Effect of Phenobarbitone Treatment on Vitamin D Metabolism in Mammals

1974 ◽  
Vol 46 (4) ◽  
pp. 433-448 ◽  
Author(s):  
J. Silver ◽  
G. Neale ◽  
G. R. Thompson
Keyword(s):  
Vitamin D ◽  
Biological Activity ◽  
Silicic Acid ◽  
Vitamin D3 ◽  
Water Soluble ◽  
Prolonged Treatment ◽  
Vitamin D Metabolism ◽  
Silicic Acid Chromatography ◽  
Polar Metabolites ◽  
25 Hydroxycholecalciferol

1. The metabolism of radioactive cholecalciferol was studied in control and phenobarbitone-treated rats and pigs. 2. Treatment with phenobarbitone enhanced the appearance in plasma of 25-hydroxycholecalciferol (peak IV on silicic acid chromatography), and of more-polar metabolites (peak V), but not of the most-polar metabolites (peak VI). Peak IV had the chromatographic properties of authentic 25-hydroxycholecalciferol (25-HCC) and had biological activity. 3. There was no effect on the appearance of peaks V and VI in plasma after an injection of radioactive 25-HCC. 4. Treatment with phenobarbitone enhanced the excretion of metabolites of radioactive vitamin D3 in bile. These metabolites were largely water-soluble conjugates of peaks IV, V and VI, which included glucuronides. Peak IV in bile was not identical with 25-HCC. 5. Prolonged treatment with phenobarbitone depleted the tissue radioactivity of rats given radioactive vitamin D3.

scholarly journals Investigations on metabolites of vitamin D in rat bile. Separation and partial identification of a major metabolite

1969 ◽  
Vol 115 (4) ◽  
pp. 663-669 ◽  
Author(s):  
P. A. Bell ◽  
E. Kodicek
Keyword(s):  
Vitamin D ◽  
Silicic Acid ◽  
Intravenous Infusion ◽  
Similar Pattern ◽  
Bile Ducts ◽  
Gradient Elution ◽  
Partial Identification ◽  
Polar Metabolites ◽  
Rat Bile ◽  
25 Hydroxycholecalciferol

1. Young rats with cannulated bile ducts were given 0·34mg. of [1α−3H]cholecalciferol or 0·54mg. of [14C]ergocalciferol by intravenous infusion. Of the radioactivity in the dose of [1α−3H]cholecalciferol 31% was recovered in bile within 24hr. 2. The metabolites in bile were separated by gradient-elution column chromatography on silicic acid into five components, all more polar than cholecalciferol or 25-hydroxycholecalciferol. [14C]Ergocalciferol gave a similar pattern of metabolites in bile. 3. The three most polar metabolites were shown to be ionic. The major component has been identified as a glucuronide conjugate, which was not identical with synthetic cholecalciferyl glucuronide.

scholarly journals The effect of disodium ethane-1-hydroxy-1,1-diphosphonate on the metabolism of calcitriol in chicks

1987 ◽  
Vol 243 (1) ◽  
pp. 75-78 ◽  
Author(s):  
C Lidor ◽  
M S Meyer ◽  
R H Wasserman ◽  
S Edelstein
Keyword(s):  
Vitamin D ◽  
Urinary Excretion ◽  
Intestinal Absorption ◽  
Binding Protein ◽  
Sole Source ◽  
Treated Group ◽  
Response To Treatment ◽  
Vitamin D Metabolism ◽  
Calbindin D28k ◽  
25 Hydroxycholecalciferol

Decreased intestinal absorption of Ca2+ occurs in response to treatment with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP). The effect is due to decreased 1-hydroxylation of calcidiol (25-hydroxycholecalciferol) in the kidney. In an attempt to establish whether impairment of vitamin D metabolism at steps beyond kidney hydroxylation occurs due to treatment with EHDP, chicks were depleted of vitamin D and were treated with calcitriol (1,25-dihydroxycholecalciferol) as their sole source of the vitamin. The chicks were then divided into two groups, one being treated with EHDP while the second group served as control. Intestinal absorption of Ca2+ in the EHDP-treated group was found to be impaired, along with decreases in concentrations of calbindin D28K (the 28,000-Mr vitamin D-dependent Ca2+-binding protein). When the chicks were dosed with [3H]calcitriol, significantly lower concentrations of the sterol were detected in the duodena of EHDP-treated birds. Measurement of levels of receptors for calcitriol in duodena showed no difference between groups, but levels of calcitriol in sera were considerably lower in the EHDP-treated group along with the elevated biliary and urinary excretion of glucuronidated conjugates. It is therefore concluded that treatment with EHDP results in increased catabolism of calcitriol in addition to the known suppression of the renal production of the hormone.

scholarly journals Lack of biological activity of vitamin D3-3β sulfate during lactation in vitamin D-deficient rats

1987 ◽  
Vol 27 (6) ◽  
pp. 979-997 ◽  
Author(s):  
Leonor CANCELA ◽  
P. J. MARIE ◽  
Noélie LE BOULCH ◽  
Livia MIRAVET
Keyword(s):  
Vitamin D ◽  
Biological Activity ◽  
Vitamin D3

Intestinal metabolism and portal venous transport of 1,25(OH)2D3, 25(OH)D3, and vitamin D3 in the rat

1985 ◽  
Vol 248 (6) ◽  
pp. G633-G638 ◽  
Author(s):  
G. B. McDonald ◽  
K. H. Lau ◽  
A. L. Schy ◽  
J. E. Wergedal ◽  
D. J. Baylink
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
High Performance ◽  
Average Rate ◽  
Venous Blood ◽  
Intestinal Metabolism ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Polar Metabolites

We compared the intestinal absorption of three vitamin D3 sterols and tested the hypothesis that the intestine hydroxylates absorbed vitamin D and transports polar metabolites in portal venous blood. Micellar solutions containing 50 nmol of a radiolabeled vitamin D3 sterol (1,25-dihydroxyvitamin D3, 25-hydroxyvitamin D3, or vitamin D3) were placed in closed jejunal segments of rats prepared with lymphatic and mesenteric venous fistulas. Venous blood loss was replaced by infusion of donor rat blood into the saphenous vein. After 1-2 h the rats were killed, and intestinal homogenates, mesenteric blood, and lymph were analyzed. The average rate of absorption of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] was two- and fivefold higher than that of 25-hydroxyvitamin D3 [25(OH)D3] and vitamin D3 (D3), respectively. Transport of hydroxylated vitamin D sterols was primarily via the venous route; the average rate of venous transport of 1,25(OH)2D3 was 18.3 X 10(2) nmol X min-1 X g-1 compared with 8.8 X 10(2) for 25(OH)D3 and 0.13 X 10(2) for D3. High-performance liquid chromatography of intestinal and plasma extracts revealed that there was 25-hydroxylation of absorbed D3, 24- and putative 1-hydroxylation of absorbed 25(OH)D3, and prompt portal venous transport of all hydroxylated metabolites. When 1,25(OH)2D3 was infused into the lumen, the composition of radiolabeled sterols found in intestinal homogenates and mesenteric venous plasma was virtually identical to that of the infusate. These studies provide in vivo evidence for the intestinal metabolism of pharmacological quantities of absorbed vitamin D3 sterols and the prompt portal venous transport of more polar metabolites.

scholarly journals Effect of oestrogen and 1,25-dihydroxycholecalciferol on 25-hydroxycholecalciferol metabolism in primary chick kidney-cell cultures

1978 ◽  
Vol 174 (1) ◽  
pp. 231-236 ◽  
Author(s):  
E Spanos ◽  
D I Barrett ◽  
K T Chong ◽  
I MacIntyre
Keyword(s):  
Vitamin D ◽  
Cell Cultures ◽  
Kidney Cell ◽  
Primary Cultures ◽  
Kidney Cells ◽  
Hydroxylase Activity ◽  
Experimental Conditions ◽  
Polar Metabolites ◽  
Chick Kidney ◽  
25 Hydroxycholecalciferol

Primary cultures of chick kidney cells convert 25-hydroxycholecalciferol into more-polar metabolites. Cells from vitamin D-deficient chicks have high 25-hydroxycholecalciferol 1 alpha-hydroxylase (1 alpha-hydroxylase) activity, but no 25-hydroxycholecalciferol 24-hydroxylase (24-hydroxylase) activity. Physiological concentrations of 1,25-dihydroxycholeclaciferol suppress 1 alpha-hydroxylase and induce 24-hydroxylase activity. The inhibition of 1 alpha-hydroxylase preceded the induction of 24-hydroxylase. In contrast, oestradiol-17 beta had no effect on the activity of either hydroxylase under a variety of experimental conditions. These results clearly demonstrate that 1,25-dihydroxycholecalciferol, but not oestrogen, acts directly on the kidney cells to regulate the metabolism of 25-hydroxycholecalciferol.

scholarly journals Differential Effects of Oral Boluses of Vitamin D2 vs Vitamin D3 on Vitamin D Metabolism: A Randomized Controlled Trial

2019 ◽  
Vol 104 (12) ◽  
pp. 5831-5839 ◽  
Author(s):  
Adrian R Martineau ◽  
Kenneth E Thummel ◽  
Zhican Wang ◽  
David A Jolliffe ◽  
Barbara J Boucher ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Bolus Dose ◽  
Total Serum ◽  
Vitamin D2 ◽  
Serum Concentrations ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D3 ◽  
Differential Effects ◽  
The Mean

Abstract Context Vitamin D2 and vitamin D3 have been hypothesized to exert differential effects on vitamin D metabolism. Objective To compare the influence of administering vitamin D2 vs vitamin D3 on metabolism of vitamin D3. Methods We measured baseline and 4-month serum concentrations of vitamin D3, 25-hydroxyvitamin D3 [25(OH)D3], 25-hydroxyvitamin D2, 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3], 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], and 4β,25-dihydroxyvitamin D3 [4β,25(OH)2D3] in 52 adults randomized to receive a total of four oral bolus doses of 2.5 mg vitamin D2 (n = 28) or vitamin D3 (n = 24) over four months. Metabolite-to-parent compound ratios were calculated to estimate hydroxylase activity. Pairwise before vs after comparisons were made to evaluate effects of vitamin D2 and vitamin D3 on metabolism of vitamin D. Mean postsupplementation metabolite-to-parent ratios were then compared between groups. Results Vitamin D2 was less effective than vitamin D3 in elevating total serum 25(OH)D concentration. Vitamin D2 suppressed mean four-month serum concentrations of 25(OH)D3, 24R,25(OH)2D3, 1α,25(OH)2D3, and 4β,25(OH)2D3 and mean ratios of 25(OH)D3 to D3 and 1α,25(OH)2D3 to 25(OH)D3, while increasing the mean ratio of 24R,25(OH)2D3 to 25(OH)D3. Vitamin D3 increased mean four-month serum concentrations of 25(OH)D3, 24R,25(OH)2D3, 1α,25(OH)2D3, and 4β,25(OH)2D3 and the mean ratio of 24R,25(OH)2D3 to 25(OH)D3. Participants receiving vitamin D2 had lower mean postsupplementation ratios of 25(OH)D3 to vitamin D3 and 1α,25(OH)2D3 to 25(OH)D3 than those receiving vitamin D3. Mean postsupplementation ratios of 24R,25(OH)2D3 to 25(OH)D3 and 4β,25(OH)2D3 to 25(OH)D3 did not differ between groups. Conclusions Bolus-dose vitamin D2 is less effective than bolus-dose vitamin D3 in elevating total serum 25(OH)D concentration. Administration of vitamin D2 reduces 25-hydroxylation of vitamin D3 and 1-α hydroxylation of 25(OH)D3, while increasing 24R-hydroxylation of 25(OH)D3.

Biological activity of 26,26,26,27,27,27-hexafluoro- 1,25-dihydroxyvitamin D3 in the chick

1989 ◽  
Vol 121 (4) ◽  
pp. 520-524 ◽  
Author(s):  
Takeshi Kiriyama ◽  
Sumiaki Okamoto ◽  
Hiroyuki Suzuki ◽  
Akihiko Nagata ◽  
Motomori Izumi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Biological Activity ◽  
Inorganic Phosphorus ◽  
Binding Ability ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D3 ◽  
X Ray ◽  
Dihydroxyvitamin D ◽  
Increased Activity ◽  
Biological Differences

Abstract. A newly synthesized fluorinated analogue of 1,25-dihydroxyvatimin D3 (1,25(OH)2D3), 26,26,26,27,27, 27-hexafluoro-1,25-dihydroxyvitamin D3 (26,27-F6-1,25-(OH)2D3) has been compared with 1,25(OH)2D3 as to its biological activity in vitamin D-deficient chicks. One day old, white Leghorn cockerels were fed a rachitogenic diet for 5 weeks. They were then given vehicle or 32.5, 130 or 325 pmol of 26,27-F6-1,25(OH)2D3 or 1,25(OH)2D3 in a solution of propylenglycol:ethanol (95:5 v/v) sc every day for 2 weeks. Twenty-four hours after the last dose, the animals were sacrificed and their femurs were removed. 26,27-F6-1,25(OH)2D3 was more active than 1,25(OH)2D3 in stimulating growth, healing of rachitic cartilage visualized by soft X-ray radiography, elevation of serum inorganic phosphorus, and mineralization of rachitic bone. These biological differences between two compounds were observed only for the dose of 130 pmol. However, this fluorinated compound has less binding ability than 1,25(OH)2D3 to fetal chick intestinal cytosol receptors. The mechanism of the higher potency of this analogue is still unknown, but its affinity to the 1,25(OH)2D3 receptor does not account for the higher activity. Since 26-hydroxylation can be postulated as the inactivation step in vitamin D metabolism, these results suggest that the reason for increased activity of this fluorinated analogue is most likely its slower metabolism.

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