{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:52:26Z","timestamp":1787593946971,"version":"build-2736575974"},"reference-count":39,"publisher":"The Company of Biologists","issue":"11","license":[{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"vor","delay-in-days":672,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"funder":[{"DOI":"10.13039\/501100000191","name":"Kidney Foundation of Canada","doi-asserted-by":"publisher","award":["KFOC160012"],"award-info":[{"award-number":["KFOC160012"]}],"id":[{"id":"10.13039\/501100000191","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008958","name":"Lawson Health Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008958","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008093","name":"Schulich School of Medicine and Dentistry","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008093","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Kidney stone disease involves the aggregation of stone-forming salts consequent to solute supersaturation in urine. The development of novel therapeutic agents for this predominantly metabolic and biochemical disorder have been hampered by the lack of a practical pre-clinical model amenable to drug screening. Here, Drosophila melanogaster, an emerging model for kidney stone disease research, was adapted as a high-throughput functional drug screening platform independent of the multifactorial nature of mammalian nephrolithiasis. Through functional screening, the therapeutic potential of a novel compound commonly known as arbutin that specifically binds to oxalate, a key component of kidney calculi, was identified. Through isothermal titration calorimetry, high-performance liquid chromatography and atomic force microscopy, arbutin was determined to interact with calcium and oxalate in both free and bound states, disrupting crystal lattice structure, growth and crystallization. When used to treat patient urine samples, arbutin significantly abrogated calculus formation in vivo and outperformed potassium citrate in low pH urine conditions, owing to its oxalate-centric mode of action. The discovery of this novel antilithogenic compound via D. melanogaster, independent of a mammalian model, brings greater recognition to this platform, for which metabolic features are primary outcomes, underscoring the power of D. melanogaster as a high-throughput drug screening platform in similar disorders. This is the first description of the use of D. melanogaster as the model system for a high-throughput chemical library screen.<\/jats:p>\n               <jats:p>This article has an associated First Person interview with the first authors of the paper.<\/jats:p>","DOI":"10.1242\/dmm.035873","type":"journal-article","created":{"date-parts":[[2018,8,6]],"date-time":"2018-08-06T07:45:43Z","timestamp":1533541543000},"source":"Crossref","is-referenced-by-count":21,"title":["<i>Drosophila melanogaster<\/i> as a function-based high-throughput screening model for antinephrolithiasis agents in kidney stone patients"],"prefix":"10.1242","volume":"11","author":[{"given":"Sohrab N.","family":"Ali","sequence":"first","affiliation":[{"name":"Schulich School of Medicine and Dentistry, Western University 1 Division of Urology, Department of Surgery , , London, ON N6A 4V2 , Canada"},{"name":"Lawson Health Research Institute 2 Translational Prostate Cancer Research Laboratory , , London, ON N6A 4V2 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thamara K.","family":"Dayarathna","sequence":"additional","affiliation":[{"name":"Schulich School of Medicine and Dentistry, Western University 1 Division of Urology, Department of Surgery , , London, ON N6A 4V2 , Canada"},{"name":"Lawson Health Research Institute 2 Translational Prostate Cancer Research Laboratory , , London, ON N6A 4V2 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aymon N.","family":"Ali","sequence":"additional","affiliation":[{"name":"Schulich School of Medicine and Dentistry, Western University 1 Division of Urology, Department of Surgery , , London, ON N6A 4V2 , Canada"},{"name":"Lawson Health Research Institute 2 Translational Prostate Cancer Research Laboratory , , London, ON N6A 4V2 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tijani","family":"Osumah","sequence":"additional","affiliation":[{"name":"Mayo Clinic 3 Department of Urology , , Rochester, MN 55905 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Mayo Clinic 3 Department of Urology , , Rochester, MN 55905 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler T.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Mayo Clinic 3 Department of Urology , , Rochester, MN 55905 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas E.","family":"Power","sequence":"additional","affiliation":[{"name":"Schulich School of Medicine and Dentistry, Western University 1 Division of Urology, Department of Surgery , , London, ON N6A 4V2 , Canada"},{"name":"Lawson Health Research Institute 2 Translational Prostate Cancer Research Laboratory , , London, ON N6A 4V2 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Western University 4 Department of Mechanical and Materials Engineering , , London, ON N6A 5B9 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dajung","family":"Kim","sequence":"additional","affiliation":[{"name":"Lawson Health Research Institute 2 Translational Prostate Cancer Research Laboratory , , London, ON N6A 4V2 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Kim","sequence":"additional","affiliation":[{"name":"Schulich School of Medicine and Dentistry, Western University 1 Division of Urology, Department of Surgery , , London, ON N6A 4V2 , Canada"},{"name":"Lawson Health Research Institute 2 Translational Prostate Cancer Research Laboratory , , London, ON N6A 4V2 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"St. Amant","sequence":"additional","affiliation":[{"name":"University of Santa Barbara 5 Department of Chemistry , , CA 93106 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqiang","family":"Hou","sequence":"additional","affiliation":[{"name":"Western University 6 Department of Chemistry , , London, ON N6A 3K7 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Tailly","sequence":"additional","affiliation":[{"name":"Schulich School of Medicine and Dentistry, Western University 1 Division of Urology, Department of Surgery , , London, ON N6A 4V2 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"Western University 4 Department of Mechanical and Materials Engineering , , London, ON N6A 5B9 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Len","family":"Luyt","sequence":"additional","affiliation":[{"name":"Western University 6 Department of Chemistry , , London, ON N6A 3K7 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Spagnuolo","sequence":"additional","affiliation":[{"name":"University of Guelph 7 Faculty of Food Sciences , , Guelph, ON N1G 2W1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy P.","family":"Burton","sequence":"additional","affiliation":[{"name":"Schulich School of Medicine and Dentistry, Western University 1 Division of Urology, Department of Surgery , , London, ON N6A 4V2 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Razvi","sequence":"additional","affiliation":[{"name":"Schulich School of Medicine and Dentistry, Western University 1 Division of Urology, Department of Surgery , , London, ON N6A 4V2 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7801-1402","authenticated-orcid":false,"given":"Hon 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Toxicol. Environ. Health"},{"key":"2024061302111250300_DMM035873C5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/gene.10150","article-title":"GAL4 system indrosophila: a fly geneticist's swiss army knife","volume":"34","author":"Duffy","year":"2002","journal-title":"Genesis"},{"key":"2024061302111250300_DMM035873C6","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.2215\/CJN.03210312","article-title":"Urolithiasis and the Risk of ESRD","volume":"7","author":"El-Zoghby","year":"2012","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"2024061302111250300_DMM035873C7","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.2215\/CJN.11661112","article-title":"Soda and other beverages and the risk of kidney stones","volume":"8","author":"Ferraro","year":"2013","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"2024061302111250300_DMM035873C8","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.3945\/ajcn.114.089987","article-title":"Caffeine intake and the risk of kidney stones","volume":"100","author":"Ferraro","year":"2014","journal-title":"Am. J. Clin. Nutr."},{"key":"2024061302111250300_DMM035873C9","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1503\/cmaj.051517","article-title":"Strategies for preventing calcium oxalate stones","volume":"174","author":"Finkielstein","year":"2006","journal-title":"Can. Med. Assoc. J."},{"key":"2024061302111250300_DMM035873C10","doi-asserted-by":"publisher","first-page":"19328","DOI":"10.1038\/srep19328","article-title":"Novel methods of determining urinary calculi composition: petrographic thin sectioning of calculi and nanoscale flow cytometry urinalysis","volume":"6","author":"Gavin","year":"2016","journal-title":"Sci. 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Physiol."},{"key":"2024061302111250300_DMM035873C13","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1016\/S0006-291X(02)00840-9","article-title":"Global analysis of differentially expressed genes during progression of calcium oxalate nephrolithiasis","volume":"296","author":"Katsuma","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2024061302111250300_DMM035873C14","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1007\/BF01367661","article-title":"Animal models of kidney stone formation: an analysis","volume":"15","author":"Khan","year":"1997","journal-title":"World J. Urol."},{"key":"2024061302111250300_DMM035873C15","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1016\/j.juro.2010.04.065","article-title":"Experimental induction of calcium oxalate nephrolithiasis in mice","volume":"184","author":"Khan","year":"2010","journal-title":"J. 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Nephrol."},{"key":"2024061302111250300_DMM035873C24","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/ki.2010.389","article-title":"Pharmacotherapy of urolithiasis: evidence from clinical trials","volume":"79","author":"Moe","year":"2011","journal-title":"Kidney Int."},{"key":"2024061302111250300_DMM035873C25","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1111\/j.1473-2165.2006.00253.x","article-title":"Hydroquinone and its analogues in dermatology - a risk-benefit viewpoint","volume":"5","author":"O'Donoghue","year":"2006","journal-title":"J. Cosmet. Dermatol."},{"key":"2024061302111250300_DMM035873C26","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1016\/S0140-6736(98)01295-1","article-title":"Kidney stones","volume":"351","author":"Pak","year":"1998","journal-title":"Lancet"},{"key":"2024061302111250300_DMM035873C27","first-page":"129","article-title":"Natural Resources Containing Arbutin. Determination of Arbutin in the Leaves of Bergenia crassifolia (L.) Fritsch. acclimated in Romania","volume":"37","author":"Pop","year":"2009","journal-title":"Not. Bot. Horti Agrobot. Cluj-Napoca"},{"key":"2024061302111250300_DMM035873C28","doi-asserted-by":"publisher","first-page":"659","DOI":"10.7326\/M13-2908","article-title":"Dietary and pharmacologic management to prevent recurrent nephrolithiasis in adults: a clinical practice guideline from the American College of Physicians","volume":"161","author":"Qaseem","year":"2014","journal-title":"Ann. Intern. Med."},{"key":"2024061302111250300_DMM035873C29","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1007\/BF00571844","article-title":"Effect of combined supplementation of magnesium oxide and pyridoxine in calcium-oxalate stone formers","volume":"22","author":"Rattan","year":"1994","journal-title":"Urol. 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