Thiabendazole Is an Inducer of Cytochrome P4501A1 in Cultured Rabbit Hepatocytes

Aix, L.; Rey-Grobellet, X; Larrieu, G.; Lesca, P.; Galtier, P.

doi:10.1006/bbrc.1994.2098

Cited by 56 publications

(32 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous compounds have been reported to induce Cyp1a1 that do not seem to compete with TCDD for binding to the AhR, including thiazolium compounds, retinoids, carotenoids, benzimidazoles, carbamates, and aminoquinoline (Daujat et al, 1992;Aix et al, 1994;Lesca et al, 1995;Gradelet et al, 1997;Ledirac et al, 1997;Fontaine et al, 1999). Although the lack of in vitro AhR binding for the many Cyp1a1 inducers may result from technical limitations of the binding assays Denison and Nagy, 2003), it has also been suggested that many of these com- pounds may induce Cyp1a1 through multiple modes of indirect AhR activation.…”

Section: Discussionmentioning

confidence: 99%

Induction of Cyp1a1 Is a Nonspecific Biomarker of Aryl Hydrocarbon Receptor Activation: Results of Large Scale Screening of Pharmaceuticals and Toxicants in Vivo and in Vitro

Hu¹,

et al. 2007

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Induction of Cyp1a1 Is a Nonspecific Biomarker of Aryl Hydrocarbon Receptor Activation: Results of Large Scale Screening of Pharmaceuticals and Toxicants in Vivo and in Vitro

Hu¹,

et al. 2007

View full text Add to dashboard Cite

“…TBZ is extensively metabolized via hydroxylation of the benzimidazole (BZ) ring at the 5-positition to form 5-hydroxythiabendazole, which is further metabolized to glucuronide and sulfate conjugates [10,11]. TBZ induces the expression of CYP families CYP1A and CYP2B in rats in vivo [12] and rabbit CYP1A2 in vitro [13]. Members of CYP1A and CYP2B families in mammals are regulated by the nuclear hormone receptors (NHRs), pregnane X receptor (PXR) and constitutive androstane receptor (CAR) [14].…”

Section: Introductionmentioning

confidence: 99%

NHR-176 regulates cyp-35d1 to control hydroxylation-dependent metabolism of thiabendazole in Caenorhabditis elegans

Jones

Flemming

Urwin

2015

Biochemical Journal

View full text Add to dashboard Cite

Knowledge of how drugs are metabolized and excreted is an essential component of understanding their fate within and among target and non-target organisms. Thiabendazole (TBZ) was the first benzimidazole (BZ) to be commercially available and remains one of the most important anthelmintic drugs for medical and veterinary use. We have characterized how Caenorhabditis elegans metabolizes and excretes TBZ. We have shown that TBZ directly binds to the nuclear hormone receptor (NHR)-176 and that this receptor is required for the induction by TBZ of the cytochrome P450 (CYP) encoded by cyp-35d1. Further, RNAi inhibition of cyp-35d1 in animals exposed to TBZ causes a reduction in the quantity of a hydroxylated TBZ metabolite and its glucose conjugate that is detected in C. elegans tissue by HPLC. This final metabolite is unique to nematodes and we also identify two P-glycoproteins (PGPs) necessary for its excretion. Finally, we have shown that inhibiting the metabolism we describe increases the susceptibility of C. elegans to TBZ in wild-type and in resistant genetic backgrounds.

show abstract

“…Until now, AHR-mediated transcriptional activity represented by the transcriptional activity of CYP1A1, whose promoter contains XRE, has been applied as a screening procedure for AHR-activating compounds (Garrison et al 1996;Natsume et al 2005;Hamada et al 2006). However, the AHR-mediated transcriptional activity does not necessarily correspond to the transcriptional activity of CYP1A1 (Aix et al 1994;Denison et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Establishment of a stable aryl hydrocarbon receptor-responsive HepG2 cell line

Satsu

Yoshida²,

Mikubo

et al. 2014

Cytotechnology

View full text Add to dashboard Cite

The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor. It heterodimerizes with aryl hydrocarbon nuclear translocator, binds to the xenobiotic-responsive element (XRE), and enhances the transcription of genes encoding xenobiotic metabolizing enzymes. AHR also plays important roles in the inhibition of intestinal carcinogenesis and the modulation of gut immunity. It is very important to screen for AHR-activating compounds because those are expected to produce the AHR-mediated physiological functions. Until now, AHR-mediated transcriptional activity represented by the transcriptional activity of CYP1A1 in luciferase assay has been applied as a screening procedure for AHR-activating compounds. However, the AHR-mediated transcriptional activity did not necessarily correspond with the CYP1A1 transcriptional activity. To evaluate AHRmediated transcriptional activity more specifically, and to screen for AHR-activating compounds, we establish a stable AHR-responsive HepG2 cell line by co-transfection of an AHR expression vector and an AHR-responsive vector (pGL3-XRE) containing a luciferase gene and three tandemly arranged XRE elements into a human hepatoma derived cell line, HepG2. The induction of luciferase activity in the stable AHR-responsive HepG2 cell line by typical AHR activators occurred in time-and concentrationdependent manners. By assessing the AHR target genes CYP1A1, UGT1A1, and ABCG2, an AHR activator-mediated induction was observed at mRNA level. Furthermore, the AHR activator-mediated induction of luciferase activity was positively correlated with the mRNA levels of CYP1A1, UGT1A1, and ABCG2. These findings verified the usefulness of the established stable AHR-responsive HepG2 cell line for the screening of AHR-activating compounds.

show abstract

Thiabendazole Is an Inducer of Cytochrome P4501A1 in Cultured Rabbit Hepatocytes

Cited by 56 publications

References 0 publications

Induction of Cyp1a1 Is a Nonspecific Biomarker of Aryl Hydrocarbon Receptor Activation: Results of Large Scale Screening of Pharmaceuticals and Toxicants in Vivo and in Vitro

Induction of Cyp1a1 Is a Nonspecific Biomarker of Aryl Hydrocarbon Receptor Activation: Results of Large Scale Screening of Pharmaceuticals and Toxicants in Vivo and in Vitro

NHR-176 regulates cyp-35d1 to control hydroxylation-dependent metabolism of thiabendazole in Caenorhabditis elegans

Establishment of a stable aryl hydrocarbon receptor-responsive HepG2 cell line

Contact Info

Product

Resources

About