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Fipronil induces CYP isoforms in rats

dc.contributor.authorCaballero, Juan Luis
dc.contributor.authorAres Lombán, Irma
dc.contributor.authorMartínez Caballero, Marta
dc.contributor.authorMartínez Larrañaga, María Rosa
dc.contributor.authorAnadón Navarro, Arturo Ramón
dc.contributor.authorMartínez Caballero, María Aranzazu
dc.date.accessioned2024-02-01T13:49:38Z
dc.date.available2024-02-01T13:49:38Z
dc.date.issued2015
dc.description.abstractThe goal of the present study was to evaluate fipronil effects on the activities of drug metabolizing enzymes in rat liver microsomes. Rats were orally treated with fipronil at doses of 1, 5, 10 and 15 mg/kg bw/day for 6 days. Determinations of cytochrome P450 (CYP) enzyme activities were carried out in hepatic microsomes isolated from treated rats. The activities of some members of CYP2E, CYP1A, CYP2A, CYP2B and CYP3A subfamilies significantly increased after fipronil treatment in a dose-dependent manner as compared to control. The major effects were observed in the O-deethylation of ethoxyresorufin and O-demethylation of methoxyresorufin (reflecting CYP1A1/2 activities), in the O-depenthylation of pentoxyresorufin and 16β-hydroxylation of testosterone (reflecting CYP2B1/2 activities), and in the N-demethylation of erythromycin and 6β-hydroxylation of testosterone (reflecting CYP3A1/2 activities). Immunoblot studies revealed that fipronil increased the apoprotein levels of CYP1A1. Our results suggest that fipronil is an inducer of hepatic phase I CYP enzymes, causing an increased potential to interact with a wide range of xenobiotics or endogenous chemicals that are substrates of the CYP1A, CYP2B and CYP3A subfamilies. Further investigations are required to in vivo evaluate the potential of the metabolite fipronil sulfone as an inducer of phase I CYP enzymes
dc.description.departmentDepto. de Farmacología y Toxicología
dc.description.facultyFac. de Veterinaria
dc.description.refereedTRUE
dc.description.sponsorshipUniversidad Complutense de Madrid
dc.description.sponsorshipComunidad de Madrid
dc.description.statuspub
dc.identifier.citationCaballero MV, Ares I, Martínez M, Martínez-Larrañaga MR, Anadón A, Martínez MA. Fipronil induces CYP isoforms in rats. Food Chem Toxicol. 2015 Sep;83:215-21. doi: 10.1016/j.fct.2015.06.019. Epub 2015 Jul 2. PMID: 26142839.
dc.identifier.doi10.1016/j.fct.2015.06.019
dc.identifier.issn0278-6915
dc.identifier.officialurlhttps://doi.org/10.1016/j.fct.2015.06.019
dc.identifier.pmid26142839
dc.identifier.urihttps://hdl.handle.net/20.500.14352/97780
dc.journal.titleFood and Chemical Toxicology
dc.language.isoeng
dc.page.final221
dc.page.initial215
dc.publisherElsevier
dc.rights.accessRightsrestricted access
dc.subject.cdu636.09
dc.subject.cdu613.2.099
dc.subject.keywordFipronil
dc.subject.keywordCytochrome P450 enzymes
dc.subject.keywordHepatic microsomes
dc.subject.keywordRats
dc.subject.ucmVeterinaria
dc.subject.unesco3214 Toxicología
dc.titleFipronil induces CYP isoforms in rats
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number83
dspace.entity.typePublication
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relation.isAuthorOfPublication.latestForDiscovery38ae9baa-ab95-45a3-9183-9861451b2c1a

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