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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Mitigation of Radiation-Induced Lung Injury with EUK-207 and Genistein: Effects in Adolescent Rats</title><author><name sortKey="Mahmood, J" sort="Mahmood, J" uniqKey="Mahmood J" first="J." last="Mahmood">J. Mahmood</name><affiliation><nlm:aff id="A1">Ontario Cancer Institute/Princess Margaret Cancer Center, University Health Network, and The Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Radiation Medicine Program, STTARR Innovation Centre, Princess Margaret Hospital, Toronto, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Jelveh, S" sort="Jelveh, S" uniqKey="Jelveh S" first="S." last="Jelveh">S. Jelveh</name><affiliation><nlm:aff id="A1">Ontario Cancer Institute/Princess Margaret Cancer Center, University Health Network, and The Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Radiation Medicine Program, STTARR Innovation Centre, Princess Margaret Hospital, Toronto, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Zaidi, A" sort="Zaidi, A" uniqKey="Zaidi A" first="A." last="Zaidi">A. Zaidi</name><affiliation><nlm:aff id="A1">Ontario Cancer Institute/Princess Margaret Cancer Center, University Health Network, and The Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Doctrow, S R" sort="Doctrow, S R" uniqKey="Doctrow S" first="S. R." last="Doctrow">S. R. Doctrow</name><affiliation><nlm:aff id="A3">Pulmonary Center, Department of Medicine, Boston University, Boston, Massachusetts</nlm:aff></affiliation></author><author><name sortKey="Hill, R P" sort="Hill, R P" uniqKey="Hill R" first="R. P." last="Hill">R. P. Hill</name><affiliation><nlm:aff id="A4">Departments of Medical Biophysics and Radiation Oncology, University of Toronto, Toronto, Ontario, Canada</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23237541</idno><idno type="pmc">3617812</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617812</idno><idno type="RBID">PMC:3617812</idno><idno type="doi">10.1667/RR2954.1</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000726</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000726</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Mitigation of Radiation-Induced Lung Injury with EUK-207 and Genistein: Effects in Adolescent Rats</title><author><name sortKey="Mahmood, J" sort="Mahmood, J" uniqKey="Mahmood J" first="J." last="Mahmood">J. Mahmood</name><affiliation><nlm:aff id="A1">Ontario Cancer Institute/Princess Margaret Cancer Center, University Health Network, and The Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Radiation Medicine Program, STTARR Innovation Centre, Princess Margaret Hospital, Toronto, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Jelveh, S" sort="Jelveh, S" uniqKey="Jelveh S" first="S." last="Jelveh">S. Jelveh</name><affiliation><nlm:aff id="A1">Ontario Cancer Institute/Princess Margaret Cancer Center, University Health Network, and The Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Radiation Medicine Program, STTARR Innovation Centre, Princess Margaret Hospital, Toronto, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Zaidi, A" sort="Zaidi, A" uniqKey="Zaidi A" first="A." last="Zaidi">A. Zaidi</name><affiliation><nlm:aff id="A1">Ontario Cancer Institute/Princess Margaret Cancer Center, University Health Network, and The Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada</nlm:aff></affiliation></author><author><name sortKey="Doctrow, S R" sort="Doctrow, S R" uniqKey="Doctrow S" first="S. R." last="Doctrow">S. R. Doctrow</name><affiliation><nlm:aff id="A3">Pulmonary Center, Department of Medicine, Boston University, Boston, Massachusetts</nlm:aff></affiliation></author><author><name sortKey="Hill, R P" sort="Hill, R P" uniqKey="Hill R" first="R. P." last="Hill">R. P. Hill</name><affiliation><nlm:aff id="A4">Departments of Medical Biophysics and Radiation Oncology, University of Toronto, Toronto, Ontario, Canada</nlm:aff></affiliation></author></analytic><series><title level="j">Radiation research</title><idno type="ISSN">0033-7587</idno><idno type="eISSN">1938-5404</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Exposure of civilian populations to radiation due to accident, war or terrorist act is an increasing concern. The lung is one of the more radiosensitive organs that may be affected in people receiving partial-body irradiation and radiation injury in lung is thought to be associated with the development of a prolonged inflammatory response. Here we examined how effectively damage to the lung can be mitigated by administration of drugs initiated at different times after radiation exposure and examined response in adolescent animals for comparison with the young adult animals that we had studied previously. We studied the mitigation efficacy of the isoflavone genistein (50 mg/kg) and the salen-Mn superoxide dismutase-catalase mimetic EUK-207 (8 mg/kg), both of which have been reported to scavenge reactive oxygen species and reduce activity of the NFkB pathway. The drugs were given by subcutaneous injection to 6- to 7-week-old Fisher rats daily starting either immediately or 2 weeks after irradiation with 12 Gy to the whole thorax. The treatment was stopped at 28 weeks post irradiation and the animals were assessed for levels of inflammatory cytokines, activated macrophages, oxidative damage and fibrosis at 48 weeks post irradiation. We demonstrated that both genistein and EUK-207 delayed and suppressed the increased breathing rate associated with pneumonitis. These agents also reduced levels of oxidative damage (50–100%), levels of TGF-β1 expression (75–100%), activated macrophages (20–60%) and fibrosis (60–80%). The adolescent rats developed pneumonitis earlier following irradiation of the lung than did the adult rats leading to greater severe morbidity requiring euthanasia (~37% in adolescents vs. ~10% in young adults) but the extent of the mitigation of the damage was similar or slightly greater.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0401245</journal-id><journal-id journal-id-type="pubmed-jr-id">6844</journal-id><journal-id journal-id-type="nlm-ta">Radiat Res</journal-id><journal-id journal-id-type="iso-abbrev">Radiat. Res.</journal-id><journal-title-group><journal-title>Radiation research</journal-title></journal-title-group><issn pub-type="ppub">0033-7587</issn><issn pub-type="epub">1938-5404</issn></journal-meta><article-meta><article-id pub-id-type="pmid">23237541</article-id><article-id pub-id-type="pmc">3617812</article-id><article-id pub-id-type="doi">10.1667/RR2954.1</article-id><article-id pub-id-type="manuscript">NIHMS447613</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Mitigation of Radiation-Induced Lung Injury with EUK-207 and Genistein: Effects in Adolescent Rats</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Mahmood</surname><given-names>J.</given-names></name><xref ref-type="aff" rid="A1">a</xref><xref ref-type="aff" rid="A2">b</xref></contrib><contrib contrib-type="author"><name><surname>Jelveh</surname><given-names>S.</given-names></name><xref ref-type="aff" rid="A1">a</xref><xref ref-type="aff" rid="A2">b</xref></contrib><contrib contrib-type="author"><name><surname>Zaidi</surname><given-names>A.</given-names></name><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Doctrow</surname><given-names>S. R.</given-names></name><xref ref-type="aff" rid="A3">c</xref></contrib><contrib contrib-type="author"><name><surname>Hill</surname><given-names>R. P.</given-names></name><xref ref-type="aff" rid="A4">d</xref><xref rid="FN1" ref-type="author-notes">1</xref></contrib></contrib-group><aff id="A1"><label>a</label>Ontario Cancer Institute/Princess Margaret Cancer Center, University Health Network, and The Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada</aff><aff id="A2"><label>b</label>Radiation Medicine Program, STTARR Innovation Centre, Princess Margaret Hospital, Toronto, Ontario, Canada</aff><aff id="A3"><label>c</label>Pulmonary Center, Department of Medicine, Boston University, Boston, Massachusetts</aff><aff id="A4"><label>d</label>Departments of Medical Biophysics and Radiation Oncology, University of Toronto, Toronto, Ontario, Canada</aff><author-notes><corresp id="FN1"><label>1</label>Address for correspondence: Ontario Cancer Institute/Princess Margaret Cancer Center, 610 University Ave., Toronto, Ontario, Canada M5G 2M9; <email>hill@uhnres.utoronto.ca</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>19</day><month>3</month><year>2013</year></pub-date><pub-date pub-type="epub"><day>13</day><month>12</month><year>2012</year></pub-date><pub-date pub-type="ppub"><month>2</month><year>2013</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>2</month><year>2014</year></pub-date><volume>179</volume><issue>2</issue><fpage>125</fpage><lpage>134</lpage><permissions><copyright-statement>© 2013 by Radiation Research Society.</copyright-statement><copyright-year>2013</copyright-year></permissions><abstract><p id="P1">Exposure of civilian populations to radiation due to accident, war or terrorist act is an increasing concern. The lung is one of the more radiosensitive organs that may be affected in people receiving partial-body irradiation and radiation injury in lung is thought to be associated with the development of a prolonged inflammatory response. Here we examined how effectively damage to the lung can be mitigated by administration of drugs initiated at different times after radiation exposure and examined response in adolescent animals for comparison with the young adult animals that we had studied previously. We studied the mitigation efficacy of the isoflavone genistein (50 mg/kg) and the salen-Mn superoxide dismutase-catalase mimetic EUK-207 (8 mg/kg), both of which have been reported to scavenge reactive oxygen species and reduce activity of the NFkB pathway. The drugs were given by subcutaneous injection to 6- to 7-week-old Fisher rats daily starting either immediately or 2 weeks after irradiation with 12 Gy to the whole thorax. The treatment was stopped at 28 weeks post irradiation and the animals were assessed for levels of inflammatory cytokines, activated macrophages, oxidative damage and fibrosis at 48 weeks post irradiation. We demonstrated that both genistein and EUK-207 delayed and suppressed the increased breathing rate associated with pneumonitis. These agents also reduced levels of oxidative damage (50–100%), levels of TGF-β1 expression (75–100%), activated macrophages (20–60%) and fibrosis (60–80%). The adolescent rats developed pneumonitis earlier following irradiation of the lung than did the adult rats leading to greater severe morbidity requiring euthanasia (~37% in adolescents vs. ~10% in young adults) but the extent of the mitigation of the damage was similar or slightly greater.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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