Inhibition of CYP1A1 by pharmaceutical drugs, omeprazol and ketoconazole as a mechanism for activation of aryl hydrocarbon receptor (AHR)
Omeprazole (OMP) and ketoconazole (KTZ) have been shown to activate the 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 KTZ and OMP can act as indirect activator of AHR. In order to evaluate the effec...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Shiraz University of Medical Sciences
2017-03-01
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| Series: | Trends in Pharmaceutical Sciences |
| Subjects: | |
| Online Access: | https://tips.sums.ac.ir/article_42214_08ef8801fe87a9c65b3d8bd4b2127be6.pdf |
| _version_ | 1818883627324276736 |
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| author | Ali Ghaffarian-Bahraman Nilofar Sadeghimanesh Mona Mirzaei Amin-Reza Akbarizadeh Mahmoud Omidi Hamidreza Mohammadi Mohammad-Reza Arabnezhad Keivan Mobini Afshin Mohammadi-Bardbori |
| author_facet | Ali Ghaffarian-Bahraman Nilofar Sadeghimanesh Mona Mirzaei Amin-Reza Akbarizadeh Mahmoud Omidi Hamidreza Mohammadi Mohammad-Reza Arabnezhad Keivan Mobini Afshin Mohammadi-Bardbori |
| author_sort | Ali Ghaffarian-Bahraman |
| collection | DOAJ |
| description | Omeprazole (OMP) and ketoconazole (KTZ) have been shown to activate the 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 KTZ and OMP can act as indirect activator of AHR. In order to evaluate the effects of KTZ and OMP on AHR signaling, we measured cytochromes p450 (CYP1A1) enzyme activity by ethoxyresorufin-O-deethylase (EROD) assay as endpoint. FICZ, at 1nM concentration, caused a transient elevation in the catalytic activity of CYP 1A1. KTZ and OMP were found to be inducer of CYP1A1 at concentrations above 50 µM. At early time of incubation (3hr), a dose-dependent inhibition of FICZ-induced EROD activity was seen. When OMP or KTZ were added together with FICZ, a prolonged activation of CYP1A1 was observed at later time of incubation (24h). Taken together, our findings support the earlier observation that we shown that CYP 1A1 inhibitors can act as an AHR activator though inhibition of metabolic degradation of FICZ. |
| first_indexed | 2024-12-19T15:36:39Z |
| format | Article |
| id | doaj.art-7336ba9cbda542f3b8bc35605960aef6 |
| institution | Directory Open Access Journal |
| issn | 2423-5652 |
| language | English |
| last_indexed | 2024-12-19T15:36:39Z |
| publishDate | 2017-03-01 |
| publisher | Shiraz University of Medical Sciences |
| record_format | Article |
| series | Trends in Pharmaceutical Sciences |
| spelling | doaj.art-7336ba9cbda542f3b8bc35605960aef62022-12-21T20:15:35ZengShiraz University of Medical SciencesTrends in Pharmaceutical Sciences2423-56522017-03-0131131842214Inhibition of CYP1A1 by pharmaceutical drugs, omeprazol and ketoconazole as a mechanism for activation of aryl hydrocarbon receptor (AHR)Ali Ghaffarian-BahramanNilofar SadeghimaneshMona MirzaeiAmin-Reza AkbarizadehMahmoud OmidiHamidreza MohammadiMohammad-Reza ArabnezhadKeivan MobiniAfshin Mohammadi-BardboriOmeprazole (OMP) and ketoconazole (KTZ) have been shown to activate the 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 KTZ and OMP can act as indirect activator of AHR. In order to evaluate the effects of KTZ and OMP on AHR signaling, we measured cytochromes p450 (CYP1A1) enzyme activity by ethoxyresorufin-O-deethylase (EROD) assay as endpoint. FICZ, at 1nM concentration, caused a transient elevation in the catalytic activity of CYP 1A1. KTZ and OMP were found to be inducer of CYP1A1 at concentrations above 50 µM. At early time of incubation (3hr), a dose-dependent inhibition of FICZ-induced EROD activity was seen. When OMP or KTZ were added together with FICZ, a prolonged activation of CYP1A1 was observed at later time of incubation (24h). Taken together, our findings support the earlier observation that we shown that CYP 1A1 inhibitors can act as an AHR activator though inhibition of metabolic degradation of FICZ.https://tips.sums.ac.ir/article_42214_08ef8801fe87a9c65b3d8bd4b2127be6.pdfcyp1a1omeprazolketoconazolearyl hydrocarbon receptor (ahr)ficz |
| spellingShingle | Ali Ghaffarian-Bahraman Nilofar Sadeghimanesh Mona Mirzaei Amin-Reza Akbarizadeh Mahmoud Omidi Hamidreza Mohammadi Mohammad-Reza Arabnezhad Keivan Mobini Afshin Mohammadi-Bardbori Inhibition of CYP1A1 by pharmaceutical drugs, omeprazol and ketoconazole as a mechanism for activation of aryl hydrocarbon receptor (AHR) Trends in Pharmaceutical Sciences cyp1a1 omeprazol ketoconazole aryl hydrocarbon receptor (ahr) ficz |
| title | Inhibition of CYP1A1 by pharmaceutical drugs, omeprazol and ketoconazole as a mechanism for activation of aryl hydrocarbon receptor (AHR) |
| title_full | Inhibition of CYP1A1 by pharmaceutical drugs, omeprazol and ketoconazole as a mechanism for activation of aryl hydrocarbon receptor (AHR) |
| title_fullStr | Inhibition of CYP1A1 by pharmaceutical drugs, omeprazol and ketoconazole as a mechanism for activation of aryl hydrocarbon receptor (AHR) |
| title_full_unstemmed | Inhibition of CYP1A1 by pharmaceutical drugs, omeprazol and ketoconazole as a mechanism for activation of aryl hydrocarbon receptor (AHR) |
| title_short | Inhibition of CYP1A1 by pharmaceutical drugs, omeprazol and ketoconazole as a mechanism for activation of aryl hydrocarbon receptor (AHR) |
| title_sort | inhibition of cyp1a1 by pharmaceutical drugs omeprazol and ketoconazole as a mechanism for activation of aryl hydrocarbon receptor ahr |
| topic | cyp1a1 omeprazol ketoconazole aryl hydrocarbon receptor (ahr) ficz |
| url | https://tips.sums.ac.ir/article_42214_08ef8801fe87a9c65b3d8bd4b2127be6.pdf |
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