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Int. J. Mol. Sci. 2015, 16(8), 18293-18311; doi:10.3390/ijms160818293

Potential Effects of Phytoestrogen Genistein in Modulating Acute Methotrexate Chemotherapy-Induced Osteoclastogenesis and Bone Damage in Rats

1
Sansom Institute for Health Research, School of Pharmacy and Medical Science, University of South Australia, Adelaide, SA 5001, Australia
2
Department of Physiology, School of Medical Sciences, University of Adelaide, Adelaide, SA 5001, Australia
3
Department of Orthopaedic Surgery, Women's and Children's Hospital, North Adelaide, SA 5006, Australia
4
Institute of Orthopaedics, Lanzhou General Hospital, Lanzhou Command of Chinese People's Liberation Army, Lanzhou 730050, China
5
Nutritional Physiology Research Centre, School of Health Sciences, University of South Australia, Adelaide, SA 5001, Australia
6
Clinical Nutrition Research Centre, University of Newcastle, Callaghan, NSW 2308, Australia
*
Author to whom correspondence should be addressed.
Academic Editors: Paula Andrade and Patrícia Valentão
Received: 8 July 2015 / Accepted: 3 August 2015 / Published: 6 August 2015
(This article belongs to the Special Issue Phenolics and Polyphenolics 2015)
View Full-Text   |   Download PDF [3047 KB, uploaded 6 August 2015]   |  

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. View Full-Text
Keywords: methotrexate; chemotherapy; osteoporosis; genistein methotrexate; chemotherapy; osteoporosis; genistein
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MDPI and ACS Style

King, T.J.; Shandala, T.; Lee, A.M.; Foster, B.K.; Chen, K.-M.; Howe, P.R.; Xian, C.J. Potential Effects of Phytoestrogen Genistein in Modulating Acute Methotrexate Chemotherapy-Induced Osteoclastogenesis and Bone Damage in Rats. Int. J. Mol. Sci. 2015, 16, 18293-18311.

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