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

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.

1974 ◽  
Vol 46 (4) ◽  
pp. 433-448 ◽  
Author(s):  
J. Silver ◽  
G. Neale ◽  
G. R. Thompson

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.


1978 ◽  
Vol 174 (1) ◽  
pp. 231-236 ◽  
Author(s):  
E Spanos ◽  
D I Barrett ◽  
K T Chong ◽  
I MacIntyre

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.


1972 ◽  
Vol 43 (3) ◽  
pp. 413-431 ◽  
Author(s):  
E. Barbara Mawer ◽  
Joan Backhouse ◽  
Carlene A. Holman ◽  
G. A. Lumb ◽  
S. W. Stanbury

1. The distribution of vitamin D and its metabolites in human tissues has been studied by the combined use of radioactive cholecalciferol and biological assays of antiricketic activity in tissue extracts. 2. Injected radioactive cholecalciferol was cleared rapidly from the blood; unchanged vitamin D and various metabolites were detected subsequently in all tissues examined. The highest concentration of biological activity and radioactivity was in fat; this and, to a lesser extent, other tissues were shown to retain activity over a prolonged period of time. 3. Adipose tissue and voluntary muscle are the principal sites of storage of vitamin D in man. Pre-existing tissue pools of vitamin D can, in some circumstances, invalidate the use of radioactively labelled cholecalciferol to trace the pattern of body distribution. 4. Metabolically produced 25-hydroxycholecalciferol is also taken up from the blood into many tissues, probably by protein-binding. 5. Vitamin D is excreted in bile principally as more polar metabolites. Smaller amounts of cholecalciferol and 25-hydroxycholecalciferol are also excreted, and antiricketic activity has been demonstrated in the bile of individuals treated with vitamin D. 6. An excess of cholecalciferol (or of 25-hydroxycholecalciferol) in the blood appears to be eliminated by the physicochemical processes of partition into tissue lipid and binding to tissue proteins. It is inferred tentatively that an increased concentration of vitamin D or of 25-hydroxycholecalciferol in the liver also causes an increased biliary excretion of these substances, and an increased hepatic formation and elimination of more polar metabolites of the vitamin.


Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2780
Author(s):  
Andrzej Krajewski ◽  
Krzysztof Piorun ◽  
Dominika Maciejewska-Markiewicz ◽  
Marta Markowska ◽  
Karolina Skonieczna-Żydecka ◽  
...  

Background: Burned patients have an increased need for vitamin D supply related to the maintenance of calcium–phosphate homeostasis and the regulation of cell proliferation/differentiation. This study aimed to analyze the concentration of 25-hydroxycholecalciferol and its relationship with severe condition after burn injury. Methods: 126 patients were enrolled in the study. Patients were qualified due to thermal burns—over 10% of total body surface area. On the day of admission, the following parameters were assessed: 25-hydroxycholecalciferol concentration, total protein concentration, albumin concentration, aspartate transaminase activity, alanine transaminase activity, albumin concentration, creatinine concentration, c-reactive protein concentration, procalcitonin concentration, and interleukin-6 concentration. Results: Almost all patients (92%) in the study group had an improper level of vitamin D (<30 ng/mL), with the average of 11.6 ± 10.7 ng/mL; 17.5% of patients had levels of vitamin D below the limit of determination—under 3 ng/mL. The study showed that there are several factors which correlated with vitamin D concentration during the acute phase of burn injury, including: total protein (r = 0.42, p < 0.01), albumin, (r = 0.62, p < 0.01), percentage of body burns (r = 0.36, p < 0.05), aspartate aminotransferase (r = 0.21, p < 0.05), and c-reactive protein (r = 0.22, p < 0.05). We did not find any significant correlation between vitamin D concentration and body mass index. Conclusions: The burn injury has an enormous impact on the metabolism and the risk factors of the deficiency for the general population (BMI) have an effect on burned patients. Our study showed that concentration of 25-hydroxycholecalciferol is strongly correlated with serum albumin level, even more than total burn surface area and burn degrees as expected. We suspect that increased supplementation of vitamin D should be based on albumin level and last until albumin levels are balanced.


2021 ◽  
Vol 10 (3) ◽  
pp. 526
Author(s):  
Jakub Kwiatek ◽  
Aleksandra Jaroń ◽  
Grzegorz Trybek

Introduction: The most important factor which is responsible for the positive course of implant treatment is the process of osseointegration between the implant structure and the host’s bone tissue. The aim of this study was to assess what effect the 25-hydroxycholecalciferol concentration and vitamin D deficiency treatment have on changes in the bone level at the implant site during the process of osseointegration in the mandible. Materials and Methods: The study was with 122 people qualified for implant surgery, who were assigned to three research groups (A, B, and C). Laboratory, clinical, and radiological tests were performed on the day of surgery, and after 6 and 12 weeks. The bone level in the immediate proximity of the implant was determined by radiovisiography (RVG). Results: The bone level after 12 weeks in Groups B and C was significantly higher than after 6 weeks. The bone level in the study Group B was significantly higher than in Group A. The study showed that the higher the levels of 25-hydroxycholecalciferol were observed on the day of surgery, the higher was the level of bone surrounding the implant after 6 and 12 after surgery. Conclusion: The correct level of 25-hydroxycholecalciferol on the day of surgery and vitamin D deficiency treatment significantly increase the bone level at the implant site in the process of radiologically assessed osseointegration.


1971 ◽  
Vol 121 (4) ◽  
pp. 673-682 ◽  
Author(s):  
D. E. M. Lawson ◽  
B. Pelc ◽  
P. A. Bell ◽  
P. W. Wilson ◽  
E. Kodicek

[1,2-3H2]Cholecalciferol has been synthesized with a specific radioactivity of 508mCi/mmol by using tristriphenylphosphinerhodium chloride, the homogeneous hydrogen catalyst. With doses of 125ng (5i.u.) of [4-14C,1-3H2]cholecalciferol the tissue distribution in rachitic rats of cholecalciferol and its metabolites (25-hydroxycholecalciferol and peak P material) was similar to that found in chicken with 500ng doses of the double-labelled vitamin. The only exceptions were rat kidney, with a very high concentration of vitamin D, and rat blood, with a higher proportion of peak P material, containing a substance formed from vitamin D with the loss of hydrogen from C-1. Substance P formed from [4-14C,1,2-3H2]cholecalciferol retained 36% of 3H, the amount expected from its distribution between C-1 and C-2, the 3H at C-1 being lost. 25-Hydroxycholecalciferol does not seem to have any specific intracellular localization within the intestine of rachitic chicks. The 3H-deficient substance P was present in the intestine and bone 1h after a dose of vitamin D and 30min after 25-hydroxycholecalciferol. There was very little 25-hydroxycholecalciferol in intestine at any time-interval, but bone and blood continued to take it up over the 8h experimental period. It is suggested that the intestinal 3H-deficient substance P originates from outside this tissue. The polar metabolite found in blood and which has retained its 3H at C-1 is not a precursor of the intestinal 3H-deficient substance P.


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