Administration of Vitamin D Metabolites Affects RNA Expression of Xenobiotic Metabolising Enzymes and Function of ABC Transporters in Rats
From studies on different species and in cell culture systems, it has been suggested that vitamin D metabolites might affect the metabolism and elimination of xenobiotics. Although most studies performed on rodents and cell cultures report an upregulation of respective enzymes and transporters, data...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2019/1279036 |
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| author | Karoline Klumpp Frauke Lange Alexandra S. Muscher-Banse Nadine Schnepel Kathrin Hansen Adrian L. Lifschitz Laura Mate Mirja R. Wilkens |
| author_facet | Karoline Klumpp Frauke Lange Alexandra S. Muscher-Banse Nadine Schnepel Kathrin Hansen Adrian L. Lifschitz Laura Mate Mirja R. Wilkens |
| author_sort | Karoline Klumpp |
| collection | DOAJ |
| description | From studies on different species and in cell culture systems, it has been suggested that vitamin D metabolites might affect the metabolism and elimination of xenobiotics. Although most studies performed on rodents and cell cultures report an upregulation of respective enzymes and transporters, data from the literature are inconsistent. Especially results obtained with sheep differ from these observations. As vitamin D metabolites are widely used as feed additives or therapeutics in livestock animals, we aimed to assess whether these differences indicate species-specific responses or occurred due to the very high dosages used in the rodent studies. Therefore, we applied treatment protocols to rats that had been used previously in sheep or cattle. Forty-eight female rats were divided into three treatment and corresponding placebo groups: (1) a single intraperitoneal injection of 1,25-(OH)2D3 or placebo 12 h before sacrifice; (2) daily supplementation with 25-OHD3 by oral gavage or placebo for 10 days; and (3) a single intramuscular injection of vitamin D3 10 days before sacrifice. In contrast to a previous study using sheep, treatment of rats with 1,25-dihydroxyvitamin D3 did not result in an upregulation of cytochrome P450 3A isoenzymes (CYP3A), but a decrease was found in hepatic and intestinal expressions. In addition, a downregulation of P-glycoprotein (P-gp) and breast cancer resistance protein was found in the brain. Taken together, the stimulating effects of vitamin D metabolites on the expression of genes involved in the metabolism and elimination of xenobiotics reported previously for rodents and sheep could not be reproduced. In contrast, we even observed a negative impact on the expression of CYP3A enzymes and their most important regulator, the pregnane X receptor. Most interestingly, we could demonstrate an effect of treatment with 25-hydroxyvitamin D3 and vitamin D3 on the functional activity of ileal P-glycoprotein (P-gp) using the Ussing chamber technique. |
| format | Article |
| id | doaj-art-e04958d4a9a7472b88e336d8fccb9f64 |
| institution | Kabale University |
| issn | 2090-9063 2090-9071 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Chemistry |
| spelling | doaj-art-e04958d4a9a7472b88e336d8fccb9f642025-02-03T05:59:02ZengWileyJournal of Chemistry2090-90632090-90712019-01-01201910.1155/2019/12790361279036Administration of Vitamin D Metabolites Affects RNA Expression of Xenobiotic Metabolising Enzymes and Function of ABC Transporters in RatsKaroline Klumpp0Frauke Lange1Alexandra S. Muscher-Banse2Nadine Schnepel3Kathrin Hansen4Adrian L. Lifschitz5Laura Mate6Mirja R. Wilkens7Institute of Physiology and Cell Biology, University of Veterinary Medicine Hannover, Hanover, GermanyInstitute of Physiology and Cell Biology, University of Veterinary Medicine Hannover, Hanover, GermanyInstitute of Physiology and Cell Biology, University of Veterinary Medicine Hannover, Hanover, GermanyInstitute of Physiology and Cell Biology, University of Veterinary Medicine Hannover, Hanover, GermanyInstitute of Physiology and Cell Biology, University of Veterinary Medicine Hannover, Hanover, GermanyLaboratory of Veterinary Pharmacology, Faculty of Veterinary Sciences, National University of Central Buenos Aires Province, B7000 Tandil, ArgentinaLaboratory of Veterinary Pharmacology, Faculty of Veterinary Sciences, National University of Central Buenos Aires Province, B7000 Tandil, ArgentinaInstitute of Physiology and Cell Biology, University of Veterinary Medicine Hannover, Hanover, GermanyFrom studies on different species and in cell culture systems, it has been suggested that vitamin D metabolites might affect the metabolism and elimination of xenobiotics. Although most studies performed on rodents and cell cultures report an upregulation of respective enzymes and transporters, data from the literature are inconsistent. Especially results obtained with sheep differ from these observations. As vitamin D metabolites are widely used as feed additives or therapeutics in livestock animals, we aimed to assess whether these differences indicate species-specific responses or occurred due to the very high dosages used in the rodent studies. Therefore, we applied treatment protocols to rats that had been used previously in sheep or cattle. Forty-eight female rats were divided into three treatment and corresponding placebo groups: (1) a single intraperitoneal injection of 1,25-(OH)2D3 or placebo 12 h before sacrifice; (2) daily supplementation with 25-OHD3 by oral gavage or placebo for 10 days; and (3) a single intramuscular injection of vitamin D3 10 days before sacrifice. In contrast to a previous study using sheep, treatment of rats with 1,25-dihydroxyvitamin D3 did not result in an upregulation of cytochrome P450 3A isoenzymes (CYP3A), but a decrease was found in hepatic and intestinal expressions. In addition, a downregulation of P-glycoprotein (P-gp) and breast cancer resistance protein was found in the brain. Taken together, the stimulating effects of vitamin D metabolites on the expression of genes involved in the metabolism and elimination of xenobiotics reported previously for rodents and sheep could not be reproduced. In contrast, we even observed a negative impact on the expression of CYP3A enzymes and their most important regulator, the pregnane X receptor. Most interestingly, we could demonstrate an effect of treatment with 25-hydroxyvitamin D3 and vitamin D3 on the functional activity of ileal P-glycoprotein (P-gp) using the Ussing chamber technique.http://dx.doi.org/10.1155/2019/1279036 |
| spellingShingle | Karoline Klumpp Frauke Lange Alexandra S. Muscher-Banse Nadine Schnepel Kathrin Hansen Adrian L. Lifschitz Laura Mate Mirja R. Wilkens Administration of Vitamin D Metabolites Affects RNA Expression of Xenobiotic Metabolising Enzymes and Function of ABC Transporters in Rats Journal of Chemistry |
| title | 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_short | 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 |
| url | http://dx.doi.org/10.1155/2019/1279036 |
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