{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T21:53:56Z","timestamp":1768686836695,"version":"3.49.0"},"reference-count":56,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,4,25]],"date-time":"2018-04-25T00:00:00Z","timestamp":1524614400000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003579","name":"University of Toronto","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003579","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Vitamin D<jats:sub>3<\/jats:sub> and the synthetic vitamin D analogs, 1\u03b1\u2010hydroxyvitamin D<jats:sub>3<\/jats:sub> [1\u03b1(OH)D<jats:sub>3<\/jats:sub>], 1\u03b1\u2010hydroxyvitamin D<jats:sub>2<\/jats:sub> [1\u03b1(OH)D<jats:sub>2<\/jats:sub>] and 25\u2010hydroxyvitamin D<jats:sub>3<\/jats:sub> [25(OH)D<jats:sub>3<\/jats:sub>] were appraised for their vitamin D receptor (VDR) associated\u2010potencies as cholesterol lowering agents in mice <jats:italic>in vivo<\/jats:italic>. These precursors are activated <jats:italic>in vivo<\/jats:italic>: 1\u03b1(OH)D<jats:sub>3<\/jats:sub> and 1\u03b1(OH)D<jats:sub>2<\/jats:sub> are transformed by liver CYP2R1 and CYP27A1 to active VDR ligands, 1\u03b1,25\u2010dihydroxyvitamin D<jats:sub>3<\/jats:sub> [1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>] and 1\u03b1,25\u2010dihydroxyvitamin D<jats:sub>2<\/jats:sub> [1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>2<\/jats:sub>]<jats:sub>,<\/jats:sub> respectively. 1\u03b1(OH)D<jats:sub>2<\/jats:sub> may also be activated by CYP24A1 to 1\u03b1,24\u2010dihydroxyvitamin D<jats:sub>2<\/jats:sub> [1,24(OH)<jats:sub>2<\/jats:sub>D<jats:sub>2<\/jats:sub>], another active VDR ligand. 25(OH)D<jats:sub>3<\/jats:sub>, the metabolite formed via CYP2R1 and or CYP27A1 in liver from vitamin D<jats:sub>3<\/jats:sub>, is activated by CYP27B1 in the kidney to 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>. In C57BL\/6 mice fed the high fat\/high cholesterol Western diet for 3\u00a0weeks, vitamin D analogs were administered every other day intraperitoneally during the last week of the diet. The rank order for cholesterol lowering, achieved via mouse liver small heterodimer partner (<jats:italic>Shp<\/jats:italic>) inhibition and increased cholesterol 7\u03b1\u2010hydroxylase (<jats:italic>Cyp7a1<\/jats:italic>) expression, was: 1.75\u00a0nmol\/kg 1\u03b1(OH)D<jats:sub>3<\/jats:sub>\u00a0&gt;\u00a01248\u00a0nmol\/kg 25(OH)D<jats:sub>3<\/jats:sub> (dose ratio of 0.0014) &gt;\u00a0&gt;\u00a01625\u00a0nmol\/kg vitamin D<jats:sub>3<\/jats:sub>. Except for 1.21\u00a0nmol\/kg 1\u03b1(OH)D<jats:sub>2<\/jats:sub> that failed to lower liver and plasma cholesterol contents, a significant negative correlation was observed between the liver concentration of 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> formed from the precursors and liver cholesterol levels. The composite results show that vitamin D analogs 1\u03b1(OH)D<jats:sub>3<\/jats:sub> and 25(OH)D<jats:sub>3<\/jats:sub> exhibit cholesterol lowering properties upon activation to 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>: 1\u03b1(OH)D<jats:sub>3<\/jats:sub> is rapidly activated by liver enzymes and 25(OH)D<jats:sub>3<\/jats:sub> is slowly activated by renal Cyp27b1 in mouse.<\/jats:p>","DOI":"10.1002\/bdd.2126","type":"journal-article","created":{"date-parts":[[2018,2,28]],"date-time":"2018-02-28T03:26:40Z","timestamp":1519788400000},"page":"196-204","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Potencies of vitamin D analogs, 1\u03b1\u2010hydroxyvitamin D<sub>3<\/sub>, 1\u03b1\u2010hydroxyvitamin D<sub>2<\/sub> and 25\u2010hydroxyvitamin D<sub>3<\/sub>, in lowering cholesterol in hypercholesterolemic mice <i>in vivo<\/i>"],"prefix":"10.1002","volume":"39","author":[{"given":"Holly P.","family":"Quach","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"Dzekic","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Bukuroshi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0683-2129","authenticated-orcid":false,"given":"K. 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