Potential effects of phytoestrogen genistein in modulating acute methotrexate chemotherapy-induced osteoclastogenesis and bone damage in rats

King, Tristan J. and Shandala, Tetyana and Lee, Alice M. and Foster, Bruce K. and Chen, Ke Ming and Howe, Peter R. and Xian, Cory J. (2015) Potential effects of phytoestrogen genistein in modulating acute methotrexate chemotherapy-induced osteoclastogenesis and bone damage in rats. International Journal of Molecular Sciences, 16 (8). pp. 18293-18311. ISSN 1661-6596

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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.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Published version made available under Open Access.
Faculty / Department / School: No Faculty
Date Deposited: 05 Jun 2017 02:46
Last Modified: 27 Jun 2017 02:39
Uncontrolled Keywords: Chemotherapy; Genistein; Methotrexate; Osteoporosis; Drug Literature Index; Internal Medicine;
Fields of Research : 11 Medical and Health Sciences > 1103 Clinical Sciences > 110314 Orthopaedics
Socio-Economic Objective: E Expanding Knowledge > 97 Expanding Knowledge > 970111 Expanding Knowledge in the Medical and Health Sciences
Identification Number or DOI: 10.3390/ijms160818293
URI: http://eprints.usq.edu.au/id/eprint/31611

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