- Title
- Potential effects of phytoestrogen genistein in modulating acute methotrexate chemotherapy-induced osteoclastogenesis and bone damage in rats
- Creator
- King, Tristan J.; Shandala, Tetyana; Lee, Alice M.; Foster, Bruce K.; Chen, Ke-Ming; Howe, Peter R.; Xian, Cory J.
- Relation
- NHMRC
- Relation
- International Journal of Molecular Sciences Vol. 16, Issue 8, p. 18293-18311
- Publisher Link
- http://dx.doi.org/10.3390/ijms160818293
- Publisher
- MDPI AG
- Resource Type
- journal article
- Date
- 2015
- Description
- 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.
- Subject
- methotrexate; chemotherapy; osteoporosis; genistein
- Identifier
- http://hdl.handle.net/1959.13/1330868
- Identifier
- uon:26496
- Identifier
- ISSN:1661-6596
- 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/).
- Language
- eng
- Full Text
- Reviewed
- Hits: 4765
- Visitors: 4965
- Downloads: 243
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version (open access) | 2 MB | Adobe Acrobat PDF | View Details Download |