Quercetin liposomes protect against radiation-induced pulmonary injury in a murine model
Identifieur interne : 000178 ( Pmc/Checkpoint ); précédent : 000177; suivant : 000179Quercetin liposomes protect against radiation-induced pulmonary injury in a murine model
Auteurs : Hao Liu ; Jian-Xing Xue ; Xing Li ; Rui Ao ; You LuSource :
- Oncology Letters [ 1792-1074 ] ; 2013.
Abstract
In the present study, the hypothesis that quercetin liposomes are able to effectively protect against radiation-induced pulmonary injury in a murine model was tested. C57BL/6J mice receiving whole-thorax radiotherapy (16 Gy) were randomly divided into three groups: control, radiation therapy plus saline (RT+NS) and RT plus quercetin (RT+QU). At 1, 4, 8 and 24 weeks post-irradiation, lung injury was assessed by measuring oxidative damage and the extent of acute pneumonitis and late fibrosis. In the lung tissues from the RT+NS group, the malondialdehyde (MDA) levels were significantly elevated and superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities were significantly reduced; the total cell counts and inflammatory cell proportions in the bronchoalveolar lavage fluid (BALF), plasma tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 concentrations and the hydroxyproline (HP) content were significantly increased. Quercetin liposome administration significantly reduced the MDA content and increased SOD and GSH-PX activities in the lung tissues, and reduced the total cell counts and inflammatory cell proportions in the BALF, plasma TNF-α and TGF-β1 concentrations and the HP content in the lung tissues. A histological examination revealed suppression of the inflammatory response and reduced TGF-β1 expression and fibrosis scores. Radiation-induced oxidative damage ranged from pneumonitis to lung fibrosis. Quercetin liposomes were shown to protect against radiation-induced acute pneumonitis and late fibrosis, potentially by reducing oxidative damage.
Url:
DOI: 10.3892/ol.2013.1365
PubMed: 24137346
PubMed Central: 3789113
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Quercetin liposomes protect against radiation-induced pulmonary injury in a murine model</title><author><name sortKey="Liu, Hao" sort="Liu, Hao" uniqKey="Liu H" first="Hao" last="Liu">Hao Liu</name><affiliation><nlm:aff id="af1-ol-06-02-0453">Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041,<country>P.R. China</country>;</nlm:aff><wicri:noCountry code="nlm country">P.R. China</wicri:noCountry></affiliation><affiliation><nlm:aff id="af2-ol-06-02-0453">Department of Oncology, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, Chengdu, Sichuan 610041,<country>P.R. China</country></nlm:aff><wicri:noCountry code="nlm country">P.R. China</wicri:noCountry></affiliation></author><author><name sortKey="Xue, Jian Xing" sort="Xue, Jian Xing" uniqKey="Xue J" first="Jian-Xing" last="Xue">Jian-Xing Xue</name><affiliation><nlm:aff id="af1-ol-06-02-0453">Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041,<country>P.R. China</country>;</nlm:aff><wicri:noCountry code="nlm country">P.R. China</wicri:noCountry></affiliation></author><author><name sortKey="Li, Xing" sort="Li, Xing" uniqKey="Li X" first="Xing" last="Li">Xing Li</name><affiliation><nlm:aff id="af1-ol-06-02-0453">Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041,<country>P.R. China</country>;</nlm:aff><wicri:noCountry code="nlm country">P.R. China</wicri:noCountry></affiliation></author><author><name sortKey="Ao, Rui" sort="Ao, Rui" uniqKey="Ao R" first="Rui" last="Ao">Rui Ao</name><affiliation><nlm:aff id="af2-ol-06-02-0453">Department of Oncology, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, Chengdu, Sichuan 610041,<country>P.R. China</country></nlm:aff><wicri:noCountry code="nlm country">P.R. China</wicri:noCountry></affiliation></author><author><name sortKey="Lu, You" sort="Lu, You" uniqKey="Lu Y" first="You" last="Lu">You Lu</name><affiliation><nlm:aff id="af1-ol-06-02-0453">Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041,<country>P.R. China</country>;</nlm:aff><wicri:noCountry code="nlm country">P.R. China</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24137346</idno><idno type="pmc">3789113</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3789113</idno><idno type="RBID">PMC:3789113</idno><idno type="doi">10.3892/ol.2013.1365</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000442</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000442</idno><idno type="wicri:Area/Pmc/Curation">000441</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000441</idno><idno type="wicri:Area/Pmc/Checkpoint">000178</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000178</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Quercetin liposomes protect against radiation-induced pulmonary injury in a murine model</title><author><name sortKey="Liu, Hao" sort="Liu, Hao" uniqKey="Liu H" first="Hao" last="Liu">Hao Liu</name><affiliation><nlm:aff id="af1-ol-06-02-0453">Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041,<country>P.R. China</country>;</nlm:aff><wicri:noCountry code="nlm country">P.R. China</wicri:noCountry></affiliation><affiliation><nlm:aff id="af2-ol-06-02-0453">Department of Oncology, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, Chengdu, Sichuan 610041,<country>P.R. China</country></nlm:aff><wicri:noCountry code="nlm country">P.R. China</wicri:noCountry></affiliation></author><author><name sortKey="Xue, Jian Xing" sort="Xue, Jian Xing" uniqKey="Xue J" first="Jian-Xing" last="Xue">Jian-Xing Xue</name><affiliation><nlm:aff id="af1-ol-06-02-0453">Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041,<country>P.R. China</country>;</nlm:aff><wicri:noCountry code="nlm country">P.R. China</wicri:noCountry></affiliation></author><author><name sortKey="Li, Xing" sort="Li, Xing" uniqKey="Li X" first="Xing" last="Li">Xing Li</name><affiliation><nlm:aff id="af1-ol-06-02-0453">Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041,<country>P.R. China</country>;</nlm:aff><wicri:noCountry code="nlm country">P.R. China</wicri:noCountry></affiliation></author><author><name sortKey="Ao, Rui" sort="Ao, Rui" uniqKey="Ao R" first="Rui" last="Ao">Rui Ao</name><affiliation><nlm:aff id="af2-ol-06-02-0453">Department of Oncology, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, Chengdu, Sichuan 610041,<country>P.R. China</country></nlm:aff><wicri:noCountry code="nlm country">P.R. China</wicri:noCountry></affiliation></author><author><name sortKey="Lu, You" sort="Lu, You" uniqKey="Lu Y" first="You" last="Lu">You Lu</name><affiliation><nlm:aff id="af1-ol-06-02-0453">Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041,<country>P.R. China</country>;</nlm:aff><wicri:noCountry code="nlm country">P.R. China</wicri:noCountry></affiliation></author></analytic><series><title level="j">Oncology Letters</title><idno type="ISSN">1792-1074</idno><idno type="eISSN">1792-1082</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>In the present study, the hypothesis that quercetin liposomes are able to effectively protect against radiation-induced pulmonary injury in a murine model was tested. C57BL/6J mice receiving whole-thorax radiotherapy (16 Gy) were randomly divided into three groups: control, radiation therapy plus saline (RT+NS) and RT plus quercetin (RT+QU). At 1, 4, 8 and 24 weeks post-irradiation, lung injury was assessed by measuring oxidative damage and the extent of acute pneumonitis and late fibrosis. In the lung tissues from the RT+NS group, the malondialdehyde (MDA) levels were significantly elevated and superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities were significantly reduced; the total cell counts and inflammatory cell proportions in the bronchoalveolar lavage fluid (BALF), plasma tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 concentrations and the hydroxyproline (HP) content were significantly increased. Quercetin liposome administration significantly reduced the MDA content and increased SOD and GSH-PX activities in the lung tissues, and reduced the total cell counts and inflammatory cell proportions in the BALF, plasma TNF-α and TGF-β1 concentrations and the HP content in the lung tissues. A histological examination revealed suppression of the inflammatory response and reduced TGF-β1 expression and fibrosis scores. Radiation-induced oxidative damage ranged from pneumonitis to lung fibrosis. Quercetin liposomes were shown to protect against radiation-induced acute pneumonitis and late fibrosis, potentially by reducing oxidative damage.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Stone, Hb" uniqKey="Stone H">HB Stone</name></author><author><name sortKey="Coleman, Cn" uniqKey="Coleman C">CN Coleman</name></author><author><name sortKey="Anscher, Ms" uniqKey="Anscher M">MS Anscher</name></author><author><name sortKey="Mcbride, Wh" uniqKey="Mcbride W">WH McBride</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tsoutsou, Pg" uniqKey="Tsoutsou P">PG Tsoutsou</name></author><author><name sortKey="Koukourakis, Mi" uniqKey="Koukourakis M">MI Koukourakis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, W" uniqKey="Zhao W">W Zhao</name></author><author><name sortKey="Robbins, Me" uniqKey="Robbins M">ME 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Oncol Lett</journal-id><journal-id journal-id-type="iso-abbrev">Oncol Lett</journal-id><journal-id journal-id-type="publisher-id">OL</journal-id><journal-title-group><journal-title>Oncology Letters</journal-title></journal-title-group><issn pub-type="ppub">1792-1074</issn><issn pub-type="epub">1792-1082</issn><publisher><publisher-name>D.A. Spandidos</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24137346</article-id><article-id pub-id-type="pmc">3789113</article-id><article-id pub-id-type="doi">10.3892/ol.2013.1365</article-id><article-id pub-id-type="publisher-id">ol-06-02-0453</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group></article-categories><title-group><article-title>Quercetin liposomes protect against radiation-induced pulmonary injury in a murine model</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>LIU</surname><given-names>HAO</given-names></name><xref ref-type="aff" rid="af1-ol-06-02-0453"><sup>1</sup></xref><xref ref-type="aff" rid="af2-ol-06-02-0453"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>XUE</surname><given-names>JIAN-XING</given-names></name><xref ref-type="aff" rid="af1-ol-06-02-0453"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>LI</surname><given-names>XING</given-names></name><xref ref-type="aff" rid="af1-ol-06-02-0453"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>AO</surname><given-names>RUI</given-names></name><xref ref-type="aff" rid="af2-ol-06-02-0453"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>LU</surname><given-names>YOU</given-names></name><xref ref-type="aff" rid="af1-ol-06-02-0453"><sup>1</sup></xref><xref rid="c1-ol-06-02-0453" ref-type="corresp"></xref></contrib></contrib-group><aff id="af1-ol-06-02-0453"><label>1</label>Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041,<country>P.R. China</country>;</aff><aff id="af2-ol-06-02-0453"><label>2</label>Department of Oncology, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, Chengdu, Sichuan 610041,<country>P.R. China</country></aff><author-notes><corresp id="c1-ol-06-02-0453">Correspondence to: Professor You Lu, Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China School of Medicine, Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan 610041, P.R. China, E-mail: <email>radyoulu@hotmail.com</email></corresp></author-notes><pub-date pub-type="ppub"><month>8</month><year>2013</year></pub-date><pub-date pub-type="epub"><day>29</day><month>5</month><year>2013</year></pub-date><pub-date pub-type="pmc-release"><day>29</day><month>5</month><year>2013</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>6</volume><issue>2</issue><fpage>453</fpage><lpage>459</lpage><history><date date-type="received"><day>20</day><month>1</month><year>2013</year></date><date date-type="accepted"><day>17</day><month>5</month><year>2013</year></date></history><permissions><copyright-statement>Copyright © 2013, Spandidos Publications</copyright-statement><copyright-year>2013</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/3.0"><license-p>This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.</license-p></license></permissions><abstract><p>In the present study, the hypothesis that quercetin liposomes are able to effectively protect against radiation-induced pulmonary injury in a murine model was tested. C57BL/6J mice receiving whole-thorax radiotherapy (16 Gy) were randomly divided into three groups: control, radiation therapy plus saline (RT+NS) and RT plus quercetin (RT+QU). At 1, 4, 8 and 24 weeks post-irradiation, lung injury was assessed by measuring oxidative damage and the extent of acute pneumonitis and late fibrosis. In the lung tissues from the RT+NS group, the malondialdehyde (MDA) levels were significantly elevated and superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities were significantly reduced; the total cell counts and inflammatory cell proportions in the bronchoalveolar lavage fluid (BALF), plasma tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 concentrations and the hydroxyproline (HP) content were significantly increased. Quercetin liposome administration significantly reduced the MDA content and increased SOD and GSH-PX activities in the lung tissues, and reduced the total cell counts and inflammatory cell proportions in the BALF, plasma TNF-α and TGF-β1 concentrations and the HP content in the lung tissues. A histological examination revealed suppression of the inflammatory response and reduced TGF-β1 expression and fibrosis scores. Radiation-induced oxidative damage ranged from pneumonitis to lung fibrosis. Quercetin liposomes were shown to protect against radiation-induced acute pneumonitis and late fibrosis, potentially by reducing oxidative damage.</p></abstract><kwd-group><kwd>radiation pneumonitis</kwd><kwd>quercetin</kwd><kwd>oxidative stress</kwd><kwd>liposome</kwd></kwd-group></article-meta></front><floats-group><fig id="f1-ol-06-02-0453" orientation="portrait" position="float"><label>Figure 1.</label><caption><p>Measurement of (A) malondialdehyde (MDA) content and (B) glutathione peroxidase (GSH-PX) and (C) superoxide dismutase (SOD) activities in lung homogenates from experimental groups at 1, 4, 8 and 24 weeks post-irradiation. Values are expressed as the mean ± standard deviation (SD). <sup>**</sup>P<0.01, <sup>*</sup>P<0.05. Con, control; RT, radiotherapy; NS, saline; Qu, quercetin liposome.</p></caption><graphic xlink:href="OL-06-02-0453-g00"></graphic></fig><fig id="f2-ol-06-02-0453" orientation="portrait" position="float"><label>Figure 2.</label><caption><p>(A) Representative image of hematoxylin and eosin (HE)-stained cells in bronchoalveolar lavage fluid (BALF). Epithelial cells and macrophages were observed in samples from the control (CON) group. Significant increases in neutrophils showing nuclear lobulation and deeply stained small lymphocytes were observed in samples from the radiotherapy plus saline (RT+NS) group. The numbers of neutrophils and lymphocytes were noticeably reduced in samples from the radiotherapy plus quercetin liposome (RT+QU) group. Magnification, ×400. (B) Total cell counts and (C) percentages of inflammatory cells in BALF. <sup>**</sup>P<0.01, <sup>*</sup>P<0.05.</p></caption><graphic xlink:href="OL-06-02-0453-g01"></graphic></fig><fig id="f3-ol-06-02-0453" orientation="portrait" position="float"><label>Figure 3.</label><caption><p>Dynamic changes in (A) tumor necrosis factor (TNF)-α and (B) transforming growth factor (TGF)-β1 concentrations in plasma from 1–24 weeks post-irradiation in the experimental groups. n=4–5 mice per group at 1, 4, 8 and 24 weeks. <sup>**</sup>P<0.01, <sup>*</sup>P<0.05. Con, control; RT, radiotherapy; NS, saline; Qu, quercetin liposome.</p></caption><graphic xlink:href="OL-06-02-0453-g02"></graphic></fig><fig id="f4-ol-06-02-0453" orientation="portrait" position="float"><label>Figure 4.</label><caption><p>Photomicrographs of hematoxylin and eosin (HE)-stained lung sections from the control (CON), radiotherapy plus saline (RT+NS) and radiotherapy plus quercetin liposome (RT+QU) groups at various timepoints after irradiation. Magnification, ×400.</p></caption><graphic xlink:href="OL-06-02-0453-g03"></graphic></fig><fig id="f5-ol-06-02-0453" orientation="portrait" position="float"><label>Figure 5.</label><caption><p>(A) Masson’s trichrome staining of lung tissue sections, with collagen fibers dyed blue. Magnification, ×400. (B) Lung fibrosis scores at 24 weeks after irradiation. Con, control; RT, radiotherapy; NS, saline; Qu, quercetin liposome.</p></caption><graphic xlink:href="OL-06-02-0453-g04"></graphic></fig><fig id="f6-ol-06-02-0453" orientation="portrait" position="float"><label>Figure 6.</label><caption><p>(A) Immunocytochemical staining with anti-transforming growth factor (TGF)-β1, with the cytoplasm of cells expressing TGF-β1 stained brown. Magnification, ×400 (B) Number of stained cells was counted within each field. Values are expressed as the mean ± standard deviation (SD). <sup>**</sup>P<0.01, <sup>*</sup>P<0.05. Con, control; RT, radiotherapy; NS, saline; Qu, quercetin liposome.</p></caption><graphic xlink:href="OL-06-02-0453-g05"></graphic></fig><fig id="f7-ol-06-02-0453" orientation="portrait" position="float"><label>Figure 7.</label><caption><p>Collagen deposition was estimated by determining the hydroxyproline (HP) content of lung tissue in 4–5 mice per group at 1, 4, 8 and 24 weeks post-irradiation. <sup>**</sup>P<0.01, <sup>*</sup>P<0.05. Con, control; RT, radiotherapy; NS, saline; Qu, quercetin liposome.</p></caption><graphic xlink:href="OL-06-02-0453-g06"></graphic></fig></floats-group></pmc><affiliations><list></list><tree><noCountry><name sortKey="Ao, Rui" sort="Ao, Rui" uniqKey="Ao R" first="Rui" last="Ao">Rui Ao</name><name sortKey="Li, Xing" sort="Li, Xing" uniqKey="Li X" first="Xing" last="Li">Xing Li</name><name sortKey="Liu, Hao" sort="Liu, Hao" uniqKey="Liu H" first="Hao" last="Liu">Hao Liu</name><name sortKey="Lu, You" sort="Lu, You" uniqKey="Lu Y" first="You" last="Lu">You Lu</name><name sortKey="Xue, Jian Xing" sort="Xue, Jian Xing" uniqKey="Xue J" first="Jian-Xing" last="Xue">Jian-Xing Xue</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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