title: Modulation of aryl hydrocarbon receptor-regulated genes by acute administration of ammonium metavanadate in kidney, lung and heart of C57BL/6 mice.
abstract: We recently reported that vanadium (V(5+) ) was able to decrease the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated induction of Cyp1a1 and Nqo1 at mRNA, protein and catalytic activity levels in mouse hepatoma Hepa 1c1c7 and human hepatoma HepG2 cells. However, little is known regarding the in vivo effects. Thus, the objective of this study was to investigate whether similar effects would occur at the in vivo level. Therefore, we examined the effect of exposure to V(5+) (5 mg kg(-1) ) with or without TCDD (15 µg kg(-1) ) on the AhR-regulated genes in kidney, lung and heart of C57BL/6 J mice. Our results demonstrated that V(5+) alone significantly decreased Cyp1b1 protein and catalytic activity levels in kidney at 24 h. Moreover, it significantly potentiated Nqo1 and Gsta1 gene expression in the heart, and only Gsta1 gene expression in the lung. Upon co-exposure, we found that V(5+) significantly inhibited the TCDD-mediated induction of Cyp1a1, Cyp1a2 and Cyp1b1 mRNA, protein and catalytic activity levels in the kidney at 24 h. On the other hand, V(5+) significantly potentiated the TCDD-mediated induction of Nqo1 and Gsta1 protein and activity levels in the kidney. Cyp1a1, Cyp1b1, Nqo1 mRNA, protein and catalytic activity levels in the lung were significantly potentiated at 6 h. Interestingly, all tested genes in the heart were significantly decreased at 6 h with the exception of Gsta1 mRNA. The present study demonstrates that V(5+) modulates TCDD-induced AhR-regulated genes. Furthermore, the effect on one of these enzymes could not be generalized to other enzymes even if it was in the same organ.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada, T6G 2 N8.
authors.forename: Ghada
authors.initials: G
authors.lastname: Abdelhamid
authors.forename: Issa E A
authors.initials: IE
authors.lastname: Amara
authors.forename: Anwar
authors.initials: A
authors.lastname: Anwar-Mohamed
authors.forename: Ayman O S
authors.initials: AO
authors.lastname: El-Kadi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects*; D005982:Glutathione Transferase / Q000235:genetics; D006321:Heart / Q000187:drug effects*; D007527:Isoenzymes / Q000235:genetics; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D060888:Real-Time Polymerase Chain Reaction; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D014638:Vanadates / Q000494:pharmacology*
chemical_list: D007527:Isoenzymes; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D014638:Vanadates; C585498:Cyp1b1 protein, mouse; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D065633:Cytochrome P-450 CYP1B1; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha; C101036:ammonium metavanadate