Tramadol: a Potential Neurotoxic Agent Affecting Prefrontal Cortices in Adult Male Rats and PC-12 Cell Line

Neurotoxicity Research - Tập 38 - Trang 385-397 - 2020
Fakhroddin Aghajanpour1, Mahdi Eskandarian Boroujeni2, Ali Jahanian1, Reza Soltani1, Samira Ezi1, Aysan Khatmi1, Mohammad-Amin Abdollahifar1, Seyed Hamidreza Mirbehbahani1, Hossein Toreyhi1, Abbas Aliaghaei1, Abdollah Amini1
1Cell Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2Department of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland

Tóm tắt

Tramadol is a synthetic analogue of codeine that is often prescribed for the treatment of mild to moderate pains. It has a number of side effects including emotional instability and anxiety. In this study, we focus on the structural and functional changes of prefrontal cortex under chronic exposure to tramadol. At the cellular level, the amounts of ROS and annexin V in PC12 cells were evidently increased upon exposure to tramadol (at a concentration of 600 μM for 48 h). To this end, the rats were daily treated with tramadol at doses of 50 mg/kg for 3 weeks. Our findings reveal that tramadol provokes atrophy and apoptosis by the induction of apoptotic markers such as Caspase 3 and 8, pro-inflammatory markers, and downregulation of GDNF. Moreover, it triggers microgliosis and astrogliosis along with neuronal death in the prefrontal cortex. Behavioral disturbance and cognitive impairment are other side effects of tramadol. Overall, our results indicate tramadol-induced neurodegeneration in the prefrontal cortex mainly through activation of neuroinflammatory response.

Tài liệu tham khảo

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