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

Article

King, Tristan J., Shandala, Tetyana, Lee, Alice M., Foster, Bruce K., Chen, Ke Ming, 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. https://doi.org/10.3390/ijms160818293
Article Title

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

ERA Journal ID41930
Article CategoryArticle
AuthorsKing, 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 TitleInternational Journal of Molecular Sciences
Journal Citation16 (8), pp. 18293-18311
Number of Pages19
Year2015
PublisherMDPI AG
Place of PublicationSwitzerland
ISSN1422-0067
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.

KeywordsChemotherapy; Genistein; Methotrexate; Osteoporosis; Drug Literature Index; Internal Medicine;
ANZSRC Field of Research 2020320216. Orthopaedics
Byline AffiliationsUniversity of South Australia
Department of Health, South Australia
Lanzhou General Hospital, China
Institution of OriginUniversity of Southern Queensland
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Fulton, Ashley S., Hill, Alison M., Williams, Marie T., Howe, Peter R. C. and Coates, Alison M.. 2015. "Paucity of evidence for a relationship between long-chain omega-3 fatty acid intake and chronic obstructive pulmonary disease: a systematic review." Nutrition Reviews. 73 (9), pp. 612-623. https://doi.org/10.1093/nutrit/nuv017
Combination chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil causes trabecular bone loss, bone marrow cell depletion and marrow adiposity in female rats
Fan, Chiaming, Georgiou, Kristen R., McKinnon, Ross A., Keefe, Dorothy M. K., Howe, Peter R. C. and Xian, Cory J.. 2016. "Combination chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil causes trabecular bone loss, bone marrow cell depletion and marrow adiposity in female rats." Journal of Bone and Mineral Metabolism. 34 (3), pp. 277-290. https://doi.org/10.1007/s00774-015-0679-x
Improvement of major depression is associated with increased erythrocyte DHA
Meyer, Barbara J., Grenyer, Brin F. S., Crowe, Trevor, Owen, Alice J., Grigonis-Deane, Elizabeth M. and Howe, Peter R. C.. 2013. "Improvement of major depression is associated with increased erythrocyte DHA." Lipids. 48 (9), pp. 863-868. https://doi.org/10.1007/s11745-013-3801-7
A randomised trial comparing low-fat diets differing in carbohydrate and protein ratio, combined with regular moderate intensity exercise, on glycaemic control, cardiometabolic risk factors, food cravings, cognitive function and psychological wellbeing in adults with type 2 diabetes: study protocol
Watson, Nerylee Ann, Dyer, Kathryn Ann, Buckley, Jonathan David, Brinkworth, Grant David, Coates, Alison Mary, Parfitt, Gaynor, Howe, Peter Ranald Charles, Noakes, Manny, Dye, Louise, Chadwick, Helen and Murphy, Karen Joy. 2015. "A randomised trial comparing low-fat diets differing in carbohydrate and protein ratio, combined with regular moderate intensity exercise, on glycaemic control, cardiometabolic risk factors, food cravings, cognitive function and psychological wellbeing in adults with type 2 diabetes: study protocol." Contemporary Clinical Trials. 45, pp. 217-225. https://doi.org/10.1016/j.cct.2015.11.001
Obesity: the new childhood disability?
Tsiros, M. D., Coates, A. M., Howe, P. R. C., Grimshaw, P. N. and Buckley, J. D.. 2011. "Obesity: the new childhood disability?" Obesity Reviews. 12 (1), pp. 26-36. https://doi.org/10.1111/j.1467-789X.2009.00706.x
Proximal correlates of metabolic phenotypes during 'at-risk' and 'case' stages of the metabolic disease continuum
Haren, M. T., Misan, G., Grant, J. F., Buckley, J. D., Howe, P. R. C., Taylor, A. W., Newbury, J. and McDermott, R. A.. 2012. "Proximal correlates of metabolic phenotypes during 'at-risk' and 'case' stages of the metabolic disease continuum." Nutrition and Diabetes. 2, pp. 1-11. https://doi.org/10.1038/nutd.2011.20
Erythrocyte polyunsaturated fatty acid status, memory, cognition and mood in older adults with mild cognitive impairment and healthy controls
Milte, Catherine M., Sinn, Natalie, Street, Steven J., Buckley, Jonathan D., Coates, Alison M. and Howe, Peter R. C.. 2011. "Erythrocyte polyunsaturated fatty acid status, memory, cognition and mood in older adults with mild cognitive impairment and healthy controls." Prostaglandins, Leukotrienes and Essential Fatty Acids. 84 (5-6), pp. 153-161. https://doi.org/10.1016/j.plefa.2011.02.002
Dairy consumption and cardiometabolic health: outcomes of a 12-month crossover trial
Crichton, Georgina E., Howe, Peter R. C., Buckley, Jonathan D., Coates, Alison M. and Murphy, Karen J.. 2012. "Dairy consumption and cardiometabolic health: outcomes of a 12-month crossover trial." Nutrition and Metabolism. 9 (19). https://doi.org/10.1186/1743-7075-9-19
Day-to-day physical functioning and disability in obese 10- to 13-year-olds
Tsiros, M. D., Buckley, J. D., Howe, P. R. C., Olds, T., Walkley, J., Taylor, L., Mallows, R., Hills, A. P., Kagawa, M. and Coates, A. M.. 2013. "Day-to-day physical functioning and disability in obese 10- to 13-year-olds." Pediatric Obesity. 8 (1), pp. 31-41. https://doi.org/10.1111/j.2047-6310.2012.00083.x
Fish oil in comparison to folinic acid for protection against adverse effects of methotrexate chemotherapy on bone
Raghu Nadhanan, Rethi, Fan, Chia Ming, Su, Yu Wen, Howe, Peter R. C. and Xian, Cory J.. 2014. "Fish oil in comparison to folinic acid for protection against adverse effects of methotrexate chemotherapy on bone." Journal of Orthopaedic Research. 32 (4), pp. 587-596. https://doi.org/10.1002/jor.22565
Interaction of erythrocyte eicosapentaenoic acid and physical activity predicts reduced risk of mild cognitive impairment
Street, Steven John, Parletta, Natalie, Milte, Catherine, Sullivan, Karen, Hills, Andrew P., Buckley, Jonathan and Howe, Peter. 2015. "Interaction of erythrocyte eicosapentaenoic acid and physical activity predicts reduced risk of mild cognitive impairment." Aging and Mental Health. 19 (10), pp. 885-891. https://doi.org/10.1080/13607863.2014.971705
Adiposity is related to decrements in cardiorespiratory fitness in obese and normal-weight children
Tsiros, M. D., Coates, A. M., Howe, P. R. C., Walkley, J., Hills, A. P., Wood, R. E. and Buckley, J. D.. 2016. "Adiposity is related to decrements in cardiorespiratory fitness in obese and normal-weight children." Pediatric Obesity. 11 (2), pp. 144-150. https://doi.org/10.1111/ijpo.12037
Telomere shortening in elderly individuals with mild cognitive impairment may be attenuated with ω-3 fatty acid supplementation: a randomized controlled pilot study
O'Callaghan, Nathan, Parletta, Natalie, Milte, Catherine M., Benassi-Evans, Bianca, Fenech, Michael and Howe, Peter R. C.. 2014. "Telomere shortening in elderly individuals with mild cognitive impairment may be attenuated with ω-3 fatty acid supplementation: a randomized controlled pilot study." Nutrition. 30 (4), pp. 489-491. https://doi.org/10.1016/j.nut.2013.09.013
Effects of low-fat diets differing in protein and carbohydrate content on cardiometabolic risk factors during weight loss and weight maintenance in obese adults with type 2 diabetes
Watson, Nerylee, Dyer, Kathryn, Buckley, Jonathan, Brinkworth, Grant, Coates, Alison, Parfitt, Gaynor, Howe, Peter, Noakes, Manny and Murphy, Karen. 2016. "Effects of low-fat diets differing in protein and carbohydrate content on cardiometabolic risk factors during weight loss and weight maintenance in obese adults with type 2 diabetes." Nutrients. 8 (5). https://doi.org/10.3390/nu8050289
Effects of resveratrol supplementation on bone growth in young rats and microarchitecture and remodeling in ageing rats
Lee, Alice M. C., Shandala, Tetyana, Nguyen, Long, Muhlhausler, Beverly S., Chen, Ke Ming, Howe, Peter R. and Xian, Cory J.. 2014. "Effects of resveratrol supplementation on bone growth in young rats and microarchitecture and remodeling in ageing rats." Nutrients. 6 (12), pp. 5871-5887. https://doi.org/10.3390/nu6125871
Eicosapentaenoic and docosahexaenoic acids, cognition, and behavior in children with attention-deficit/hyperactivity disorder: A randomized controlled trial
Milte, Catherine M., Parletta, Natalie, Buckley, Jonathan D., Coates, Alison M., Young, Ross M. and Howe, Peter R. C.. 2012. "Eicosapentaenoic and docosahexaenoic acids, cognition, and behavior in children with attention-deficit/hyperactivity disorder: A randomized controlled trial." Nutrition. 28 (6), pp. 670-677. https://doi.org/10.1016/j.nut.2011.12.009
Food groups and fatty acids associated with self-reported depression: An analysis from the Australian National Nutrition and Health Surveys
Meyer, Barbara J., Kolanu, Nithin, Griffiths, David A., Grounds, Ben, Howe, Peter R. C. and Kreis, Irene A.. 2013. "Food groups and fatty acids associated with self-reported depression: An analysis from the Australian National Nutrition and Health Surveys." Nutrition. 29 (7-8), pp. 1042-1047. https://doi.org/10.1016/j.nut.2013.02.006
Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure
Wong, R. H. X., Howe, P. R. C., Buckley, J. D., Coates, A. M., Kunz, I. and Berry, N. M.. 2011. "Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure." Nutrition Metabolism and Cardiovascular Diseases. 21 (11), pp. 851-856. https://doi.org/10.1016/j.numecd.2010.03.003
Chronic effects of a wild green oat extract supplementation on cognitive performance in older adults: a randomised, double-blind, placebo-controlled, crossover trial
Wong, Rachel H. X., Howe, Peter R. C., Bryan, Janet, Coates, Alison M., Buckley, Jonathan D. and Berry, Narelle M.. 2012. "Chronic effects of a wild green oat extract supplementation on cognitive performance in older adults: a randomised, double-blind, placebo-controlled, crossover trial." Nutrients. 4 (5), pp. 331-342. https://doi.org/10.3390/nu4050331
Effects of eating fresh lean pork on cardiometabolic health parameters
Murphy, Karen J., Thomson, Rebecca L., Coates, Alison M., Buckley, Jonathan D. and Howe, Peter R. C.. 2012. "Effects of eating fresh lean pork on cardiometabolic health parameters." Nutrients. 4 (7), pp. 711-723. https://doi.org/10.3390/nu4070711
Acknowledgment of reviewers
Howe, Peter. 2012. "Acknowledgment of reviewers." Nutrients. 4 (3), pp. 151-153. https://doi.org/10.3390/nu4030151
The Australian paradox
Howe, Peter. 2012. "The Australian paradox." Nutrients. 4 (4), p. 258. https://doi.org/10.3390/nu4040258
Dairy foods and dairy protein consumption is inversely related to markers of adiposity in obese men and women
Murphy, Karen J., Crichton, Georgina E., Dyer, Kathryn A., Coates, Alison M., Pettman, Tahna L., Milte, Catherine, Thorp, Alicia A., Berry, Narelle M., Buckley, Jonathan D., Noakes, Manny and Howe, Peter R. C.. 2013. "Dairy foods and dairy protein consumption is inversely related to markers of adiposity in obese men and women." Nutrients. 5 (11), pp. 4665-4684. https://doi.org/10.3390/nu5114665
Proceedings of the 2013 meeting of the Australasian Section of the American Oil Chemists Society (AAOCS)
Murphy, Karen and Howe, Peter. 2013. "Proceedings of the 2013 meeting of the Australasian Section of the American Oil Chemists Society (AAOCS)." Nutrients. 5 (12), pp. 5065-5096. https://doi.org/10.3390/nu5125065
A comparison of regular consumption of fresh lean pork, beef and chicken on body composition: A randomized cross-over trial
Murphy, Karen J., Parker, Barbara, Dyer, Kathryn A., Davis, Courtney R., Coates, Alison M., Buckley, Jonathan D. and Howe, Peter R. C.. 2014. "A comparison of regular consumption of fresh lean pork, beef and chicken on body composition: A randomized cross-over trial." Nutrients. 6 (2), pp. 682-696. https://doi.org/10.3390/nu6020682
Increases in plasma lutein through supplementation are correlated with increases in physical activity and reductions in sedentary time in older adults
Thomson, Rebecca L., Coates, Alison M., Howe, Peter R. C., Bryan, Janet, Matsumoto, Megumi and Buckley, Jonathan D.. 2014. "Increases in plasma lutein through supplementation are correlated with increases in physical activity and reductions in sedentary time in older adults." Nutrients. 6 (3), pp. 974-984. https://doi.org/10.3390/nu6030974
Relationship between erythrocyte omega-3 content and obesity is gender dependent
Howe, Peter R. C., Buckley, Jonathan D., Murphy, Karen J., Pettman, Tahna, Milte, Catherine and Coates, Alison M.. 2014. "Relationship between erythrocyte omega-3 content and obesity is gender dependent." Nutrients. 6 (5), pp. 1850-1860. https://doi.org/10.3390/nu6051850
Acute effects of a dietary non-starch polysaccharide supplement on cognitive performance in healthy middle-aged adults
Best, Talitha, Howe, Peter, Bryan, Janet, Buckley, Jonathan and Scholey, Andrew. 2015. "Acute effects of a dietary non-starch polysaccharide supplement on cognitive performance in healthy middle-aged adults." Nutritional Neuroscience. 18 (2), pp. 76-86. https://doi.org/10.1179/1476830513Y.0000000101
Effect of 12 weeks high oleic peanut consumption on cardio-metabolic risk factors and body composition
Barbour, Jayne A., Howe, Peter R. C., Buckley, Jonathan D., Bryan, Janet and Coates, Alison M.. 2015. "Effect of 12 weeks high oleic peanut consumption on cardio-metabolic risk factors and body composition." Nutrients. 7 (9), pp. 7381-7398. https://doi.org/10.3390/nu7095343
Improved heart rate recovery despite reduced exercise performance following heavy training: A within-subject analysis
Thomson, Rebecca L., Bellenger, Clint R., Howe, Peter R. C., Karavirta, Laura and Buckley, Jonathan D.. 2016. "Improved heart rate recovery despite reduced exercise performance following heavy training: A within-subject analysis." Journal of Science and Medicine in Sport. 19 (3), pp. 255-259. https://doi.org/10.1016/j.jsams.2015.02.010
Effect of acute exercise-induced fatigue on maximal rate of heart rate increase during submaximal cycling
Thomson, Rebecca L., Rogers, Daniel K., Howe, Peter R. C. and Buckley, Jonathan D.. 2016. "Effect of acute exercise-induced fatigue on maximal rate of heart rate increase during submaximal cycling." Research in Sports Medicine. 24 (1), pp. 1-15. https://doi.org/10.1080/15438627.2015.1076414
Monitoring athletic training status using the maximal rate of heart rate increase
Bellenger, Clint R., Thomson, Rebecca L., Howe, Peter R. C., Karavirta, Laura and Buckley, Jonathan D.. 2016. "Monitoring athletic training status using the maximal rate of heart rate increase." Journal of Science and Medicine in Sport. 19 (7), pp. 590-595. https://doi.org/10.1016/j.jsams.2015.07.006
Report on the Fifth International Conference on Natural Products for Health and Beauty (NATPRO 5) held in Thailand, 6–8th May, 2014
Voravuthikunchai, Supayang and Howe, Peter. 2014. "Report on the Fifth International Conference on Natural Products for Health and Beauty (NATPRO 5) held in Thailand, 6–8th May, 2014." Nutrients. 6 (10), pp. 4115-4164. https://doi.org/10.3390/nu6104115
Assessing premorbid cognitive ability in adults with Type 2 Diabetes Mellitus: a review with implications for future intervention studies
Wong, Rachel Heloise Xiwen, Scholey, Andrew and Howe, Peter Ranald Charles. 2014. "Assessing premorbid cognitive ability in adults with Type 2 Diabetes Mellitus: a review with implications for future intervention studies." Current Diabetes Reports. 14 (11). https://doi.org/10.1007/s11892-014-0547-4
Antihypertensive potential of combined extracts of olive leaf, green coffee bean and beetroot: a randomized, double-blind, placebo-controlled crossover trial
Wong, Rachel H. X., Garg, Manohar L., Wood, Lisa G. and Howe, Peter R. C.. 2014. "Antihypertensive potential of combined extracts of olive leaf, green coffee bean and beetroot: a randomized, double-blind, placebo-controlled crossover trial." Nutrients. 6 (11), pp. 4881-4894. https://doi.org/10.3390/nu6114881
Clinical evaluation of effects of chronic resveratrol supplementation on cerebrovascular function, cognition, mood, physical function and general well-being in postmenopausal women—rationale and study design
Evans, Hamish Michael, Howe, Peter Ranald Charles and Wong, Rachel Heloise Xiwen. 2016. "Clinical evaluation of effects of chronic resveratrol supplementation on cerebrovascular function, cognition, mood, physical function and general well-being in postmenopausal women—rationale and study design." Nutrients. 8 (3). https://doi.org/10.3390/nu8030150
Low dose resveratrol improves cerebrovascular function in type 2 diabetes mellitus
Wong, R. H. X., Nealon, R. S., Scholey, A. and Howe, P. R. C.. 2016. "Low dose resveratrol improves cerebrovascular function in type 2 diabetes mellitus." Nutrition Metabolism and Cardiovascular Diseases. 26 (5), pp. 393-399. https://doi.org/10.1016/j.numecd.2016.03.003
Acute resveratrol consumption improves neurovascular coupling capacity in adults with type 2 diabetes mellitus
Wong, Rachel H. X., Raederstorff, Daniel and Howe, Peter R. C.. 2016. "Acute resveratrol consumption improves neurovascular coupling capacity in adults with type 2 diabetes mellitus." Nutrients. 8 (7). https://doi.org/10.3390/nu8070425
Poor cerebrovascular function is an early marker of cognitive decline in healthy postmenopausal women
Wong, Rachel H. X., Evans, Hamish M. and Howe, Peter R. C.. 2016. "Poor cerebrovascular function is an early marker of cognitive decline in healthy postmenopausal women." Alzheimer's & Dementia: Translational Research & Clinical Interventions. 2 (3), pp. 162-168. https://doi.org/10.1016/j.trci.2016.07.003
Supplementation with fish oil and genistein, individually or in combination, protects bone against the adverse effects of methotrexate chemotherapy in rats
Nadhanan, Rethi Raghu, Skinner, Jayne, Chung, Rosa, Su, Yu-Wen, Howe, Peter R. and Xian, Cory J.. 2013. "Supplementation with fish oil and genistein, individually or in combination, protects bone against the adverse effects of methotrexate chemotherapy in rats." PLoS One. 8 (8). https://doi.org/10.1371/journal.pone.0071592