Effect of Nilotinib on Bleomycin-Induced Acute Lung Injury and Pulmonary Fibrosis in Mice
Background: The tyrosine kinase inhibitor imatinib mesylate was developed as an inhibitor of the kinase activity of BCR-ABL. However, imatinib also has potent inhibitory activity against the platelet-derived growth factor receptor (PDGFR). Nilotinib is approved for treating patients with chronic mye...
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| creator | Rhee, Chin Kook Lee, Sang Haak Yoon, Hyung Kyu Kim, Seok Chan Lee, Sook Young Kwon, Soon Suk Kim, Young Kyoon Kim, Kwan Hyoung Kim, Tae Jung Kim, Jin Woo |
| description | Background: The tyrosine kinase inhibitor imatinib mesylate was developed as an inhibitor of the kinase activity of BCR-ABL. However, imatinib also has potent inhibitory activity against the platelet-derived growth factor receptor (PDGFR). Nilotinib is approved for treating patients with chronic myeloid leukemia showing resistance or intolerance to imatinib. Like imatinib, nilotinib selectively inhibits the tyrosine kinase activity of PDGFR. Objectives: We examined the effect of imatinib and nilotinib on acute lung injury and pulmonary fibrosis in a mouse model. Methods: Mice were treated by intratracheal instillation of bleomycin. Imatinib or nilotinib were administered by oral gavage. To study the early inflammatory and late fibrotic phases of lung injury, mice were sacrificed on days 3, 7, 14 and 21 after bleomycin instillation. Results: Histopathology showed that imatinib and nilotinib attenuated the extent of lung injury and fibrosis. The numbers of inflammatory cells and levels of IL-6, IL-1β and tumor necrosis factor-α were decreased in the imatinib and nilotinib groups on days 3 and 7. Imatinib and nilotinib therapy significantly reduced the levels of hydroxyproline on days 14 and 21, which was accompanied by decreased expression levels of transforming growth factor (TGF)-β1 and PDGFR-β. Imatinib and nilotinib also significantly reduced the expression levels of the genes for TGF-β1 and platelet-derived growth factor (PDGF). Imatinib and nilotinib treatment also significantly inhibited the PDGF-induced proliferation of lung fibroblasts in vitro. When imatinib or nilotinib was given 7 days after the instillation of bleomycin, only nilotinib attenuated pulmonary fibrosis. Conclusions: Imatinib and nilotinib attenuated bleomycin-induced acute lung injury and pulmonary fibrosis in mice. In a therapeutic model, nilotinib showed more potent antifibrotic effects than imatinib. |
| doi_str_mv | 10.1159/000327719 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7068797</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2463371921</sourcerecordid><originalsourceid>FETCH-LOGICAL-c518t-7c76c88563f7013cf25bf2cd355f31c99f1d5f5ae11b087cb6f1ef2dbc29b6613</originalsourceid><addsrcrecordid>eNpVkcFvFCEUxkmjadetB-_GkCYePIzlwTLApUltWt1kWz3owRNhGFhZZ6GFGZP-96K7rnp6Ie-X7_seH0IvgLwF4OqcEMKoEKCO0AwWlDWE8fYJmhFCeSMUgxP0rJQNIcClpMfohELLlaB0hr5ee-_siJPHd2FIY4ihwynid4NL20cbYrOM_WRdjy_tNDq8muIaL-Nmyo_YxB5_moZtiqa-bkKXUwkFh4hvg3Wn6Kk3Q3HP93OOvtxcf7760Kw-vl9eXa4ay0GOjbCitVLylnlBgFlPeeep7RnnnoFVykPPPTcOoCNS2K714DztO0tV17bA5uhip3s_dVvXWxfHbAZ9n8O2xtLJBP3_JoZvep1-aEFaKZSoAmd7gZweJldGvUlTjjWzlooquWC_Xd7sIFuPLNn5gwEQ_asEfSihsq_-TXQg__x6BV7vAVOsGXw20Ybyl1ssan_Vd45e7rjvJq9dPgB7n5_vEJgV</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>892984361</pqid></control><display><type>article</type><title>Effect of Nilotinib on Bleomycin-Induced Acute Lung Injury and Pulmonary Fibrosis in Mice</title><source>Karger Journals</source><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Rhee, Chin Kook ; Lee, Sang Haak ; Yoon, Hyung Kyu ; Kim, Seok Chan ; Lee, Sook Young ; Kwon, Soon Suk ; Kim, Young Kyoon ; Kim, Kwan Hyoung ; Kim, Tae Jung ; Kim, Jin Woo</creator><creatorcontrib>Rhee, Chin Kook ; Lee, Sang Haak ; Yoon, Hyung Kyu ; Kim, Seok Chan ; Lee, Sook Young ; Kwon, Soon Suk ; Kim, Young Kyoon ; Kim, Kwan Hyoung ; Kim, Tae Jung ; Kim, Jin Woo</creatorcontrib><description>Background: The tyrosine kinase inhibitor imatinib mesylate was developed as an inhibitor of the kinase activity of BCR-ABL. However, imatinib also has potent inhibitory activity against the platelet-derived growth factor receptor (PDGFR). Nilotinib is approved for treating patients with chronic myeloid leukemia showing resistance or intolerance to imatinib. Like imatinib, nilotinib selectively inhibits the tyrosine kinase activity of PDGFR. Objectives: We examined the effect of imatinib and nilotinib on acute lung injury and pulmonary fibrosis in a mouse model. Methods: Mice were treated by intratracheal instillation of bleomycin. Imatinib or nilotinib were administered by oral gavage. To study the early inflammatory and late fibrotic phases of lung injury, mice were sacrificed on days 3, 7, 14 and 21 after bleomycin instillation. Results: Histopathology showed that imatinib and nilotinib attenuated the extent of lung injury and fibrosis. The numbers of inflammatory cells and levels of IL-6, IL-1β and tumor necrosis factor-α were decreased in the imatinib and nilotinib groups on days 3 and 7. Imatinib and nilotinib therapy significantly reduced the levels of hydroxyproline on days 14 and 21, which was accompanied by decreased expression levels of transforming growth factor (TGF)-β1 and PDGFR-β. Imatinib and nilotinib also significantly reduced the expression levels of the genes for TGF-β1 and platelet-derived growth factor (PDGF). Imatinib and nilotinib treatment also significantly inhibited the PDGF-induced proliferation of lung fibroblasts in vitro. When imatinib or nilotinib was given 7 days after the instillation of bleomycin, only nilotinib attenuated pulmonary fibrosis. Conclusions: Imatinib and nilotinib attenuated bleomycin-induced acute lung injury and pulmonary fibrosis in mice. In a therapeutic model, nilotinib showed more potent antifibrotic effects than imatinib.</description><identifier>ISSN: 0025-7931</identifier><identifier>EISSN: 1423-0356</identifier><identifier>DOI: 10.1159/000327719</identifier><identifier>PMID: 21659722</identifier><identifier>CODEN: RESPBD</identifier><language>eng</language><publisher>Basel, Switzerland: Karger</publisher><subject>Acute Lung Injury - chemically induced ; Acute Lung Injury - drug therapy ; Acute Lung Injury - physiopathology ; Animals ; Antibiotics, Antineoplastic - adverse effects ; Basic Science Investigations ; Benzamides ; Biological and medical sciences ; Biomarkers, Tumor - metabolism ; Bleomycin - adverse effects ; Blotting, Western ; Gene Expression Regulation ; Imatinib Mesylate ; Inhibitor drugs ; Interleukin-1beta - metabolism ; Interleukin-6 - metabolism ; Kinases ; Lung diseases ; Male ; Medical sciences ; Mice ; Piperazines - pharmacology ; Pneumology ; Protein Kinase Inhibitors - pharmacology ; Protein-Tyrosine Kinases - antagonists & inhibitors ; Pulmonary Fibrosis - chemically induced ; Pulmonary Fibrosis - drug therapy ; Pulmonary Fibrosis - physiopathology ; Pyrimidines - pharmacology ; Real-Time Polymerase Chain Reaction ; Respiratory system : syndromes and miscellaneous diseases ; Rodents ; Time Factors ; Transforming Growth Factor beta1 - metabolism ; Tumor Necrosis Factor-alpha - metabolism</subject><ispartof>Respiration, 2011-01, Vol.82 (3), p.273-287</ispartof><rights>2011 S. Karger AG, Basel</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 S. Karger AG, Basel.</rights><rights>Copyright (c) 2011 S. Karger AG, Basel</rights><rights>Copyright © 2011 by S. Karger AG, Basel 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c518t-7c76c88563f7013cf25bf2cd355f31c99f1d5f5ae11b087cb6f1ef2dbc29b6613</citedby><cites>FETCH-LOGICAL-c518t-7c76c88563f7013cf25bf2cd355f31c99f1d5f5ae11b087cb6f1ef2dbc29b6613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,2423,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24435684$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21659722$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rhee, Chin Kook</creatorcontrib><creatorcontrib>Lee, Sang Haak</creatorcontrib><creatorcontrib>Yoon, Hyung Kyu</creatorcontrib><creatorcontrib>Kim, Seok Chan</creatorcontrib><creatorcontrib>Lee, Sook Young</creatorcontrib><creatorcontrib>Kwon, Soon Suk</creatorcontrib><creatorcontrib>Kim, Young Kyoon</creatorcontrib><creatorcontrib>Kim, Kwan Hyoung</creatorcontrib><creatorcontrib>Kim, Tae Jung</creatorcontrib><creatorcontrib>Kim, Jin Woo</creatorcontrib><title>Effect of Nilotinib on Bleomycin-Induced Acute Lung Injury and Pulmonary Fibrosis in Mice</title><title>Respiration</title><addtitle>Respiration</addtitle><description>Background: The tyrosine kinase inhibitor imatinib mesylate was developed as an inhibitor of the kinase activity of BCR-ABL. However, imatinib also has potent inhibitory activity against the platelet-derived growth factor receptor (PDGFR). Nilotinib is approved for treating patients with chronic myeloid leukemia showing resistance or intolerance to imatinib. Like imatinib, nilotinib selectively inhibits the tyrosine kinase activity of PDGFR. Objectives: We examined the effect of imatinib and nilotinib on acute lung injury and pulmonary fibrosis in a mouse model. Methods: Mice were treated by intratracheal instillation of bleomycin. Imatinib or nilotinib were administered by oral gavage. To study the early inflammatory and late fibrotic phases of lung injury, mice were sacrificed on days 3, 7, 14 and 21 after bleomycin instillation. Results: Histopathology showed that imatinib and nilotinib attenuated the extent of lung injury and fibrosis. The numbers of inflammatory cells and levels of IL-6, IL-1β and tumor necrosis factor-α were decreased in the imatinib and nilotinib groups on days 3 and 7. Imatinib and nilotinib therapy significantly reduced the levels of hydroxyproline on days 14 and 21, which was accompanied by decreased expression levels of transforming growth factor (TGF)-β1 and PDGFR-β. Imatinib and nilotinib also significantly reduced the expression levels of the genes for TGF-β1 and platelet-derived growth factor (PDGF). Imatinib and nilotinib treatment also significantly inhibited the PDGF-induced proliferation of lung fibroblasts in vitro. When imatinib or nilotinib was given 7 days after the instillation of bleomycin, only nilotinib attenuated pulmonary fibrosis. Conclusions: Imatinib and nilotinib attenuated bleomycin-induced acute lung injury and pulmonary fibrosis in mice. In a therapeutic model, nilotinib showed more potent antifibrotic effects than imatinib.</description><subject>Acute Lung Injury - chemically induced</subject><subject>Acute Lung Injury - drug therapy</subject><subject>Acute Lung Injury - physiopathology</subject><subject>Animals</subject><subject>Antibiotics, Antineoplastic - adverse effects</subject><subject>Basic Science Investigations</subject><subject>Benzamides</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Bleomycin - adverse effects</subject><subject>Blotting, Western</subject><subject>Gene Expression Regulation</subject><subject>Imatinib Mesylate</subject><subject>Inhibitor drugs</subject><subject>Interleukin-1beta - metabolism</subject><subject>Interleukin-6 - metabolism</subject><subject>Kinases</subject><subject>Lung diseases</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Piperazines - pharmacology</subject><subject>Pneumology</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Protein-Tyrosine Kinases - antagonists & inhibitors</subject><subject>Pulmonary Fibrosis - chemically induced</subject><subject>Pulmonary Fibrosis - drug therapy</subject><subject>Pulmonary Fibrosis - physiopathology</subject><subject>Pyrimidines - pharmacology</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Respiratory system : syndromes and miscellaneous diseases</subject><subject>Rodents</subject><subject>Time Factors</subject><subject>Transforming Growth Factor beta1 - metabolism</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><issn>0025-7931</issn><issn>1423-0356</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpVkcFvFCEUxkmjadetB-_GkCYePIzlwTLApUltWt1kWz3owRNhGFhZZ6GFGZP-96K7rnp6Ie-X7_seH0IvgLwF4OqcEMKoEKCO0AwWlDWE8fYJmhFCeSMUgxP0rJQNIcClpMfohELLlaB0hr5ee-_siJPHd2FIY4ihwynid4NL20cbYrOM_WRdjy_tNDq8muIaL-Nmyo_YxB5_moZtiqa-bkKXUwkFh4hvg3Wn6Kk3Q3HP93OOvtxcf7760Kw-vl9eXa4ay0GOjbCitVLylnlBgFlPeeep7RnnnoFVykPPPTcOoCNS2K714DztO0tV17bA5uhip3s_dVvXWxfHbAZ9n8O2xtLJBP3_JoZvep1-aEFaKZSoAmd7gZweJldGvUlTjjWzlooquWC_Xd7sIFuPLNn5gwEQ_asEfSihsq_-TXQg__x6BV7vAVOsGXw20Ybyl1ssan_Vd45e7rjvJq9dPgB7n5_vEJgV</recordid><startdate>20110101</startdate><enddate>20110101</enddate><creator>Rhee, Chin Kook</creator><creator>Lee, Sang Haak</creator><creator>Yoon, Hyung Kyu</creator><creator>Kim, Seok Chan</creator><creator>Lee, Sook Young</creator><creator>Kwon, Soon Suk</creator><creator>Kim, Young Kyoon</creator><creator>Kim, Kwan Hyoung</creator><creator>Kim, Tae Jung</creator><creator>Kim, Jin Woo</creator><general>Karger</general><general>S. 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chemically induced</topic><topic>Acute Lung Injury - drug therapy</topic><topic>Acute Lung Injury - physiopathology</topic><topic>Animals</topic><topic>Antibiotics, Antineoplastic - adverse effects</topic><topic>Basic Science Investigations</topic><topic>Benzamides</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Bleomycin - adverse effects</topic><topic>Blotting, Western</topic><topic>Gene Expression Regulation</topic><topic>Imatinib Mesylate</topic><topic>Inhibitor drugs</topic><topic>Interleukin-1beta - metabolism</topic><topic>Interleukin-6 - metabolism</topic><topic>Kinases</topic><topic>Lung diseases</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Piperazines - pharmacology</topic><topic>Pneumology</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Protein-Tyrosine Kinases - antagonists & inhibitors</topic><topic>Pulmonary Fibrosis - chemically induced</topic><topic>Pulmonary Fibrosis - drug therapy</topic><topic>Pulmonary Fibrosis - physiopathology</topic><topic>Pyrimidines - pharmacology</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Respiratory system : syndromes and miscellaneous diseases</topic><topic>Rodents</topic><topic>Time Factors</topic><topic>Transforming Growth Factor beta1 - metabolism</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rhee, Chin Kook</creatorcontrib><creatorcontrib>Lee, Sang Haak</creatorcontrib><creatorcontrib>Yoon, Hyung Kyu</creatorcontrib><creatorcontrib>Kim, Seok Chan</creatorcontrib><creatorcontrib>Lee, Sook Young</creatorcontrib><creatorcontrib>Kwon, Soon Suk</creatorcontrib><creatorcontrib>Kim, Young Kyoon</creatorcontrib><creatorcontrib>Kim, Kwan Hyoung</creatorcontrib><creatorcontrib>Kim, Tae Jung</creatorcontrib><creatorcontrib>Kim, Jin Woo</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Career & Technical Education Database</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Respiration</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rhee, Chin Kook</au><au>Lee, Sang Haak</au><au>Yoon, Hyung Kyu</au><au>Kim, Seok Chan</au><au>Lee, Sook Young</au><au>Kwon, Soon Suk</au><au>Kim, Young Kyoon</au><au>Kim, Kwan Hyoung</au><au>Kim, Tae Jung</au><au>Kim, Jin Woo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of Nilotinib on Bleomycin-Induced Acute Lung Injury and Pulmonary Fibrosis in Mice</atitle><jtitle>Respiration</jtitle><addtitle>Respiration</addtitle><date>2011-01-01</date><risdate>2011</risdate><volume>82</volume><issue>3</issue><spage>273</spage><epage>287</epage><pages>273-287</pages><issn>0025-7931</issn><eissn>1423-0356</eissn><coden>RESPBD</coden><abstract>Background: The tyrosine kinase inhibitor imatinib mesylate was developed as an inhibitor of the kinase activity of BCR-ABL. However, imatinib also has potent inhibitory activity against the platelet-derived growth factor receptor (PDGFR). Nilotinib is approved for treating patients with chronic myeloid leukemia showing resistance or intolerance to imatinib. Like imatinib, nilotinib selectively inhibits the tyrosine kinase activity of PDGFR. Objectives: We examined the effect of imatinib and nilotinib on acute lung injury and pulmonary fibrosis in a mouse model. Methods: Mice were treated by intratracheal instillation of bleomycin. Imatinib or nilotinib were administered by oral gavage. To study the early inflammatory and late fibrotic phases of lung injury, mice were sacrificed on days 3, 7, 14 and 21 after bleomycin instillation. Results: Histopathology showed that imatinib and nilotinib attenuated the extent of lung injury and fibrosis. The numbers of inflammatory cells and levels of IL-6, IL-1β and tumor necrosis factor-α were decreased in the imatinib and nilotinib groups on days 3 and 7. Imatinib and nilotinib therapy significantly reduced the levels of hydroxyproline on days 14 and 21, which was accompanied by decreased expression levels of transforming growth factor (TGF)-β1 and PDGFR-β. Imatinib and nilotinib also significantly reduced the expression levels of the genes for TGF-β1 and platelet-derived growth factor (PDGF). Imatinib and nilotinib treatment also significantly inhibited the PDGF-induced proliferation of lung fibroblasts in vitro. When imatinib or nilotinib was given 7 days after the instillation of bleomycin, only nilotinib attenuated pulmonary fibrosis. Conclusions: Imatinib and nilotinib attenuated bleomycin-induced acute lung injury and pulmonary fibrosis in mice. In a therapeutic model, nilotinib showed more potent antifibrotic effects than imatinib.</abstract><cop>Basel, Switzerland</cop><pub>Karger</pub><pmid>21659722</pmid><doi>10.1159/000327719</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| source | Karger Journals; MEDLINE; Alma/SFX Local Collection |
| subjects | Acute Lung Injury - chemically induced Acute Lung Injury - drug therapy Acute Lung Injury - physiopathology Animals Antibiotics, Antineoplastic - adverse effects Basic Science Investigations Benzamides Biological and medical sciences Biomarkers, Tumor - metabolism Bleomycin - adverse effects Blotting, Western Gene Expression Regulation Imatinib Mesylate Inhibitor drugs Interleukin-1beta - metabolism Interleukin-6 - metabolism Kinases Lung diseases Male Medical sciences Mice Piperazines - pharmacology Pneumology Protein Kinase Inhibitors - pharmacology Protein-Tyrosine Kinases - antagonists & inhibitors Pulmonary Fibrosis - chemically induced Pulmonary Fibrosis - drug therapy Pulmonary Fibrosis - physiopathology Pyrimidines - pharmacology Real-Time Polymerase Chain Reaction Respiratory system : syndromes and miscellaneous diseases Rodents Time Factors Transforming Growth Factor beta1 - metabolism Tumor Necrosis Factor-alpha - metabolism |
| title | Effect of Nilotinib on Bleomycin-Induced Acute Lung Injury and Pulmonary Fibrosis in Mice |
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