Influence of 25-HYDROXYVITAMIN D3(25-OHD3) and 1,25-DIHYDROXYVITAMIN D3(1,25-(OH)2D3) on expression of P-glycoprotein (P-GP) and Cytochrome P450 3A (CYP3A) in sheep

WILKENS M.; MATÉ L.; SCHNEPEL N; KLINGER C.; MUSCHER-BANSE A.S; BALLENT M.; VIRKEL G.; LIFSCHITZ A.

Delft

Workshop; 18th Workshop on Vitamin D; 2015

Inordertoimprovecalciumandphosphorusbalanceaswellasmeatqualitybeefcattleanddairycowscanbesupplementedwith25-OHD3.However,vitaminDmetaboliteshavebeenshowntoincreaseexpressionofP-glycoprotein(P-gp)andcytochromeP4503A(CYP3A)inrodents(1,2). TheATP-driveneffluxpumpP-gpplaysacrucialroleintissuedistributionandexcretionofalargeamountofxenobiotics.MostofthemundergoCYP3Amediatedtransformationbeforetheycanbeextrudedfromdifferentcelltypes.Both,P-gpandCYP3A,areregulatedbynuclearreceptors,afamilyincludingthevitaminDreceptor(VDR)andthepregnaneXreceptor(PXR).IthasbeenshownthathydroxylatedvitaminDmetabolitescanalsobindtohumanPXR(3). Assuchinterferencesmighthaveanimpactonpharmacokineticsofsomedrugswidely-usedinveterinarymedicine,weinvestigatedtheexpressionofP-gp,CYP3A,VDR,PXRandtheco-receptorassociatedwithboth,VDRandPXR,theretinoidXreceptoralpha(RXRα)insheepeithertreatedwitheither25-OHD3or1,25-(OH)2D3,respectively.