Effect of 3,4-Methylenedioxymethamphetamine on Liver CYP2C19 Enzyme Activity in Isolated Perfused Rat Liver Using Omeprazole Probe

Abstract

Background and purpose: This study aimed at investigating the effects of 3,4-Methyl​enedioxy​methamphetamine (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.

Keywords

• metabolism
• mdma
• omeprazole
• liver perfusion
• cyp2c199