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Modulation of aryl hydrocarbon receptor regulated genes by acute administration of trimethylarsine oxide in the lung, kidney and heart of C57BL/6 mice.
- Source :
-
Xenobiotica; the fate of foreign compounds in biological systems [Xenobiotica] 2015; Vol. 45 (10), pp. 930-43. Date of Electronic Publication: 2015 Jun 04. - Publication Year :
- 2015
-
Abstract
- 1. Arsenite alters the expression of aryl hydrocarbon receptor (AhR)-regulated genes in extrahepatic tissues; yet, the effect of organic arsenicals still unknown. Therefore, C57BL/6 mice received trimethylarsine oxide (TMAO; 13 mg/kg i.p.) with or without 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 15 μg/kg), and euthanized at 6 or 24 h. 2. Our results demonstrated that TMAO increased Cyp1a1 and Cyp1b1 mRNA, protein and activity in the lung. TMAO potentiated the TCDD-mediated induction of Cyp1a1 and Cyp1a2 mRNA, protein and activity in the lung. In the kidney, TMAO increased Cyp1b1 mRNA and protein. TMAO potentiated the TCDD-mediated induction of Cyp1a1 and Cyp1b1 mRNA, protein and activity. In the heart, TMAO potentiated the TCDD-mediated induction of Cyp1a1 and Cyp1b1 mRNA. 3. Moreover, TMAO induced Nqo1 mRNA in the lung, kidney and heart, with subsequent increase in Nqo1 protein and activity in the lung. TMAO increased Gsta mRNA in the heart; and increased Gsta protein and activity in the lung and kidney. TMAO increased Nqo1 mRNA as compared to TCDD in the kidney and heart, and potentiated the TCDD-mediated induction of Gsta protein and activity in the kidney. 4. In conclusion, TMAO modulates AhR-regulated genes in a tissue- and enzyme-specific manner.
- Subjects :
- Animals
Arsenicals pharmacology
Cytochrome P-450 CYP1A1 genetics
Cytochrome P-450 CYP1A1 metabolism
Cytochrome P-450 CYP1A2 genetics
Cytochrome P-450 CYP1A2 metabolism
Cytochrome P-450 CYP1B1 genetics
Cytochrome P-450 CYP1B1 metabolism
Enzymes metabolism
Glutathione Transferase genetics
Glutathione Transferase metabolism
Heart drug effects
Heme Oxygenase-1 genetics
Heme Oxygenase-1 metabolism
Isoenzymes genetics
Isoenzymes metabolism
Kidney drug effects
Lung drug effects
Male
Membrane Proteins genetics
Membrane Proteins metabolism
Mice, Inbred C57BL
NAD(P)H Dehydrogenase (Quinone) genetics
NAD(P)H Dehydrogenase (Quinone) metabolism
Polychlorinated Dibenzodioxins toxicity
Receptors, Aryl Hydrocarbon
Arsenicals pharmacokinetics
Enzymes genetics
Gene Expression Regulation drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1366-5928
- Volume :
- 45
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Xenobiotica; the fate of foreign compounds in biological systems
- Publication Type :
- Academic Journal
- Accession number :
- 26042454
- Full Text :
- https://doi.org/10.3109/00498254.2015.1032385