Abstract 1,25-Dihydroxyvitamin D 3 (1,25(OH) 2 D) has been shown to inhibit development of dextran sodium sulfate (DSS)-induced colitis in mice but can also cause hypercalcemia. The aim of this study was to evaluate whether β-glucuronides of vitamin D could deliver 1,25(OH) 2 D to the colon to ameliorate colitis while reducing the risk of hypercalcemia. Initial studies demonstrated that bacteria residing in the lower intestinal tract were capable of liberating 1,25(OH) 2 D from 1,25-dihydroxyvitamin D 3 -25-β-glucuronide (β-gluc-1,25(OH) 2 D). We also determined that a much greater upregulation of the vitamin D-dependent 24-hydroxylase gene (Cyp24) was induced in the colon by treatment of mice with an oral dose of β-gluc-1,25(OH) 2 D than 1,25(OH) 2 D, demonstrating targeted delivery of 1,25(OH) 2 D to the colon. We then tested β-glucuronides of vitamin D in the mouse DSS colitis model in two studies. In mice receiving DSS dissolved in distilled water and treated with 1,25(OH) 2 D or β-gluc-1,25(OH) 2 D, severity of colitis was reduced. Combination of β-gluc-1,25(OH) 2 D with 25-hydroxyvitamin D 3 -25-β-glucuronide (β-gluc-25(OH)D) resulted in the greatest reduction of colitis lesions and symptoms in DSS-treated mice. Plasma calcium concentrations were lower in mice treated with β-gluc-1,25(OH) 2 D alone or in combination with β-gluc-25(OH)D than in mice treated with 1,25(OH) 2 D, which were hypercalcemic at the time of death. β-Glucuronides of vitamin D compounds can deliver 1,25(OH) 2 D to the lower intestine and can reduce symptoms and lesions of acute colitis in this model. 1,25-dihydroxyvitamin D 3 1,25-dihydroxyvitamin D 3 -25-β-glucuronide 24-hydroxylase dextran sodium sulfate Copyright © 2012 the American Physiological Society « Previous | Next Article » Table of Contents This Article Published online before print November 2011 , doi: 10.​1152/​ajpgi.​00156.​2011 AJP - GI February 2012 vol. 302 no. 4 G460-G469 » Abstract Free Full Text Free to you Full Text (PDF) Free to you All Versions of this Article: ajpgi.00156.2011v1 302/4/G460 most recent Classifications Inflammation/Immunity/Mediators Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Goff, J. P. Articles by Horst, R. L. PubMed PubMed citation Articles by Goff, J. P. Articles by Horst, R. L. Related Content Load related web page information Current Issue February 2012, 302 (4) Alert me to new issues of AJP - GI About the Journal Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2012 the American Physiological Society Print ISSN: 0193-1857 Online ISSN: 1522-1547 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview();

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