Effects of depleted uranium after short-term exposure on vitamin D metabolism in rat
Résumé
Uranium is a natural radioactive heavy metal. Its toxicity has been demonstrated for different organs, including bone, kidney, liver and brain. Effects of an acute contamination by depleted uranium (DU) were investigated in vivo on vitamin D3 biosynthetic pathway. Rats received an intragastric administration of DU (204 mg/kg) and various parameters were studied either on day 1 or day 3 after contamination. Cytochrome P450 (CYP27A1, CYP2R1, CYP27B1, CYP24A1) enzymes involved in vitamin D metabolism and two vitamin D3-target genes (ECaC1, CaBP-D9K) were assessed by real time RT-PCR in liver and kidneys. CYP27A1 activity was measured in liver and vitamin D and parathyroid hormone (PTH) level were measured in plasma. In acute treated-rats, vitamin D level was increased by 62% and decreased by 68% in plasma, respectively at day 1 and at day 3, which paralleled with a concomitant decrease of PTH level (90%) at day 3. In liver, cyp2r1 mRNA level was increased at day 3. Cyp27a1 activity decreased at day 1 and increased markedly at day 3. In kidney, cyp27b1 mRNA was increased at days 1 and 3 (11- and 4-fold respectively). Moreover, ecac1 and cabp-d9k mRNA levels were increased at day 1 and decreased at day 3. This work shows for the first time that DU acute contamination modulates both activity and expression of CYP enzymes involved in vitamin D metabolism in liver and kidney, and consequently affects vitamin D target genes levels. © Springer-Verlag 2006.
Mots clés
kidney
liver
liver mitochondrion
male
nonhuman
parathyroid hormone blood level
priority journal
radiation exposure
rat
real time polymerase chain reaction
reverse transcription polymerase chain reaction
vitamin D metabolism
Animals
Cytochrome P-450 Enzyme System
Gene Expression Regulation
Enzymologic
Kidney
Liver
Male
Rats
Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
RNA
Messenger
Uranium
Vitamin D
2 hydroxypropyl beta cyclodextrin
calcium channel
carbon 14
cholesterol
colecalciferol
cytochrome P450
messenger RNA
parathyroid hormone
sterol 27 hydroxylase
uranium
uranyl nitrate
vitamin D
animal experiment
article
controlled study
enzyme activity
gene expression