Toxicity of new synthetic amphetamine drug mephedrone On Rat Heart mitochondria: a warning for its abuse

Abstract

1. Mephedrone, a new and popular amphetamine drug, is widely abused and is still legal in some parts around the world. Little data on mechanisms involved in mephedrone induced cardiotoxicity are available.

2. Therefore, we decided to explain the mechanisms of mephedrone cardiotoxicity by using mitochondria isolated from rat heart. The isolated heart mitochondria were incubated with different concentrations of mephedrone (5, 10 and 20 µM).

3. Results showed that mephedrone induced mitochondrial dysfunction via an increase in mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) collapse, mitochondrial swelling and damage in the mitochondrial outer membrane (MOM) which is associated with the cytochrome c release. Our results showed that decrease of ATP levels is an indicator of disturbance in oxidative phosphorylation. Also, mephedrone increased the caspase-3 activity.

4. According to the results, we suggest that mephedrone induced cardiotoxicity is the result of a disruptive effect on the mitochondrial respiratory chain and induction of ROS-mediated apoptosis signaling in heart cardiomyocytes.

Keywords:

• Apoptosis
• heart mitochondria
• mephedrone
• ROS

Acknowledgements

The results presented in this paper were partly extracted from the thesis of Dr. Farzaneh vafaiee Pharm.D, the graduate of Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences who performed her thesis under the supervision of Professor Jalal Pourahmad. The investigation was carried out in Professor J. Pourahmad’s laboratory at the Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Declaration of interest

The authors declare no conflict of interest. The authors received no funding from any organization to perform this study.