Effect of 3,4-Methylenedioxymethamphetamine on Liver CYP2C19 Enzyme Activity in Isolated Perfused Rat Liver Using Omeprazole Probe
Background and purpose: This study aimed at investigating the effects of 3,4-Methylenedioxymethamphetamine (MDMA) on liver cytochrome 2C19 enzyme activity, which is a major liver enzyme in the metabolism of a wide range of drugs, using omeprazole as a probe of the CYP2C19 activity in isolated perf...
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| Format: | Article |
| Language: | English |
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Mazandaran University of Medical Sciences
2020-07-01
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| Series: | Journal of Mazandaran University of Medical Sciences |
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| Online Access: | http://jmums.mazums.ac.ir/article-1-14167-en.html |
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| author | Mohammadreza Rouini Navid Neyshaburinezhad Alireza Foroumadi Hoda Lavasani Yalda Hosseinzadeh Ardakani |
| author_facet | Mohammadreza Rouini Navid Neyshaburinezhad Alireza Foroumadi Hoda Lavasani Yalda Hosseinzadeh Ardakani |
| author_sort | Mohammadreza Rouini |
| collection | DOAJ |
| description | Background and purpose: This study aimed at investigating the effects of 3,4-Methylenedioxymethamphetamine (MDMA) on liver cytochrome 2C19 enzyme activity, which is a major liver enzyme in the metabolism of a wide range of drugs, using omeprazole as a probe of the CYP2C19 activity in isolated perfused rat liver.
Materials and methods: This experimental study was done in 20 male Sprague–Dawley (SD) rats (weighing 250–300 g). After isolating the animal liver, omeprazole was administered at 400 μm and the concentration of omeprazole and its metabolite were determined. The liver was then washed with perfusion buffer, and MDMA was transferred at 300 ng/ml unilaterally from the same liver for 30 minutes. After re-washing the liver with perfusion buffer, omeprazole was passed through the liver for second time and the metabolic ratio was determined after exposure to MDMA. This process was also done in a group of animals at 600 ng/ml of MDMA.
Results: Analysis of data from three end-time intervals after exposure to liver at 300 and 600 ng/ml of MDMA, showed 26.6% and 20.6% reduction in the activity of CYP2C19. Findings showed that MDMA administration could significantly reduce the activity of CYP2C19.
Conclusion: According to this study, liver exposure to MDMA can significantly reduce cytochrome 2C19 activity, but, further studies are needed to examine this issue more closely. |
| first_indexed | 2024-04-10T20:33:49Z |
| format | Article |
| id | doaj.art-54ae89c073e741699e24cc14d80d2150 |
| institution | Directory Open Access Journal |
| issn | 1735-9260 1735-9279 |
| language | English |
| last_indexed | 2024-04-10T20:33:49Z |
| publishDate | 2020-07-01 |
| publisher | Mazandaran University of Medical Sciences |
| record_format | Article |
| series | Journal of Mazandaran University of Medical Sciences |
| spelling | doaj.art-54ae89c073e741699e24cc14d80d21502023-01-25T05:00:42ZengMazandaran University of Medical SciencesJournal of Mazandaran University of Medical Sciences1735-92601735-92792020-07-0130187114Effect of 3,4-Methylenedioxymethamphetamine on Liver CYP2C19 Enzyme Activity in Isolated Perfused Rat Liver Using Omeprazole ProbeMohammadreza Rouini0Navid Neyshaburinezhad1Alireza Foroumadi2Hoda Lavasani3Yalda Hosseinzadeh Ardakani4 Professor, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Resident in Pharmaceutical Sciences, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Professor, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran MSc in Developmental Bioloigy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Associate Professor, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Background and purpose: This study aimed at investigating the effects of 3,4-Methylenedioxymethamphetamine (MDMA) on liver cytochrome 2C19 enzyme activity, which is a major liver enzyme in the metabolism of a wide range of drugs, using omeprazole as a probe of the CYP2C19 activity in isolated perfused rat liver. Materials and methods: This experimental study was done in 20 male Sprague–Dawley (SD) rats (weighing 250–300 g). After isolating the animal liver, omeprazole was administered at 400 μm and the concentration of omeprazole and its metabolite were determined. The liver was then washed with perfusion buffer, and MDMA was transferred at 300 ng/ml unilaterally from the same liver for 30 minutes. After re-washing the liver with perfusion buffer, omeprazole was passed through the liver for second time and the metabolic ratio was determined after exposure to MDMA. This process was also done in a group of animals at 600 ng/ml of MDMA. Results: Analysis of data from three end-time intervals after exposure to liver at 300 and 600 ng/ml of MDMA, showed 26.6% and 20.6% reduction in the activity of CYP2C19. Findings showed that MDMA administration could significantly reduce the activity of CYP2C19. Conclusion: According to this study, liver exposure to MDMA can significantly reduce cytochrome 2C19 activity, but, further studies are needed to examine this issue more closely.http://jmums.mazums.ac.ir/article-1-14167-en.htmlmetabolismmdmaomeprazoleliver perfusioncyp2c199 |
| spellingShingle | Mohammadreza Rouini Navid Neyshaburinezhad Alireza Foroumadi Hoda Lavasani Yalda Hosseinzadeh Ardakani Effect of 3,4-Methylenedioxymethamphetamine on Liver CYP2C19 Enzyme Activity in Isolated Perfused Rat Liver Using Omeprazole Probe Journal of Mazandaran University of Medical Sciences metabolism mdma omeprazole liver perfusion cyp2c199 |
| title | Effect of 3,4-Methylenedioxymethamphetamine on Liver CYP2C19 Enzyme Activity in Isolated Perfused Rat Liver Using Omeprazole Probe |
| title_full | Effect of 3,4-Methylenedioxymethamphetamine on Liver CYP2C19 Enzyme Activity in Isolated Perfused Rat Liver Using Omeprazole Probe |
| title_fullStr | Effect of 3,4-Methylenedioxymethamphetamine on Liver CYP2C19 Enzyme Activity in Isolated Perfused Rat Liver Using Omeprazole Probe |
| title_full_unstemmed | Effect of 3,4-Methylenedioxymethamphetamine on Liver CYP2C19 Enzyme Activity in Isolated Perfused Rat Liver Using Omeprazole Probe |
| title_short | Effect of 3,4-Methylenedioxymethamphetamine on Liver CYP2C19 Enzyme Activity in Isolated Perfused Rat Liver Using Omeprazole Probe |
| title_sort | effect of 3 4 methylenedioxymethamphetamine on liver cyp2c19 enzyme activity in isolated perfused rat liver using omeprazole probe |
| topic | metabolism mdma omeprazole liver perfusion cyp2c199 |
| url | http://jmums.mazums.ac.ir/article-1-14167-en.html |
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