Author/Authors :
Ghafarian-bahraman، Ali نويسنده Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran , , Sadeghimanesh، Nilofar نويسنده Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran , , Mirzaei، Mona نويسنده Deapartment of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. , , Akbarizadeh، Amin Reza نويسنده Pharmaceutical Sciences Research Center, Shiraz University
of Medical Sciences, Shiraz, Iran , , Omidi، Mahmoud نويسنده Department of Toxicology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. , , Mohammadi، Hamidreza نويسنده Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran , , Arabnezhad، Mohammad-Reza نويسنده Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran , , Mobini، Keivan نويسنده Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran , , Mohammadi bardbori، Afshin نويسنده Department of Pharmacology Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran ,
Abstract :
Omeprazole and ketoconazole have been shown to activate the aryl hydrocarbon receptor (AHR) signaling pathway, in spite of the fact that they bind to the receptor with low or no affinity. The aim of this study was to investigate whether ketoconazole and omeprazole can act as indirect activators of AHR. In order to evaluate the effects of ketoconazole and omeprazole on AHR signaling, we measured cytochromes p450 (CYP1A1) enzyme activity by ethoxyresorufin-O-deethylase (EROD) assay as the endpoint. 6-formylindolo [3, 2-b]carbazole (FICZ), at 1nM concentration, caused a transient elevation in the catalytic activity of CYP 1A1. Ketoconazole and omeprazole were found to induce CYP1A1 at concentrations above 50 µM. At an early time of incubation (3hr), a dose-dependent inhibition of FICZ-induced EROD activity was seen. When omeprazole or ketoconazole were added together with FICZ, a prolonged activation of CYP1A1 was observed at a later time of incubation (24h). Taken together, our findings support our earlier observation that CYP 1A1 inhibitors can act as AHR activators though inhibition of metabolic degradation of FICZ.
