Effects of depleted uranium after short-term exposure on vitamin D metabolism in rat.
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 D(3) 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 D(3)-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.
Tissandie
E
E
Radiobiology and Epidemiology Department, Laboratory of Experimental Toxicology, Institute for Radiological Protection and Nuclear Safety, 92262 Fontenay-aux-Roses Cedex, France.
Guéguen
Y
Y
Lobaccaro
J M A
JM
Paquet
F
F
Aigueperse
J
J
Souidi
M
M
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014501:Uranium / Q000633:toxicity*; D014807:Vitamin D / Q000378:metabolism*
D012333:RNA, Messenger; D014807:Vitamin D; D014501:Uranium; D003577:Cytochrome P-450 Enzyme System