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• W2793869069 abstract "Vitamin D3 and the synthetic vitamin D analogs, 1α-hydroxyvitamin D3 [1α(OH)D3 ], 1α-hydroxyvitamin D2 [1α(OH)D2 ] and 25-hydroxyvitamin D3 [25(OH)D3 ] were appraised for their vitamin D receptor (VDR) associated-potencies as cholesterol lowering agents in mice in vivo. These precursors are activated in vivo: 1α(OH)D3 and 1α(OH)D2 are transformed by liver CYP2R1 and CYP27A1 to active VDR ligands, 1α,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ] and 1α,25-dihydroxyvitamin D2 [1,25(OH)2 D2 ], respectively. 1α(OH)D2 may also be activated by CYP24A1 to 1α,24-dihydroxyvitamin D2 [1,24(OH)2 D2 ], another active VDR ligand. 25(OH)D3 , the metabolite formed via CYP2R1 and or CYP27A1 in liver from vitamin D3 , is activated by CYP27B1 in the kidney to 1,25(OH)2 D3 . In C57BL/6 mice fed the high fat/high cholesterol Western diet for 3 weeks, 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 (Shp) inhibition and increased cholesterol 7α-hydroxylase (Cyp7a1) expression, was: 1.75 nmol/kg 1α(OH)D3 > 1248 nmol/kg 25(OH)D3 (dose ratio of 0.0014) > > 1625 nmol/kg vitamin D3 . Except for 1.21 nmol/kg 1α(OH)D2 that failed to lower liver and plasma cholesterol contents, a significant negative correlation was observed between the liver concentration of 1,25(OH)2 D3 formed from the precursors and liver cholesterol levels. The composite results show that vitamin D analogs 1α(OH)D3 and 25(OH)D3 exhibit cholesterol lowering properties upon activation to 1,25(OH)2 D3 : 1α(OH)D3 is rapidly activated by liver enzymes and 25(OH)D3 is slowly activated by renal Cyp27b1 in mouse." @default.
• W2793869069 created "2018-03-29" @default.
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• W2793869069 date "2018-04-01" @default.
• W2793869069 modified "2023-10-17" @default.
• W2793869069 title "Potencies of vitamin D analogs, 1α‐hydroxyvitamin D₃, 1α‐hydroxyvitamin D₂ and 25‐hydroxyvitamin D₃, in lowering cholesterol in hypercholesterolemic mice <i>in vivo</i>" @default.
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• W2793869069 doi "https://doi.org/10.1002/bdd.2126" @default.
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