Protective Effect of Cinnamaldehyde on METH-induced Neurotoxicity in PC12 Cells via Inhibition of Apoptotic Response and Oxidative Stress

Document Type: Research article

Authors

1 Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.

2 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

3 Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Ahl Al Bayt, Karbala, Iraq.

4 Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

5 Department of Clinical Toxicology, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.

6 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

7 Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

8 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

Methamphetamine (METH) is a potent central nervous system (CNS) stimulant and frequently used illegal drugs. Repeated exposure to METH can induce degenerative changes in dopaminergic and serotonergic axons. There is no standard medical treatment for METH’s neurotoxic effects. Cinnamaldehyde is an important compound of cinnamon and has activities against neurological disorders. The present study was designed to examine the neuroprotective effect of trans-cinnamaldehyde (TCA) on METH-induced cytotoxicity. PC12 cells were treated with METH (2.5 mM) 24 h after treated with different concentrations of TCA (3.75- 50 μM). The percentage of cell survival was evaluated by MTT assay and the following parameters were measured to detect apoptosis and oxidative stress responses: DNA fragmentation, ROS production and GSH content. Exposure to 2.5 mM METH decreased the cell viability and GSH levels, caused the generation of reactive oxygen species and ultimately induced apoptosis. Pretreatment with TCA at 3.125-25 μM significantly attenuated cell viability loss. TCA, especially at a concentration of 12.5 and 25 μM, decreased the apoptosis and ROS generation and increased the GSH level compared with the METH group. The findings of the present study suggested that TCA exerted a protective effect against METH-induced neurotoxicity through mechanisms related to antioxidant and anti-apoptosis. It is suggested that TCA may be useful for the prevention and treatment of harmful effects of METH on the brain.

Graphical Abstract

Protective Effect of Cinnamaldehyde on METH-induced Neurotoxicity in PC12 Cells via Inhibition of Apoptotic Response and Oxidative Stress

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