Structural Requirements for the Induction of Cytochromes P450 by Benzimidazole Anthelmintic Derivatives in Cultured Rabbit Hepatocytes

Rey-Grobellet, X; Ferré, Nathalie; Eeckhoutte, C.; Larrieu, G.; Pineau, Thierry; Galtier, P.

doi:10.1006/bbrc.1996.0482

Cited by 20 publications

(11 citation statements)

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“…1) The P450 induction responses in the chick model were qualitatively and quantitatively similar to those reported in mammalian species. Thus, a strong mixed CYP1A and CYP2 induction for benzylimidazole and a weaker mixed induction for omeprazole and thiabendazole, selective induction of CYP1A by albendazole, and scanty effects for benzimidazole were also reported in mammalian liver (Papac and Franklin, 1988;Souhaili-el Amri et al, 1988;Curi-Pedrosa et al, 1994;Rey-Grobellet et al, 1996;Masubuchi et al, 1997;Price et al, 2004). Although in the chick model, omeprazole did not produce the high CYP1A induction seen in human liver cells, omeprazole, in particular, has shown species differences in CYP1A induction (Kikuchi et al, 1996).…”

Section: Discussionmentioning

confidence: 97%

“…1) on hepatic P450-dependent AA metabolism in the chick embryo model. The compounds studied included several reported to induce CYP1A alone or together with CYP2 enzymes in mammalian liver or cultured cells: albendazole, benzylimidazole, omeprazole, and thiabendazole (Papac and Franklin, 1988;Souhaili-el Amri et al, 1988;Aix et al, 1994;Curi-Pedrosa et al, 1994;Rey-Grobellet et al, 1996;Price et al, 2004). In addition, we examined the effect of a third-generation aromatase inhibitor, the triazole derivative vorozole (De Coster et al, 1990;Goss, 1998) for which reports of P450-inducing activities were not found.…”

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confidence: 99%

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Induction of Cyp1a and Cyp2-Mediated Arachidonic Acid Epoxygenation and Suppression of 20-Hydroxyeicosatetraenoic Acid by Imidazole Derivatives Including the Aromatase Inhibitor Vorozole

Diani-Moore¹,

Papachristou²,

Labitzke³

et al. 2006

Drug Metab Dispos

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ABSTRACT:Cytochrome P450 (P450) enzymes metabolize the membrane lipid arachidonic acid to stable biologically active epoxides [eicosatrienoic acids (EETs)] and 20-hydroxyeicosatetraenoic acid (20-HETE). These products have cardiovascular activity, primarily acting as vasodilators and vasoconstrictors, respectively. EET formation can be increased by the prototype CYP1A or CYP2 inducers, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or phenobarbital (PB), respectively. We report here that imidazole derivative drugs: the anthelminthics, albendazole and thiabendazole; the proton pump inhibitor, omeprazole; the thromboxane synthase inhibitor, benzylimidazole; and the aromatase (CYP19) inhibitor vorozole (R76713, racemate; and R83842, (؉) enantiomer) increased hepatic microsomal EET formation in a chick embryo model. Albendazole increased EETs by transcriptional induction of CYP1A5 and the others by combined induction of CYP1A5 and CYP2H, the avian orthologs of mammalian CYP1A2 and CYP2B, respectively. All inducers increased formation of the four EET regioisomers, but TCDD and albendazole had preference for 5,6-EET and PB and omeprazole for 14,15-EET. Vorozole, benzylimidazole, and TCDD also suppressed 20-HETE formation. Vorozole was a remarkably effective and potent inducer of multiple hepatic P450s at a dose range which overlapped its inhibition of ovarian aromatase. Increased CYP1A activity in mouse Hepa 1-6 and human HepG2 cells by vorozole and other imidazole derivatives demonstrated applicability of the findings to mammalian cells. The findings suggest that changes in P450-dependent arachidonic acid metabolism may be a new source of side effects for drugs that induce CYP1A or CYP2. They demonstrate further that in vivo induction of multiple hepatic P450s produces additive increases in arachidonic acid epoxygenase activity and can occur concurrently with inhibition of ovarian aromatase activity.

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Section: Discussionmentioning

confidence: 97%

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confidence: 99%

Induction of Cyp1a and Cyp2-Mediated Arachidonic Acid Epoxygenation and Suppression of 20-Hydroxyeicosatetraenoic Acid by Imidazole Derivatives Including the Aromatase Inhibitor Vorozole

Diani-Moore¹,

Papachristou²,

Labitzke³

et al. 2006

Drug Metab Dispos

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“…Thus, OME increases the expression of CYP1A1 and CYP1A2 in human hepatocytes (11) and in the human alimentary tract (12). The anthelmintic drugs albendazole (13), and oxfendazole (14), as well as thiabendazole (15,16), induce the CYP1A subfamily in rat and rabbit. The benzimidazoles also induce the expression of human CYP3A4 (17).…”

mentioning

confidence: 99%

Signal Transduction-mediated Activation of the Aryl Hydrocarbon Receptor in Rat Hepatoma H4IIE Cells

Backlund

Johansson

Mkrtchian

et al. 1997

Journal of Biological Chemistry

107

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We have investigated mechanisms of omeprazole (OME)-mediated induction of CYP1A1 and CYP3A, using the rat hepatoma H4IIE cell line, in comparison with mechanisms exerted by traditional aryl hydrocarbon receptor (AhR) ligands such as benso(a)pyrene (B(a)P) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). OME did not bind specifically to AhR, and it could not activate the AhR complex in rat cytosol to a xenobioticresponsive element (XRE)-binding form in vitro. Genistein, a tyrosine kinase inhibitor, and daidzein, an inhibitor of casein kinase II, efficiently inhibited OMEmediated but not B(a)P-or TCDD-mediated induction of CYP1A1, as monitored at the transcriptional, mRNA, and protein levels as well as by analysis of activation of XRE-luciferase reporter constructs transfected into H4IIE cells. The protease inhibitor N ␣ -p-tosyl-L-lysine chloromethyl ketone (TLCK) and lavendustin A also had similar OME-specific effects. In addition, insulin pretreatment caused an almost complete inhibition of OMEdependent CYP1A1 induction but only partially affected TCDD and B(a)P-mediated induction of CYP1A1. Staurosporine, an inhibitor of protein kinase C, impaired the induction by both B(a)P and OME. OME caused an approximately 2-fold increase in the level of CYP3A expression, but all inhibitors used were ineffective in preventing this induction. Gel shift analysis with radiolabeled XRE and specific peptide antibodies toward AhR and aryl hydrocarbon receptor nuclear translocator protein (Arnt) revealed an OME-mediated translocation of the AhR⅐Arnt complex into the nuclei. Genistein inhibited the specific nuclear XRE binding caused by OME, but it potentiated the formation of the TCDD-induced XRE⅐AhR complex. Although daidzein was able to effectively inhibit the OME-stimulated CYP1A1 gene transcription, it did not influence the OMEdependent AhR⅐XRE complex formation. The data are consistent with a mechanism for OME-mediated induction of CYP1A1 that involves activation of the AhR complex via intracellular signal transduction systems and that is distinct from induction mediated by AhR ligands.

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“…benzimidazoles are capable to induce both isoforms (Daujat et al, 1992;Rey-Grobellet et al, 1996). Furthermore, herbimycin A, was also capable of partially reducing the 3-MC-dependent induction.…”

Section: Discussionmentioning

confidence: 94%

“…Indeed, in rat hepatocytes, Shih et al (1999) have shown that maximal level expression of CYP1A1 mRNA occurs after 9 h of treatment, then dramatically decreased after 24 h of treatment with 100 AM OME. Moreover, in rabbit hepatocytes, Rey-Grobellet et al (1996) showed that when transcription was inhibited by actinomycin D, CYP1A1 protein induction was reduced. Therefore, the 3 steps leading to CYP1A1 induction are: activation of gene transcription, mRNA stabilization and protein translation (Lewis, 2001).…”

Section: Discussionmentioning

confidence: 98%

The role of protein tyrosine kinases in CYP1A1 induction by omeprazole and thiabendazole in rat hepatocytes

Lemaire¹,

Delescluse²,

Pralavorio³

et al. 2004

Life Sciences

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Structural Requirements for the Induction of Cytochromes P450 by Benzimidazole Anthelmintic Derivatives in Cultured Rabbit Hepatocytes

Cited by 20 publications

References 0 publications

Induction of Cyp1a and Cyp2-Mediated Arachidonic Acid Epoxygenation and Suppression of 20-Hydroxyeicosatetraenoic Acid by Imidazole Derivatives Including the Aromatase Inhibitor Vorozole

Induction of Cyp1a and Cyp2-Mediated Arachidonic Acid Epoxygenation and Suppression of 20-Hydroxyeicosatetraenoic Acid by Imidazole Derivatives Including the Aromatase Inhibitor Vorozole

Signal Transduction-mediated Activation of the Aryl Hydrocarbon Receptor in Rat Hepatoma H4IIE Cells

The role of protein tyrosine kinases in CYP1A1 induction by omeprazole and thiabendazole in rat hepatocytes

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