First Author | Deluca HF | Year | 2011 |
Journal | Arch Biochem Biophys | Volume | 505 |
Issue | 2 | Pages | 226-30 |
PubMed ID | 20965147 | Mgi Jnum | J:169265 |
Mgi Id | MGI:4940169 | Doi | 10.1016/j.abb.2010.10.012 |
Citation | Deluca HF, et al. (2011) 1,25-Dihydroxyvitamin D is not responsible for toxicity caused by vitamin D or 25-hydroxyvitamin D. Arch Biochem Biophys 505(2):226-30 |
abstractText | Vitamin D intoxication was produced with oral doses of either vitamin D or 25-hydroxyvitamin D in CYP27B1 -/- (1alpha-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 400-700 ng/ml or 1000-1750 nM in the serum of both groups of mice. Toxicity was evidenced by severe hypercalcemia and weight loss. Measurement of 1,25-dihydroxyvitamin D in serum confirmed its absence from serum of the CYP27B1 -/- mice given 25-hydroxyvitamin D. 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. |