
author_facet | Kim, Soo Nam Lee, Jinsoo Yang, Hyo-Seon Cho, Jae-Woo Kwon, Soonjin Kim, Young-Beom Her, Jeong-Doo Cho, Kyu-Hyuk Song, Chang-Woo Lee, Kyuhong |
author_sort | Kim, Soo Nam |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3834487 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Korean Society of Toxicology |
record_format | MEDLINE/PubMed |
spelling | pubmed-38344872013-11-25 Dose-response Effects of Bleomycin on Inflammation and Pulmonary Fibrosis in Mice Kim, Soo Nam Lee, Jinsoo Yang, Hyo-Seon Cho, Jae-Woo Kwon, Soonjin Kim, Young-Beom Her, Jeong-Doo Cho, Kyu-Hyuk Song, Chang-Woo Lee, Kyuhong Toxicol Res Article 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 Korean Society of Toxicology 2010-09 /pmc/articles/PMC3834487/ /pubmed/24278527 http://dx.doi.org/10.5487/TR.2010.26.3.217 Text en Copyright ©2010, The Korean Society of Toxicology |
spellingShingle | Article Kim, Soo Nam Lee, Jinsoo Yang, Hyo-Seon Cho, Jae-Woo Kwon, Soonjin Kim, Young-Beom Her, Jeong-Doo Cho, Kyu-Hyuk Song, Chang-Woo Lee, Kyuhong Dose-response Effects of Bleomycin on Inflammation and Pulmonary Fibrosis in Mice |
title | Dose-response Effects of Bleomycin on Inflammation and Pulmonary Fibrosis in Mice |
title_full | Dose-response Effects of Bleomycin on Inflammation and Pulmonary Fibrosis in Mice |
title_fullStr | Dose-response Effects of Bleomycin on Inflammation and Pulmonary Fibrosis in Mice |
title_full_unstemmed | Dose-response Effects of Bleomycin on Inflammation and Pulmonary Fibrosis in Mice |
title_short | Dose-response Effects of Bleomycin on Inflammation and Pulmonary Fibrosis in Mice |
title_sort | dose-response effects of bleomycin on inflammation and pulmonary fibrosis in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834487/ https://www.ncbi.nlm.nih.gov/pubmed/24278527 http://dx.doi.org/10.5487/TR.2010.26.3.217 |
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