A comparison of mitochondrial toxicity of mephedrone on three separate parts of brain including hippocampus, cortex and cerebellum

Abstract

Mephedrone (4-methylmethcathinone) is a new and popular drug of abuse and also widely available on the internet and still legal in some parts of the world. The central nervous system is the target of mephedrone and recent evidence suggested that mephedrone could affect mitochondria in brain tissue. However, the underlying mechanisms of mephedrone toxicity in brain mitochondria have not yet been well understood. In this study, mitochondria from three separate parts of rat brain hippocampus, cortex, and cerebellum were obtained using differential centrifugation and were incubated with different concentrations of mephedrone (3, 6 and 12 μM). Then, the mitochondrial parameters toxicity were determined. The results showed that mephedrone (3, 6 and 12 μM) induced impairment in the activity of the mitochondrial complex II and IV. Also, mephedrone (3, 6 and 12 μM) increased mitochondrial reactive oxygen species (ROS) level, collapsed mitochondria membrane potential (MMP), induced swelling in the mitochondria and damaged the mitochondrial outer membrane (MOM) in the mitochondria obtained from hippocampus, cortex, and cerebellum, which in all cases is associated with the cytochrome c release. Furthermore, increased disturbance in oxidative phosphorylation was also shown by the decrease in ATP level in mephedrone-treated mitochondria indicating mitochondrial dysfunction in separate parts of the brain. This study suggests that mephedrone via increasing oxidative stress and impairment of the mitochondrial respiratory chain in the hippocampus, cortex, and cerebellum may play a key role in the neurotoxicity.