title: Influence of 25-hydroxyvitamin D3and 1,25-dihydroxyvitamin D3on expression of P-glycoprotein and cytochrome P450 3A in sheep.
abstract: In order to improve calcium and phosphorus balance, beef cattle and dairy cows can be supplemented with vitamin D. However, different vitamin D metabolites have been shown to increase expression of P-glycoprotein (P-gp, MDR1, ABCB1) and cytochrome P450 3A (CYP3A) in rodents as well as in cell culture systems. As such interferences might have an impact on pharmacokinetics of some drugs widely-used in veterinary medicine, we investigated the expression of P-gp, CYP3A, vitamin D receptor (VDR), pregnane X receptor (PXR) and retinoid X receptor α (RXRα) in sheep either treated orally with 6μg/kg body weight (BW) 25-hydroxyvitamin D3(OHD3) for ten days before sacrifice or 12h after intravenous injection of 0.5μg/kg BW 1,25-dihydroxyvitamin D3(1,25- (OH)2D3). Down-regulation of ruminal, jejunal and hepatic, but not renal P-gp could be found with 25-OHD3supplementation. Interestingly, this effect on P-gp was not observed in tissues from 1,25-(OH)2D3-treated sheep. In contrast, 1,25-(OH)2D3induced a significant up-regulation of renal and jejunal CYP3A expression, while 25-OHD3had no impact. Renal expression of VDR and PXR was also increased by treatment with 1,25-(OH)2D3, while jejunal PXR expression was only stimulated in sheep supplemented with 25-OHD3. Either treatments increased renal, but not ruminal, jejunal or hepatic expression of RXRα. These results demonstrate that the impact of large doses of vitamin D metabolites on different target organs and potential interactions with other medications should be further investigated in vitro and in vivo to understand the effects of vitamin D metabolites on metabolism and excretion pathways in livestock.
authors: Department of Physiology, University of Veterinary Medicine Hannover, Foundation, 30173 Hannover, Germany. Electronic address: Mirja.Wilkens@tiho-hannover.de.
authors: M R
authors: MR
authors: Wilkens
authors: Laboratory of Veterinary Pharmacology, Center of Veterinary Research (CIVETAN, CONICET) Faculty of Veterinary Sciences, UNCPBA, B7000 Tandil, Argentina.
authors: L M
authors: LM
authors: Maté
authors: Department of Physiology, University of Veterinary Medicine Hannover, Foundation, 30173 Hannover, Germany.
authors: N
authors: N
authors: Schnepel
authors: Department of Physiology, University of Veterinary Medicine Hannover, Foundation, 30173 Hannover, Germany.
authors: S
authors: S
authors: Klinger
authors: Department of Physiology, University of Veterinary Medicine Hannover, Foundation, 30173 Hannover, Germany.
authors: A S
authors: AS
authors: Muscher-Banse
authors: Laboratory of Veterinary Pharmacology, Center of Veterinary Research (CIVETAN, CONICET) Faculty of Veterinary Sciences, UNCPBA, B7000 Tandil, Argentina.
authors: M
authors: M
authors: Ballent
authors: Laboratory of Veterinary Pharmacology, Center of Veterinary Research (CIVETAN, CONICET) Faculty of Veterinary Sciences, UNCPBA, B7000 Tandil, Argentina.
authors: G
authors: G
authors: Virkel
authors: Laboratory of Veterinary Pharmacology, Center of Veterinary Research (CIVETAN, CONICET) Faculty of Veterinary Sciences, UNCPBA, B7000 Tandil, Argentina.
authors: A L
authors: AL
authors: Lifschitz
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D002112:Calcifediol / Q000494:pharmacology*; D002117:Calcitriol / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007275:Injections, Intravenous; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism; D047490:Retinoid X Receptor alpha / Q000235:genetics / Q000378:metabolism; D012417:Rumen / Q000187:drug effects / Q000378:metabolism; D034561:Sheep, Domestic
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D047490:Retinoid X Receptor alpha; D051544:Cytochrome P-450 CYP3A; D002117:Calcitriol; D002112:Calcifediol
keywords: ABCB1; Cholecalciferol; MDR1; Pharmacological interaction; Ruminant