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Changes in cytochrome P450 gene expression and enzyme activity induced by xenobiotics in rabbits in vivo and in vitro

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Changes in cytochrome P450 gene expression and enzyme activity induced by xenobiotics in rabbits in vivo and in vitro

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dc.contributor.author Palócz, Orsolya es_ES
dc.contributor.author Farkas, Orsolya es_ES
dc.contributor.author Clayton, Paul es_ES
dc.contributor.author Csikó, György es_ES
dc.date.accessioned 2017-07-10T09:58:18Z
dc.date.available 2017-07-10T09:58:18Z
dc.date.issued 2017-06-28
dc.identifier.issn 1257-5011
dc.identifier.uri http://hdl.handle.net/10251/84831
dc.description.abstract [EN] As considerable inter-species differences exist in xenobiotic metabolism, developing new pharmaceutical therapies for use in different species is fraught with difficulties. For this reason, very few medicines have been registered for use in rabbits, despite their importance in inter alia meat and fur production. We have developed a rapid and sensitive screening system for drug safety in rabbits based on cytochrome P450 enzyme assays, specifically CYP1A1, CYP1A2 and CYP3A6, employing an adaptation of the luciferin-based clinical assay currently used in human drug screening. Short-term (4-h) cultured rabbit primary hepatocytes were treated with a cytochrome inducer (phenobarbital) and 2 inhibitors (alpha-naphthoflavone and ketoconazole). In parallel, and to provide verification, New Zealand white rabbits were dosed with 80 mg/kg phenobarbital or 40 mg/kg ketoconazole for 3 d. Ketoconazole significantly increased CYP3A6 gene expression and decreased CYP3A6 activity both in vitro and in vivo. CYP1A1 activity was decreased by ketoconazole in vitro and increased in vivo. This is the first report of the inducer effect of ketoconazole on rabbit cytochrome isoenzymes in vivo. Our data support the use of a luciferin-based assay in short-term primary hepatocytes as an appropriate tool for xenobiotic metabolism assays and short-term toxicity testing in rabbits. es_ES
dc.description.sponsorship The study was supported by the Research Faculty Grant 2014 of the Szent István University, Faculty of Veterinary Science (grant no. KK-UK-15266), and by the Hungarian Scientific Research Found (OTKA 105718). We are grateful to Department of Biochemistry, Eötvös Loránd University for enable to use their Beckman L7-65 Ultracentrifuge.
dc.language Inglés es_ES
dc.publisher Universitat Politècnica de València
dc.relation.ispartof World Rabbit Science
dc.rights Reserva de todos los derechos es_ES
dc.subject CYP450 es_ES
dc.subject Hepatocyte es_ES
dc.subject Ketoconazole es_ES
dc.subject Luminescence es_ES
dc.subject Rabbit es_ES
dc.title Changes in cytochrome P450 gene expression and enzyme activity induced by xenobiotics in rabbits in vivo and in vitro es_ES
dc.type Artículo es_ES
dc.date.updated 2017-07-10T07:28:07Z
dc.identifier.doi 10.4995/wrs.2017.4574
dc.relation.projectID info:eu-repo/grantAgreement/OTKA//105718/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/SZIU//KK-UK-15266/
dc.rights.accessRights Abierto es_ES
dc.description.bibliographicCitation Palócz, O.; Farkas, O.; Clayton, P.; Csikó, G. (2017). Changes in cytochrome P450 gene expression and enzyme activity induced by xenobiotics in rabbits in vivo and in vitro. World Rabbit Science. 25(2):173-180. https://doi.org/10.4995/wrs.2017.4574 es_ES
dc.description.accrualMethod SWORD es_ES
dc.relation.publisherversion https://doi.org/10.4995/wrs.2017.4574 es_ES
dc.description.upvformatpinicio 173 es_ES
dc.description.upvformatpfin 180 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 25
dc.description.issue 2
dc.identifier.eissn 1989-8886
dc.contributor.funder Szent István University, Hungría
dc.contributor.funder Hungarian Scientific Research Fund


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