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See detailCYP1A1 induction and CYP3A4 inhibition by the fungicide imazalil in the human intestinal Caco-2 cells-Comparison with other conazole pesticides
Sergent, Thérèse; Dupont, Isabelle; Jassogne, Coralie et al

in Toxicology Letters (2009), 184(3), 159-168

Imazalil (IMA) is a widely used imidazole-antifungal pesticide and. therefore. a food contaminant. This compound is also used as a drug (enilconazole). As intestine is the first site of exposure to ... [more ▼]

Imazalil (IMA) is a widely used imidazole-antifungal pesticide and. therefore. a food contaminant. This compound is also used as a drug (enilconazole). As intestine is the first site of exposure to ingested drugs and pollutants, we have investigated the effects of IMA, at realistic intestinal concentrations, on xenobiotic-metabolizing enzymes and efflux pumps by using Caco-2 cells, as a validated in vitro model of the human intestinal absorptive epithelium. For comparison, other conazole fungicides, i.e. ketoconazole, propiconazole and tebuconazole. were also studied. IMA induced cytochrome P450 (CYP) 1A1 activity to the same extent as benzo(a)pyrene (B(a)P) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in a dose-and time-dependent manner. Cell-free aryl hydrocarbon receptor (AhR) binding assay and reporter gene assay suggested that IMA is not an AhR-ligand, implying that IMA-mediated induction should involve an AhR-independent pathway. Moreover, IMA strongly inhibited the CYP3A4 activity in 1,25-vitamin D-3-induced Caco-2 cells. The other fungicides had weak or nil effects on CYP activities. Study of the apical efflux pump activities revealed that ketoconazole inhibited both P-glycoprotein (Pgp) and multidrug resistance-associated protein 2 (MRP-2) or breast cancer resistance protein (BCRP), whereas IMA and other fungicides did not. Our results imply that coingestion of IMA-contaminated food and CYP3A4- or CYP1A1-metabolizable drugs or chemicals could lead to drug bioavailability modulation or toxicological interactions, with possible adverse effects for human health. (C) 2008 Elsevier Ireland Ltd. All rights reserved. [less ▲]

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See detailFood flavonoid aryl hydrocarbon receptor-mediated agonistic/antagonistic/synergic activities in human and rat reporter gene assays
Van Der Heiden, Edwige ULg; Bechoux, Nathalie ULg; Muller, Marc ULg et al

in Analytica Chimica Acta (2009), 637

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor mediating the adverse effects of dioxins and polycyclic aromatic hydrocarbons (PAHs). In this study, we investigated the genetic ... [more ▼]

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor mediating the adverse effects of dioxins and polycyclic aromatic hydrocarbons (PAHs). In this study, we investigated the genetic-, time-, dose-, species- and tissue-dependent AhR-mediated agonistic/ antagonistic activities of three food flavonoids: quercetin, chrysin and genistein. To that end, four stably transfected cell lines were used in cell-based luciferase reporter gene assays: three lines were transformed with the ptKLuc vector harbouring four dioxinresponsive elements (DREs) upstream of the thymidine kinase promoter and the luciferase gene (HepG2-Luc, T-47D-Luc and H4IIE-ULg). The fourth is a patented cell line transformed with a different construct: H4IIE DR-CALUX®. Both H4IIE cells were compared for their genetic construction. Human hepatoma (HepG2-Luc) and human breast tumour (T-47D-Luc) cells were compared for tissue-dependent effects. Rat hepatoma (H4IIE-ULg) and human hepatoma (HepG2-Luc) cellswere compared for species-dependent activities.We concluded that quercetin, chrysin and genistein act in a time-, dose-, species- and tissue-specific way. For example, genistein displayed agonistic activities when exposed to rat hepatoma cells during 6h but not after 24 h. Flavonoids displayed agonistic/antagonistic activities in human breast tumour cells, depending on the exposure time, while in human hepatoma cells, only antagonistic activities of flavonoids were measured. In addition, we report, in all the cells, a synergy between an isoflavone and two food contaminants; the 2,3,7,8-tetrachlorodibenzop- dioxin and 3-methylcholanthrene, a PAH. In rat cells, this synergy occurred when cells were exposed to flavonoids and contaminant for 6h, while it was observed in human cells only after 24 h. [less ▲]

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See detailDetection of glucocorticoid bioactivity in bovine urine samples using a reporter gene assay
Connolly, Lisa; Cai, Kai; Van Der Heiden, Edwige ULg et al

in Analytica Chimica Acta (2009), 637

The illegal use of anabolic substances in the meat producing industry is an ongoing problem due to the continual production of new synthetic compounds and/or the practice of lowlevel cocktail ... [more ▼]

The illegal use of anabolic substances in the meat producing industry is an ongoing problem due to the continual production of new synthetic compounds and/or the practice of lowlevel cocktail administration to avoid detection by the surveillance schemes of EU member states National Plan surveillance systems. We present a highly sensitive reporter gene assay and sample extraction procedure based on a two step solid phase extraction and high performance liquid chromatography, developed for the detection of glucocorticoid abuse in bovine urine. The assay is capable of detecting compounds with glucocorticoid bioactivity and is extremely sensitive with an EC50 of 0.79 ngmL−1 for dexamethasone. New or unknown compounds with glucocorticoid bioactivity and low-level cocktail mixtures are detectable by this assay. Cross-reactivity data for a range of 11 -hydroxyglucocorticoids has been provided. This assay shows low interference from the 11-keto prohormones and other steroidal hormones. The assay may be suitable for application in other matrices such as hair. In conclusion this screening assay offers advantages over existing analytical techniques. [less ▲]

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See detailTime-, species- and tissue-dependent activity profiles of food flavonoids on the activation of the aryl hydrocarbon pathway
Van Der Heiden, Edwige ULg; Bechoux, Nathalie ULg; Sergent, Thérèse et al

in van Ginkel, L. A.; Bergwerff, A. A. (Eds.) Residues of Veterinary Drugs in Foods, Proceedings of the Euroresidue VI Conference (2008, May 19)

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See detailDetection of glucocorticoid bioactivity in bovine urine samples using a reporter gene assay
Connolly, Lisa; Kai, C.; Van Der Heiden, Edwige ULg et al

in Proceedings of the Euroresidue VI Conference (2008)

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See detailImazalil modulates CYPs 1A1 and 3A4 activities in the human Caco-2 cells as an intestinal model to assess food safety
Sergent, Thérèse; Ribonnet, Laurence; Jassogne, C. et al

in Toxicology Letters (2007), 172

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See detailNew experimental approach of identification and characterization of emerging risks in food safety (EMRISK).
Ribonnet, Laurence; Sergent, Thérèse; Nobels, Ingrid et al

Report (2007)

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See detailStudy of the flavonoids effect on the AhR-dependent transcription using reporter gene assays
Van Der Heiden, Edwige ULg; Bechoux, Nathalie ULg; Sergent, Thérèse et al

in Journal of Biotechnology (2007), 131(2, Suppl. S), 6

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See detailSet up of an experimental tool in order to investigate food chemical contaminant toxicity at realistic concentrations
Ribonnet, Laurence; Sergent, Thérèse; Nobels, Ingrid et al

in Toxicology Letters (2007), 172

Detailed reference viewed: 25 (6 ULg)