A Novel Rat Model of Vitamin D Deficiency: Safe and Rapid Induction of Vitamin D and Calcitriol Deficiency without Hyperparathyroidism
BioMed Research International, 2015, Article ID 604275, 5 pages, http://dx.doi.org/10.1155/2015/604275
Andrea W. D. Stavenuiter,1 Maria Vittoria Arcidiacono,2 Evelina Ferrantelli,1 Eelco D. Keuning,1 Marc Vila Cuenca,1 Piet M. ter Wee,3 Robert H. J. Beelen,1 Marc G. Vervloet,3 and Adriana S. Dusso2
1Department of Molecular Cell Biology & Immunology, VU University Medical Center, 1081 BT Amsterdam, Netherlands
2Division of Experimental Nephrology, IRBLleida, 25198 Lleida, Spain
3Department of Nephrology, VU University Medical Center, 1007 MB Amsterdam, Netherlands
Vitamin D deficiency is associated with a range of clinical disorders. To study the mechanisms involved and improve treatments, animal models are tremendously useful. Current vitamin D deficient rat models have important practical limitations, including time requirements when using, exclusively, a vitamin D deficient diet. More importantly, induction of hypovitaminosis D causes significant fluctuations in parathyroid hormone (PTH) and mineral levels, complicating the interpretation of study results. To overcome these shortcomings, we report the successful induction of vitamin D deficiency within three weeks, with stable serum PTH and minerals levels, in Wistar rats. We incorporated two additional manoeuvres compared to a conventional diet. Firstly, the vitamin D depleted diet is calcium (Ca) enriched, to attenuate the development of secondary hyperparathyroidism. Secondly, six intraperitoneal injections of paricalcitol during the first two weeks are given to induce the rapid degradation of circulating vitamin D metabolites. After three weeks, serum 25-hydroxyvitamin D3 (25D) and 1,25-dihydroxyvitamin D3 (1,25D) levels had dropped below detection limits, with unchanged serum PTH, Ca, and phosphate (P) levels. Therefore, this model provides a useful tool to examine the sole effect of hypovitaminosis D, in a wide range of research settings, without confounding changes in PTH, Ca, and P.
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Paricalcitol is a selective vitamin D receptor (VDR) activator,
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