Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/94233
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dc.contributor.author | King, T. | - |
dc.contributor.author | Shandala, T. | - |
dc.contributor.author | Lee, A. | - |
dc.contributor.author | Foster, B. | - |
dc.contributor.author | Chen, K. | - |
dc.contributor.author | Howe, P. | - |
dc.contributor.author | Xian, C. | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | International Journal of Molecular Sciences, 2015; 16(8):18293-18311 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.issn | 1422-0067 | - |
dc.identifier.uri | http://hdl.handle.net/2440/94233 | - |
dc.description.abstract | Chemotherapy-induced bone damage is a frequent side effect which causes diminished bone mineral density and fracture in childhood cancer sufferers and survivors. The intensified use of anti-metabolite methotrexate (MTX) and other cytotoxic drugs has led to the need for a mechanistic understanding of chemotherapy-induced bone loss and for the development of protective treatments. Using a young rat MTX-induced bone loss model, we investigated potential bone protective effects of phytoestrogen genistein. Oral gavages of genistein (20 mg/kg) were administered daily, for seven days before, five days during, and three days after five once-daily injections (sc) of MTX (0.75 mg/kg). MTX treatment reduced body weight gain and tibial metaphyseal trabecular bone volume (p < 0.001), increased osteoclast density on the trabecular bone surface (p < 0.05), and increased the bone marrow adipocyte number in lower metaphyseal bone (p < 0.001). Genistein supplementation preserved body weight gain (p < 0.05) and inhibited ex vivo osteoclast formation of bone marrow cells from MTX-treated rats (p < 0.001). However, MTX-induced changes in bone volume, trabecular architecture, metaphyseal mRNA expression of pro-osteoclastogenic cytokines, and marrow adiposity were not significantly affected by the co-administration of genistein. This study suggests that genistein may suppress MTX-induced osteoclastogenesis; however, further studies are required to examine its potential in protecting against MTX chemotherapy-induced bone damage. | - |
dc.description.statementofresponsibility | Tristan J. King, Tetyana Shandala, Alice M. Lee, Bruce K. Foster, Ke-Ming Chen, Peter R. Howe, and Cory J. Xian | - |
dc.language.iso | en | - |
dc.publisher | MDPI AG | - |
dc.rights | © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). | - |
dc.source.uri | http://dx.doi.org/10.3390/ijms160818293 | - |
dc.subject | Methotrexate; chemotherapy; osteoporosis; genistein | - |
dc.title | Potential effects of phytoestrogen genistein in modulating acute methotrexate chemotherapy-induced osteoclastogenesis and bone damage in rats | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.3390/ijms160818293 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Howe, P. [0000-0001-6546-7742] | - |
dc.identifier.orcid | Xian, C. [0000-0002-8467-2845] | - |
Appears in Collections: | Aurora harvest 2 Medicine publications |
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hdl_94233.pdf | Published version | 2.64 MB | Adobe PDF | View/Open |
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