1,25-Dihydroxyvitamin D is not responsible for toxicity caused by vitamin D or 25-hydroxyvitamin D

► 1,25-Dihydroxyvitamin D is not responsible for vitamin D intoxication. ► 25-Hydroxyvitamin D is likely responsible for vitamin D3 intoxication. ► CYP27B1 deletion does not reduce or enhance vitamin D intoxication. Vitamin D intoxication was produced with oral doses of either vitamin D3 or 25-hydro...

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Bibliographic Details
Published in:Archives of biochemistry and biophysics 2011-01, Vol.505 (2), p.226-230
Main Authors: DeLuca, Hector F., Prahl, Jean M., Plum, Lori A.
Format: Article
Language:English
Subjects:
25-Hydroxyvitamin D
25-Hydroxyvitamin D3 1-alpha-Hydroxylase - deficiency
25-Hydroxyvitamin D3 1-alpha-Hydroxylase - genetics
Animals
Body Weight - drug effects
Calcifediol - blood
Calcifediol - metabolism
Calcifediol - toxicity
Calcitriol
Calcitriol - blood
Calcitriol - metabolism
Calcitriol - toxicity
Calcium
Gene Knockout Techniques
Hypercalcemia
Hypervitaminosis D
Intoxication
Male
Mice
Toxicity
Transcription
Transcription, Genetic - drug effects
Vitamin D - blood
Vitamin D - metabolism
Vitamin D - toxicity
Vitamin D metabolites
Vitamin D receptors
Vitamin D3
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Summary:► 1,25-Dihydroxyvitamin D is not responsible for vitamin D intoxication. ► 25-Hydroxyvitamin D is likely responsible for vitamin D3 intoxication. ► CYP27B1 deletion does not reduce or enhance vitamin D intoxication. Vitamin D intoxication was produced with oral doses of either vitamin D3 or 25-hydroxyvitamin D3 in CYP27B1 −/− (1α-hydroxylase knockout) and wild-type mice. These compounds were equally toxic in wild-type and the mutant mice. Since the null mutant mice are unable to produce 1,25-dihydroxyvitamin D, it is clear 1,25-dihydroxyvitamin D is not responsible for vitamin D intoxication. On the other hand, 25-hydroxyvitamin D rises to levels of 400–700ng/ml or 1000–1750nM in the serum of both groups of mice. Toxicity was evidenced by severe hypercalcemia and weight loss. Measurement of 1,25-dihydroxyvitamin D3 in serum confirmed its absence from serum of the CYP27B1 −/− mice given 25-hydroxyvitamin D3. Since high concentrations of 25-hydroxyvitamin D can bind the vitamin D receptor and can induce transcription, 25-hydroxyvitamin D is likely responsible for toxicity of vitamin D excess.
ISSN:0003-9861
1096-0384
DOI:10.1016/j.abb.2010.10.012