Plasma Levels of Vitamin D Metabolites in Diphosphonatetreated Rats

1981 ◽  
Vol 61 (4) ◽  
pp. 471-476 ◽  
Author(s):  
U. Trechsel ◽  
C. M. Taylor ◽  
J. A. Eisman ◽  
J.-P. Bonjour ◽  
H. Fleisch

1. Protein-binding assays have been used to measure plasma 1,25-dihydroxy-vitamin D [1,25-(OH)2D] as well as 25-hydroxy-vitamin D [25-(OH)D] in rats given 10 mg of phosphorus (P) day−1 kg−1 as ethane-1-hydroxy-1,1-diphosphonate (EHDP). 2. In control animals given a normal laboratory chow plasma 25-(OH)D and 1,25-(OH)2D were about 40 nmol/l and 300 pmol/l respectively. 3. EHDP produced a decrease of plasma 1,25-(OH)2D to below 50 pmol/l in 2 days. 4. Both in control and in EHDP-treated rats plasma 1,25-(OH)2D increased when dietary calcium (Ca) was restricted to 0.1%, or dietary P to 0.2%, indicating that the well-known stimulatory effect of Ca or P deprivation was at least partially effective in EHDP-treated rats. 5. In response to an increase of the oral supply of vitamin D3 to 65 nmol/day the plasma level of 25-(OH)D rose in both control and EHDP groups. Plasma 1,25-(OH)2D was not increased above the normal value in control rats. In EHDP-treated rats, however, plasma 1,25-(OH)2D rose to a level equal to that in controls, suggesting that the effect of EHDP on plasma 1,25-(OH)2D can be overcome at high precursor concentration.

1978 ◽  
Vol 24 (2) ◽  
pp. 287-298 ◽  
Author(s):  
G Jones

Abstract I describe a new assay that is capable of measuring vitamin D2, vitamin D3, 25-hydroxyvitamin D2, and 25-hydroxyvitamin D3 in 2 ml of plasma or serum. Plasma is extracted by the Bligh and Dyer technique [Can. J. Biochem. Physiol. 37, 911 (1959)], the lipid component is fractionated by two high-performance liquid-chromatographic systems based upon adsorption and reversed-phase chromatography, and each of the four vitamin D metabolites is measured by its absorbance at 254 nm. The method has a sensitivity limit of 0.5 mug/liter of plasma. The identity of metabolite peaks was confirmed by mass spectrometry, ultraviolet absorption spectrophotometry, and rechromatography, and there was good correlation (r=0.84) between plasma 25-hydroxyvitamin D as measured by the present method and by a protein binding assay developed in our laboratory. Mean concentrations of vitamin D and 25-hydroxyvitamin D in normal adults (n=25) in December were 2.2 +/- 1.1 (SD) and 16 +/- 3.9 (SD) mug/liter, respectively. 25-Hyroxyvitamin D2 made up 31% of the total 25-hydroxyvitamin D. Patients receiving pharmacological doses of vitamin D had values for vitamin D and 25-hydroxyvitamin D that were 10- to 100-fold normal. This method provides a rapid, reliable physico-chemical assay that appears to have advantages over existing protein binding assays and can be used to measure circulating vitamin D.


1985 ◽  
Vol 40 (1-2) ◽  
pp. 102-108 ◽  
Author(s):  
Ana R. de Boland ◽  
Ricardo Boland

Cultures of vitamin D-deficient chick soleus muscle and 12 day-old chick embryo myoblasts were used to characterize the effects of 1,25-dihydroxy-vitamin D3 and 25-hydroxy-vitamin D3 on muscle cell Ca metabolism. Physiological amounts of both sterols increased the rate and extent of 45Ca uptake by cultures. However. 1.25(OH)2D3 was significantly more effective than 25 OHD3. The greater potency of 1,25(OH)2D3 to increase Ca uptake could be shown after various treatment intervals of cultures and using a wide concentration range of both derivatives. Information about Ca pools affected by vitamin D3 metabolites was obtained through kinetic analysis of Ca efflux in cultured myoblasts. Cytoplasmic and mitochondria Ca pools were identified on the basis of their half-times of desaturation and by selective inhibition of plasma membrane and mitochondrial Ca transport with LaCl3 and Ruthenium Red, respectively. The data suggests that 1,25(OH)2D3 acts on muscle cellular Ca by increasing Ca efflux and influx through mitochondrial and plasma membranes whereas the predominant effect of 25 OHD3 is to increase Ca influx into mitochondria.


Author(s):  
Teodora-Irina Adam-Bonci ◽  
Paraschiva Cherecheș-Panța ◽  
Eduard-Alexandru Bonci ◽  
Sorin Claudiu Man ◽  
Ancuța Cutaș-Benedec ◽  
...  

Even though vitamin D is widely acknowledged as having a potential immunomodulatory role in asthma, its exact beneficial mechanisms are yet to be clarified. An optimal serum 25-hydroxy-vitamin D (25-OH-VitD) level in pediatric asthma patients might not rely solely on the effect of dose-dependent vitamin D3 intake, but might also be influenced by factors related to insufficient asthma control. We aimed to survey the prevalence of serum 25-OH-VitD deficiency and analyze whether suboptimal levels were associated with asthma severity factors. The current cross-sectional study enrolled 131 pediatric asthma or asthma-suggestive recurrent wheezing patients, for whom serum 25-OH-VitD, IgE, and eosinophil count were assessed. The prevalence of suboptimal serum 25-OH-VitD was 58.8%. A suboptimal vitamin D status was associated with asthma exacerbation in the previous month (p = 0.02). Even under seasonal oral vitamin D3 supplementation, patients with a positive history of asthma attack in the previous four weeks presented significantly lower serum 25-OH-VitD concentrations, compared to their peers with no disease exacerbation. In conclusion, sequential measurements of serum 25-OH-VitD might prove useful for future studies evaluating the dynamic changes in vitamin D3 status in regard to asthma, especially in symptomatic patients.


2019 ◽  
Vol 44 (5) ◽  
pp. 575-577
Author(s):  
Yasemin Benderli Cihan

AbstractVitamin D is known as the bone hormone, it is also know that it has effects on cancer because of its anti-inflammatory and immunomodulatory characteristics and its effects on cytokine levels. It is seen that vitamin D use together with radiotherapy can have a positive effect on cancer treatment. It should be investigated whether toxicities due to radiation is prevented by vitamin D metabolites’ increasing the induction of immunomodulator cells and the capacities of immune response cells. Use of 1,25[OH]2 Vitamin D3 analogs as an adjuvant immunomodulator for patients receiving radiotherapy should be evaluated. There is a need for studies to be done in this regard.


1983 ◽  
Vol 245 (4) ◽  
pp. E359-E364 ◽  
Author(s):  
G. S. Reddy ◽  
G. Jones ◽  
S. W. Kooh ◽  
D. Fraser ◽  
H. F. DeLuca

Previously we have shown that the isolated perfused kidney from vitamin D-deficient rats converts [3H]25(OH)D3 into [3H]1 alpha,25(OH)2D3. When certain vitamin D metabolites were added to perfusate the same kidney began to synthesize [3H]24R,25(OH)2D3. In this study we investigated the structural requirements of the vitamin D molecule necessary to stimulate synthesis of [3H]24R,25(OH)2D3 in a 1-hydroxylating kidney. Kidneys were perfused with tracer [3H]25(OH)D3 (450 pM) alone and in the presence of a variety of hydroxylated metabolites and fluorinated analogues of vitamin D3 at concentrations of 450 pM to 25 microM. Tracer [3H]25(OH)D3 alone resulted in synthesis of only [3H]1 alpha,25(OH)2D3 during the 6-h perfusion period. 25-Hydroxylated metabolites [25(OH)D3, 25 nM; 1 alpha,25(OH)2D3, 25 nM; 24R,25(OH)2D3, 25 nM; 24(F)2,25(OH)D3, 50 nM] stimulated [3H]24R,25(OH)2D3 production at 2 h of perfusion. On the other hand, analogues without the 25-hydroxyl group [D3; 1 alpha(OH)D3; 25(F)D3; 1 alpha(OH),25(F)D3; 1 alpha(F)D3; 1 beta(F)D3]; did not stimulate [3H]24R,25(OH)2D3 synthesis. We conclude that the 25-hydroxyl group is an essential determinant of 24-hydroxylation.


2017 ◽  
Vol 35 ◽  
pp. e284
Author(s):  
G. Colussi ◽  
C. Catena ◽  
L. Driul ◽  
A. Rossi ◽  
V. Fagotto ◽  
...  

2019 ◽  
Vol 3 (7) ◽  
Author(s):  
Xueyan Fu ◽  
Gregory G Dolnikowski ◽  
William B Patterson ◽  
Bess Dawson-Hughes ◽  
Tong Zheng ◽  
...  

ABSTRACTBackgroundLow serum total 25-hydroxyvitamin D3 [25(OH)D3] concentrations have been associated with cognitive impairment. However, it is unclear if serum 25(OH)D3 concentrations are a valid indicator of the concentrations of vitamin D and its metabolites in human brain.ObjectivesThe aim of this study was to develop and validate a method to quantify vitamin D3, 25(OH)D3, and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in human brain.MethodsThe assay developments were performed using porcine brains. Liquid extraction was used in homogenized samples (∼0.1 g each) prior to analysis by LC-MS/MS with electrospray ionization following derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione. This method was then applied to the determination of vitamin D and its metabolites in a whole human brain obtained from the National Development and Research Institutes.ResultsThe method showed good linearity of vitamin D3, 25(OH)D3, and 1,25(OH)2D3 over the physiological range (R2 = 0.9995, 0.9968, and 0.9970, respectively). The lowest detection limit for vitamin D3, 25(OH)D3, and 1,25(OH)2D3 in porcine brain was 25, 50 and 25 pg/g, respectively. The method was successfully applied to the determination of vitamin D3 and its metabolites in the prefrontal cortex, middle frontal cortex, middle temporal cortex, cerebellum, corpus callosum, medulla, and pons of a human brain. All analyzed human brain regions contained 25(OH)D3, with corpus callosum containing 334 pg/g compared with 158 pg/g in cerebellum. 1,25(OH)2D3 was only detected in prefrontal and middle frontal cortices at a very low level. No vitamin D3 was detected in any examined areas of this single human brain.ConclusionsTo the best of our knowledge, this study is the first report of the measurement of concentrations of vitamin D metabolites in human brain. This validated method can be applied to postmortem studies to obtain accurate information about the presence and role of vitamin D and its metabolites in human brain and neurodegenerative diseases.


1983 ◽  
Vol 244 (6) ◽  
pp. F674-F678 ◽  
Author(s):  
M. M. Friedlaender ◽  
Z. Kornberg ◽  
H. Wald ◽  
M. M. Popovtzer

The effects of 1 alpha (OH)vitamin D3 [1 alpha (OH)D3] and 24,25(OH)2vitamin D3 [24,25(OH)2D3] on the phosphaturic action of parathyroid hormone (PTH) were studied in two groups of parathyroidectomized (PTX) rats. In group 1, PTX PTH-infused rats received intravenous 1 alpha (OH)D3, and in group 2, PTX PTH-infused rats received intravenous 24,25(OH)2D3. PTX PTH-infused rats served as controls. The effects of both vitamin D metabolites on renal PTH-activated adenylate cyclase (AC) were studied in vitro. In group 1, PTH increased fractional excretion of phosphate (CP/CIn) from 0.045 +/- 0.012 (+/- SE) to 0.263 +/- 0.011 (P less than 0.005). 1 alpha (OH)D3 failed to influence this response. In group 2, PTH increased CP/CIn from 0.055 +/- 0.008 to 0.289 +/- 0.027 (P less than 0.005). 24,25(OH)2D3 reduced the PTH-induced rise in CP/CIn from 0.289 +/- 0.027 to 0.192 +/- 0.021 (P less than 0.01) and decreased the urinary excretion of adenosine 3',5'-cyclic monophosphate. In vitro, 24,25(OH)2D3 blunted the PTH-activated AC, whereas 1 alpha (OH)D3 had no effect. These results show that 24,25(OH)D3, similar to two other 25(OH) metabolites of vitamin D-25(OH)vitamin D3 and 1,25(OH)2vitamin D3-suppresses the phosphaturic action of PTH, whereas 1 alpha(OH)D3, which is devoid of a 25(OH) group, lacks this effect. This suggests that a 25(OH) group is a prerequisite for the antiphosphaturic effect of vitamin D, whereas the 1 alpha (OH) group is not essential for this action.


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