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Modulation of aryl hydrocarbon receptor‐regulated genes by acute administration of ammonium metavanadate in kidney, lung and heart of C57BL/6 mice
Author(s) -
Abdelhamid Ghada,
Amara Issa E.A.,
AnwarMohamed Anwar,
ElKadi Ayman O.S.
Publication year - 2013
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2774
Subject(s) - cyp1b1 , aryl hydrocarbon receptor , kidney , in vivo , chemistry , messenger rna , cyp1a2 , gene expression , medicine , endocrinology , receptor , gene , cytochrome p450 , pharmacology , biology , biochemistry , enzyme , transcription factor , microbiology and biotechnology
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. Copyright © 2012 John Wiley & Sons, Ltd.