Potential effects of phytoestrogen genistein in modulating acute methotrexate chemotherapy-induced osteoclastogenesis and bone damage in rats
Article
Article Title | Potential effects of phytoestrogen genistein in modulating acute methotrexate chemotherapy-induced osteoclastogenesis and bone damage in rats |
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ERA Journal ID | 41930 |
Article Category | Article |
Authors | King, Tristan J. (Author), Shandala, Tetyana (Author), Lee, Alice M. (Author), Foster, Bruce K. (Author), Chen, Ke Ming (Author), Howe, Peter R. (Author) and Xian, Cory J. (Author) |
Journal Title | International Journal of Molecular Sciences |
Journal Citation | 16 (8), pp. 18293-18311 |
Number of Pages | 19 |
Year | 2015 |
Publisher | MDPI AG |
Place of Publication | Switzerland |
ISSN | 1422-0067 |
Digital Object Identifier (DOI) | https://doi.org/10.3390/ijms160818293 |
Web Address (URL) | http://www.mdpi.com/1422-0067/16/8/18293/htm |
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. |
Keywords | Chemotherapy; Genistein; Methotrexate; Osteoporosis; Drug Literature Index; Internal Medicine; |
ANZSRC Field of Research 2020 | 320216. Orthopaedics |
Byline Affiliations | University of South Australia |
Department of Health, South Australia | |
Lanzhou General Hospital, China | |
Institution of Origin | University of Southern Queensland |
https://research.usq.edu.au/item/q4113/potential-effects-of-phytoestrogen-genistein-in-modulating-acute-methotrexate-chemotherapy-induced-osteoclastogenesis-and-bone-damage-in-rats
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