Mitigation of radiation-induced lung injury by Genistein and EUK-207
Identifieur interne : 001637 ( Main/Exploration ); précédent : 001636; suivant : 001638Mitigation of radiation-induced lung injury by Genistein and EUK-207
Auteurs : J. Mahmood [Canada, Malaisie] ; S. Jelveh [Canada] ; V. Calveley [Canada] ; A. Zaidi [Canada] ; Sr Doctrow [États-Unis] ; Rp Hill [Canada]Source :
- International journal of radiation biology [ 0955-3002 ] ; 2011.
Abstract
We examined the effects of genistein and/or Eukarion (EUK)-207 on radiation-induced lung damage and investigated whether treatment for 0–14 weeks (wks) post-irradiation (PI) would mitigate late lung injury.
The lungs of female Sprague-Dawley (SD) rats were irradiated with 10 Gy. EUK-207 was delivered by infusion and genistein was delivered as a dietary supplement starting immediately after irradiation (PI) and continuing until 14 wks PI. Rats were sacrificed at 0, 4, 8, 14 and 28 wks PI. Breathing rate was monitored and lung fibrosis assessed by lung hydroxyproline content at 28 wks. DNA damage was assessed by micronucleus (MN) assay and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. The expression of the cytokines Interleukin (IL)-1α, IL-1β, IL-6, Tumor necrotic factor (TNF)-α and Transforming growth factor (TGF)-β1, and macrophage activation were analysed by immunohistochemistry.
Increases in breathing rate observed in the irradiated rats were significantly reduced by both drug treatments during the pneumonitis phase and the later fibrosis phase. The drug treatments decreased micronuclei (MN) formation from 4–14 wks but by 28 wks the MN levels had increased again. The 8-OHdG levels were lower in the drug treated animals at all time points. Hydroxyproline content and levels of activated macrophages were decreased at 28 wks in all drug treated rats. The treatments had limited effects on the expression of the cytokines.
Genistein, and EUK-207 can provide partial mitigation of radiation-induced lung damage out to at least 28 wks PI even after cessation of treatment at 14 wks PI.
Url:
DOI: 10.3109/09553002.2011.583315
PubMed: 21675818
PubMed Central: 3155801
Affiliations:
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Mahmood</name><affiliation wicri:level="1"><nlm:aff id="A1">Ontario Cancer Institute/ Princess Margaret Hospital, University Health Network, and the Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Canada</country><wicri:regionArea>Ontario Cancer Institute/ Princess Margaret Hospital, University Health Network, and the Campbell Family Institute for Cancer Research, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Faculty of Dentistry, Universiti Teknologi MARA (UiTM), Shah Alam, Malaysia.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Malaisie</country><wicri:regionArea>Faculty of Dentistry, Universiti Teknologi MARA (UiTM), Shah Alam</wicri:regionArea><wicri:noRegion>Shah Alam</wicri:noRegion></affiliation></author><author><name sortKey="Jelveh, S" sort="Jelveh, S" uniqKey="Jelveh S" first="S" last="Jelveh">S. 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Mahmood</name><affiliation wicri:level="1"><nlm:aff id="A1">Ontario Cancer Institute/ Princess Margaret Hospital, University Health Network, and the Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Canada</country><wicri:regionArea>Ontario Cancer Institute/ Princess Margaret Hospital, University Health Network, and the Campbell Family Institute for Cancer Research, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Faculty of Dentistry, Universiti Teknologi MARA (UiTM), Shah Alam, Malaysia.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Malaisie</country><wicri:regionArea>Faculty of Dentistry, Universiti Teknologi MARA (UiTM), Shah Alam</wicri:regionArea><wicri:noRegion>Shah Alam</wicri:noRegion></affiliation></author><author><name sortKey="Jelveh, S" sort="Jelveh, S" uniqKey="Jelveh S" first="S" last="Jelveh">S. Jelveh</name><affiliation wicri:level="1"><nlm:aff id="A1">Ontario Cancer Institute/ Princess Margaret Hospital, University Health Network, and the Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Canada</country><wicri:regionArea>Ontario Cancer Institute/ Princess Margaret Hospital, University Health Network, and the Campbell Family Institute for Cancer Research, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Calveley, V" sort="Calveley, V" uniqKey="Calveley V" first="V" last="Calveley">V. 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EUK-207 was delivered by infusion and genistein was delivered as a dietary supplement starting immediately after irradiation (PI) and continuing until 14 wks PI. Rats were sacrificed at 0, 4, 8, 14 and 28 wks PI. Breathing rate was monitored and lung fibrosis assessed by lung hydroxyproline content at 28 wks. DNA damage was assessed by micronucleus (MN) assay and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. The expression of the cytokines Interleukin (IL)-1α, IL-1β, IL-6, Tumor necrotic factor (TNF)-α and Transforming growth factor (TGF)-β1, and macrophage activation were analysed by immunohistochemistry.</p></sec><sec id="S3"><title>Results</title><p id="P3">Increases in breathing rate observed in the irradiated rats were significantly reduced by both drug treatments during the pneumonitis phase and the later fibrosis phase. The drug treatments decreased micronuclei (MN) formation from 4–14 wks but by 28 wks the MN levels had increased again. The 8-OHdG levels were lower in the drug treated animals at all time points. Hydroxyproline content and levels of activated macrophages were decreased at 28 wks in all drug treated rats. The treatments had limited effects on the expression of the cytokines.</p></sec><sec id="S4"><title>Conclusion</title><p id="P4">Genistein, and EUK-207 can provide partial mitigation of radiation-induced lung damage out to at least 28 wks PI even after cessation of treatment at 14 wks PI.</p></sec></div></front></TEI><affiliations><list><country><li>Canada</li><li>Malaisie</li><li>États-Unis</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><noRegion><name sortKey="Mahmood, J" sort="Mahmood, J" uniqKey="Mahmood J" first="J" last="Mahmood">J. Mahmood</name></noRegion><name sortKey="Calveley, V" sort="Calveley, V" uniqKey="Calveley V" first="V" last="Calveley">V. Calveley</name><name sortKey="Hill, Rp" sort="Hill, Rp" uniqKey="Hill R" first="Rp" last="Hill">Rp Hill</name><name sortKey="Hill, Rp" sort="Hill, Rp" uniqKey="Hill R" first="Rp" last="Hill">Rp Hill</name><name sortKey="Jelveh, S" sort="Jelveh, S" uniqKey="Jelveh S" first="S" last="Jelveh">S. Jelveh</name><name sortKey="Zaidi, A" sort="Zaidi, A" uniqKey="Zaidi A" first="A" last="Zaidi">A. Zaidi</name></country><country name="Malaisie"><noRegion><name sortKey="Mahmood, J" sort="Mahmood, J" uniqKey="Mahmood J" first="J" last="Mahmood">J. Mahmood</name></noRegion></country><country name="États-Unis"><noRegion><name sortKey="Doctrow, Sr" sort="Doctrow, Sr" uniqKey="Doctrow S" first="Sr" last="Doctrow">Sr Doctrow</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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