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

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Abstract

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.

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Acknowledgments

This article has been extracted from the MSc thesis written by F. Aghajanpour and the present article is financially supported by School of Medicine, Shahid Beheshti University of Medical Sciences (Registration No: 16116).

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Authors and Affiliations

  1. Cell Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Fakhroddin Aghajanpour, Ali Jahanian, Reza Soltani, Samira Ezi, Aysan Khatmi, Mohammad-Amin Abdollahifar, Seyed Hamidreza Mirbehbahani, Hossein Toreyhi, Abbas Aliaghaei & Abdollah Amini

  2. Department of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland

    Mahdi Eskandarian Boroujeni

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  1. Fakhroddin Aghajanpour
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  2. Mahdi Eskandarian Boroujeni
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Correspondence to Abbas Aliaghaei or Abdollah Amini.

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The research was approved by the Animal Care and Use Committee of Shahid Beheshti University of Medical Sciences (IR SBMU.MSP.REC.1398.292).

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Aghajanpour, F., Boroujeni, M.E., Jahanian, A. et al. Tramadol: a Potential Neurotoxic Agent Affecting Prefrontal Cortices in Adult Male Rats and PC-12 Cell Line. Neurotox Res 38, 385–397 (2020). https://doi.org/10.1007/s12640-020-00214-z

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  • DOI: https://doi.org/10.1007/s12640-020-00214-z

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