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Tramadol induces apoptosis, inflammation, and oxidative stress in rat choroid plexus

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Abstract

Background

The choroid plexus (CP) is the principal source of cerebrospinal fluid (CSF). It can produce and release a wide range of materials, including growth and neurotrophic factors which have a crucial role in the maintenance and proper functioning of the brain. Tramadol is a synthetic analog of codeine, mainly prescribed to alleviate mild to moderate pains. Nevertheless, it causes several side effects, such as emotional instability and anxiety.

Methods

In this study, we focused on alterations in the expression of inflammatory and apoptotic genes in the CP under chronic tramadol exposure. Herein, rats were treated daily with tramadol at 50 mg/kg doses for three weeks. CSF samples were collected, with superoxide dismutase (SOD) and glutathione (GSH) measured in the CSF.

Results

We found that tramadol reduced the SOD and GSH levels in the CSF. Furthermore, the stereological analysis revealed a significant increase in the CP volume, epithelial cells, and capillary number upon tramadol administration. Tramadol elevated the number of blob mitochondria in CP. Also, we observed the upregulation of inflammatory and apoptosis genes following tramadol administration in the CP.

Conclusions

Our findings indicate that tramadol induces neurotoxicity in the CP via apoptosis, inflammation, and oxidative stress.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We are thankful for the funding provided by Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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Authors and Affiliations

  1. Department of Genetics, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran

    Maryam Mehranpour & Mitra Salehi

  2. Department of Anatomical Sciences, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran

    Meysam Hassani Moghaddam

  3. Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohammad-Amin Abdollahifar

  4. Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Abbas Aliaghaei

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  1. Maryam Mehranpour
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  2. Meysam Hassani Moghaddam
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  3. Mohammad-Amin Abdollahifar
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  4. Mitra Salehi
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  5. Abbas Aliaghaei
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Contributions

AA and MS designed and conceived the study, analyzed and interpreted the data, and revised the manuscript for intellectual contents; MHM and MAA wrote and revised the manuscript; MHM and MM performed the experiments; MS had a crucial role in data collection and revised the manuscript and drafted the manuscript for the intellectual content.

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Correspondence to Mitra Salehi or Abbas Aliaghaei.

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Ethical approval was obtained by the ethics committee of the Shahid Beheshti University of Medical Sciences, Tehran Iran (IR.SBMU.RETECH.REC.1400.751).

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Mehranpour, M., Moghaddam, M.H., Abdollahifar, MA. et al. Tramadol induces apoptosis, inflammation, and oxidative stress in rat choroid plexus. Metab Brain Dis 38, 2679–2690 (2023). https://doi.org/10.1007/s11011-023-01307-2

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