Phenobarbital suppresses vitamin D3 25-hydroxylase expression: A potential new mechanism for drug-induced osteomalacia
Section snippets
Materials and methods
Materials. The expression plasmid for the human retinoid X receptor α (RXRα) was a kind gift from Dr. Ronald M. Evans, Howard Hughes Medical Institute, The Salk Institute for Biological Studies, San Diego, CA. The expression plasmids for the human pregnane X receptor (PXR) and constitutive androstane receptor (CAR) and the empty vector pCR3 were gifts from Dr. Masahiko Negishi, Laboratory of Reproductive and Developmental Toxicology, NIEHS, NIH, Research Triangle Park, NC. 1α-Hydroxyvitamin D3
Phenobarbital inhibits vitamin D3 25-hydroxylase activity in primary hepatocytes
Primary porcine hepatocytes treated with phenobarbital (1.5 mM) for 48 h were incubated with 1α-hydroxyvitamin D3. HPLC analysis of the cell culture medium showed that phenobarbital inhibited the rate of 25-hydroxylation by about 70% (Table 1).
Effects of phenobarbital on the expression of CYP2D25 and CYP27A1 mRNA in primary hepatocytes
Experiments were carried out to study the effects of phenobarbital on mRNA levels of two hepatic 25-hydroxylases, the microsomal CYP2D25 and mitochondrial CYP27A1. The isolated hepatocytes were separately treated with phenobarbital for 6, 12, or 48 h and RNA
Acknowledgments
This work was supported by the Swedish Research Council-Medicine (project 03X-218) and the Novo Nordisk Foundation.
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