Administration of Vitamin D Metabolites Affects RNA Expression of Xenobiotic Metabolising Enzymes and Function of ABC Transporters in Rats
- Autores
- Klumpp, Karoline; Lange, Frauke; Muscher-Banse, Alexandra S.; Schnepel, Nadine; Hansen, Kathrin; Lifschitz, Adrian Luis; Maté, María Laura; Wilkens, Mirja
- Año de publicación
- 2019
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- From studies on different species and in cell culture systems, it has been suggested that vitamin D metabolites might affect themetabolism and elimination of xenobiotics. Although most studies performed on rodents and cell cultures report an upregulationof respective enzymes and transporters, data from the literature are inconsistent. Especially results obtained with sheep differ fromthese observations. As vitamin D metabolites are widely used as feed additives or therapeutics in livestock animals, we aimed toassess whether these differences indicate species-specific responses or occurred due to the very high dosages used in the rodentstudies. -erefore, we applied treatment protocols to rats that had been used previously in sheep or cattle. Forty-eight female ratswere divided into three treatment and corresponding placebo groups: (1) a single intraperitoneal injection of 1,25-(OH)2D3 orplacebo 12 h before sacrifice; (2) daily supplementation with 25-OHD3 by oral gavage or placebo for 10 days; and (3) a singleintramuscular injection of vitamin D3 10 days before sacrifice. In contrast to a previous study using sheep, treatment of rats with1,25-dihydroxyvitamin D3 did not result in an upregulation of cytochrome P450 3A isoenzymes (CYP3A), but a decrease wasfound in hepatic and intestinal expressions. In addition, a downregulation of P-glycoprotein (P-gp) and breast cancer resistanceprotein was found in the brain. Taken together, the stimulating effects of vitamin D metabolites on the expression of genesinvolved in the metabolism and elimination of xenobiotics reported previously for rodents and sheep could not be reproduced. Incontrast, we even observed a negative impact on the expression of CYP3A enzymes and their most important regulator, thepregnane X receptor. Most interestingly, we could demonstrate an effect of treatment with 25-hydroxyvitamin D3 and vitamin D3on the functional activity of ileal P-glycoprotein (P-gp) using the Ussing chamber technique.
Fil: Klumpp, Karoline. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; Alemania
Fil: Lange, Frauke. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; Alemania
Fil: Muscher-Banse, Alexandra S.. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; Alemania
Fil: Schnepel, Nadine. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; Alemania
Fil: Hansen, Kathrin. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; Alemania
Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Maté, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Wilkens, Mirja. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; Alemania - Materia
-
VITAMIN D
XENOBIOTICS
TRANSPORTERS - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/105299
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Administration of Vitamin D Metabolites Affects RNA Expression of Xenobiotic Metabolising Enzymes and Function of ABC Transporters in RatsKlumpp, KarolineLange, FraukeMuscher-Banse, Alexandra S.Schnepel, NadineHansen, KathrinLifschitz, Adrian LuisMaté, María LauraWilkens, MirjaVITAMIN DXENOBIOTICSTRANSPORTERShttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3https://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4From studies on different species and in cell culture systems, it has been suggested that vitamin D metabolites might affect themetabolism and elimination of xenobiotics. Although most studies performed on rodents and cell cultures report an upregulationof respective enzymes and transporters, data from the literature are inconsistent. Especially results obtained with sheep differ fromthese observations. As vitamin D metabolites are widely used as feed additives or therapeutics in livestock animals, we aimed toassess whether these differences indicate species-specific responses or occurred due to the very high dosages used in the rodentstudies. -erefore, we applied treatment protocols to rats that had been used previously in sheep or cattle. Forty-eight female ratswere divided into three treatment and corresponding placebo groups: (1) a single intraperitoneal injection of 1,25-(OH)2D3 orplacebo 12 h before sacrifice; (2) daily supplementation with 25-OHD3 by oral gavage or placebo for 10 days; and (3) a singleintramuscular injection of vitamin D3 10 days before sacrifice. In contrast to a previous study using sheep, treatment of rats with1,25-dihydroxyvitamin D3 did not result in an upregulation of cytochrome P450 3A isoenzymes (CYP3A), but a decrease wasfound in hepatic and intestinal expressions. In addition, a downregulation of P-glycoprotein (P-gp) and breast cancer resistanceprotein was found in the brain. Taken together, the stimulating effects of vitamin D metabolites on the expression of genesinvolved in the metabolism and elimination of xenobiotics reported previously for rodents and sheep could not be reproduced. Incontrast, we even observed a negative impact on the expression of CYP3A enzymes and their most important regulator, thepregnane X receptor. Most interestingly, we could demonstrate an effect of treatment with 25-hydroxyvitamin D3 and vitamin D3on the functional activity of ileal P-glycoprotein (P-gp) using the Ussing chamber technique.Fil: Klumpp, Karoline. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; AlemaniaFil: Lange, Frauke. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; AlemaniaFil: Muscher-Banse, Alexandra S.. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; AlemaniaFil: Schnepel, Nadine. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; AlemaniaFil: Hansen, Kathrin. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; AlemaniaFil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Maté, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Wilkens, Mirja. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; AlemaniaHindawi Publishing Corporation2019-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/105299Klumpp, Karoline; Lange, Frauke; Muscher-Banse, Alexandra S.; Schnepel, Nadine; Hansen, Kathrin; et al.; Administration of Vitamin D Metabolites Affects RNA Expression of Xenobiotic Metabolising Enzymes and Function of ABC Transporters in Rats; Hindawi Publishing Corporation; Journal of Chemistry; 2019; 10-2019; 1-112090-9071CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.hindawi.com/journals/jchem/2019/1279036/info:eu-repo/semantics/altIdentifier/doi/10.1155/2019/1279036info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:30:38Zoai:ri.conicet.gov.ar:11336/105299instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:30:38.582CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Administration of Vitamin D Metabolites Affects RNA Expression of Xenobiotic Metabolising Enzymes and Function of ABC Transporters in Rats |
title |
Administration of Vitamin D Metabolites Affects RNA Expression of Xenobiotic Metabolising Enzymes and Function of ABC Transporters in Rats |
spellingShingle |
Administration of Vitamin D Metabolites Affects RNA Expression of Xenobiotic Metabolising Enzymes and Function of ABC Transporters in Rats Klumpp, Karoline VITAMIN D XENOBIOTICS TRANSPORTERS |
title_short |
Administration of Vitamin D Metabolites Affects RNA Expression of Xenobiotic Metabolising Enzymes and Function of ABC Transporters in Rats |
title_full |
Administration of Vitamin D Metabolites Affects RNA Expression of Xenobiotic Metabolising Enzymes and Function of ABC Transporters in Rats |
title_fullStr |
Administration of Vitamin D Metabolites Affects RNA Expression of Xenobiotic Metabolising Enzymes and Function of ABC Transporters in Rats |
title_full_unstemmed |
Administration of Vitamin D Metabolites Affects RNA Expression of Xenobiotic Metabolising Enzymes and Function of ABC Transporters in Rats |
title_sort |
Administration of Vitamin D Metabolites Affects RNA Expression of Xenobiotic Metabolising Enzymes and Function of ABC Transporters in Rats |
dc.creator.none.fl_str_mv |
Klumpp, Karoline Lange, Frauke Muscher-Banse, Alexandra S. Schnepel, Nadine Hansen, Kathrin Lifschitz, Adrian Luis Maté, María Laura Wilkens, Mirja |
author |
Klumpp, Karoline |
author_facet |
Klumpp, Karoline Lange, Frauke Muscher-Banse, Alexandra S. Schnepel, Nadine Hansen, Kathrin Lifschitz, Adrian Luis Maté, María Laura Wilkens, Mirja |
author_role |
author |
author2 |
Lange, Frauke Muscher-Banse, Alexandra S. Schnepel, Nadine Hansen, Kathrin Lifschitz, Adrian Luis Maté, María Laura Wilkens, Mirja |
author2_role |
author author author author author author author |
dc.subject.none.fl_str_mv |
VITAMIN D XENOBIOTICS TRANSPORTERS |
topic |
VITAMIN D XENOBIOTICS TRANSPORTERS |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.3 https://purl.org/becyt/ford/3 https://purl.org/becyt/ford/4.3 https://purl.org/becyt/ford/4 |
dc.description.none.fl_txt_mv |
From studies on different species and in cell culture systems, it has been suggested that vitamin D metabolites might affect themetabolism and elimination of xenobiotics. Although most studies performed on rodents and cell cultures report an upregulationof respective enzymes and transporters, data from the literature are inconsistent. Especially results obtained with sheep differ fromthese observations. As vitamin D metabolites are widely used as feed additives or therapeutics in livestock animals, we aimed toassess whether these differences indicate species-specific responses or occurred due to the very high dosages used in the rodentstudies. -erefore, we applied treatment protocols to rats that had been used previously in sheep or cattle. Forty-eight female ratswere divided into three treatment and corresponding placebo groups: (1) a single intraperitoneal injection of 1,25-(OH)2D3 orplacebo 12 h before sacrifice; (2) daily supplementation with 25-OHD3 by oral gavage or placebo for 10 days; and (3) a singleintramuscular injection of vitamin D3 10 days before sacrifice. In contrast to a previous study using sheep, treatment of rats with1,25-dihydroxyvitamin D3 did not result in an upregulation of cytochrome P450 3A isoenzymes (CYP3A), but a decrease wasfound in hepatic and intestinal expressions. In addition, a downregulation of P-glycoprotein (P-gp) and breast cancer resistanceprotein was found in the brain. Taken together, the stimulating effects of vitamin D metabolites on the expression of genesinvolved in the metabolism and elimination of xenobiotics reported previously for rodents and sheep could not be reproduced. Incontrast, we even observed a negative impact on the expression of CYP3A enzymes and their most important regulator, thepregnane X receptor. Most interestingly, we could demonstrate an effect of treatment with 25-hydroxyvitamin D3 and vitamin D3on the functional activity of ileal P-glycoprotein (P-gp) using the Ussing chamber technique. Fil: Klumpp, Karoline. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; Alemania Fil: Lange, Frauke. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; Alemania Fil: Muscher-Banse, Alexandra S.. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; Alemania Fil: Schnepel, Nadine. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; Alemania Fil: Hansen, Kathrin. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; Alemania Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina Fil: Maté, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina Fil: Wilkens, Mirja. University of Veterinary Medicine Hannover. Institute of Physiology and Cell Biology; Alemania |
description |
From studies on different species and in cell culture systems, it has been suggested that vitamin D metabolites might affect themetabolism and elimination of xenobiotics. Although most studies performed on rodents and cell cultures report an upregulationof respective enzymes and transporters, data from the literature are inconsistent. Especially results obtained with sheep differ fromthese observations. As vitamin D metabolites are widely used as feed additives or therapeutics in livestock animals, we aimed toassess whether these differences indicate species-specific responses or occurred due to the very high dosages used in the rodentstudies. -erefore, we applied treatment protocols to rats that had been used previously in sheep or cattle. Forty-eight female ratswere divided into three treatment and corresponding placebo groups: (1) a single intraperitoneal injection of 1,25-(OH)2D3 orplacebo 12 h before sacrifice; (2) daily supplementation with 25-OHD3 by oral gavage or placebo for 10 days; and (3) a singleintramuscular injection of vitamin D3 10 days before sacrifice. In contrast to a previous study using sheep, treatment of rats with1,25-dihydroxyvitamin D3 did not result in an upregulation of cytochrome P450 3A isoenzymes (CYP3A), but a decrease wasfound in hepatic and intestinal expressions. In addition, a downregulation of P-glycoprotein (P-gp) and breast cancer resistanceprotein was found in the brain. Taken together, the stimulating effects of vitamin D metabolites on the expression of genesinvolved in the metabolism and elimination of xenobiotics reported previously for rodents and sheep could not be reproduced. Incontrast, we even observed a negative impact on the expression of CYP3A enzymes and their most important regulator, thepregnane X receptor. Most interestingly, we could demonstrate an effect of treatment with 25-hydroxyvitamin D3 and vitamin D3on the functional activity of ileal P-glycoprotein (P-gp) using the Ussing chamber technique. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-10 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/105299 Klumpp, Karoline; Lange, Frauke; Muscher-Banse, Alexandra S.; Schnepel, Nadine; Hansen, Kathrin; et al.; Administration of Vitamin D Metabolites Affects RNA Expression of Xenobiotic Metabolising Enzymes and Function of ABC Transporters in Rats; Hindawi Publishing Corporation; Journal of Chemistry; 2019; 10-2019; 1-11 2090-9071 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/105299 |
identifier_str_mv |
Klumpp, Karoline; Lange, Frauke; Muscher-Banse, Alexandra S.; Schnepel, Nadine; Hansen, Kathrin; et al.; Administration of Vitamin D Metabolites Affects RNA Expression of Xenobiotic Metabolising Enzymes and Function of ABC Transporters in Rats; Hindawi Publishing Corporation; Journal of Chemistry; 2019; 10-2019; 1-11 2090-9071 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://www.hindawi.com/journals/jchem/2019/1279036/ info:eu-repo/semantics/altIdentifier/doi/10.1155/2019/1279036 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Hindawi Publishing Corporation |
publisher.none.fl_str_mv |
Hindawi Publishing Corporation |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1844614315063115776 |
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13.070432 |