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Comparison of neuroprotective effects of a topiramate-loaded biocomposite based on mesoporous silica nanoparticles with pure topiramate against methylphenidate-induced neurodegeneration

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Abstract

Background

Methylphenidate (MPH) abuse has been criticized for its role in neurodegeneration. Also, a high risk of seizure was reported in the first month of MPH treatment. Topiramate, a broad-spectrum Antiepileptic Drug (AED), has been used as a neuroprotective agent in both aforementioned complications. Nanotechnology is introduced to increase desirable neurological treatment with minimum side effects. We aimed to investigate the potential neuroprotective activity of topiramate loaded on nanoparticles.

Methods and results

MTT assay was performed to evaluate the cellular cytotoxicity of Mesoporous Silica Nanoparticles (MSN). Male rats were randomly divided into eight groups. Rats received an intraperitoneal (i.p) MPH (10 mg/kg) injection and a daily oral dose of topiramate (TPM, 30 mg/kg), MSN with Zn core (10 and 30 mg/kg), and MSN with Cu core (10 and 30 mg/kg) for three weeks. On day 21, a seizure was induced by a single injection of pentylenetetrazole (PTZ) to evaluate the protective effects of TPM-loaded nanoparticles on seizure latency and duration following MPH-induced neurotoxicity. Moreover, the hippocampal content of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), and the anti-oxidant enzymes (SOD, GPx, and GR) activities were assessed. Also, BAX and Bcl-2 as two main apoptotic markers were evaluated.

Results

MPH neurotoxicity was observed as a raised duration and reduced latency in PTZ-induced seizure. However, TPM-loaded MSN with Zn species (NE) treatment reduced the duration and improved the latency time. Also, NE and, somewhat, TPM-loaded MSN with Cu species (NM) administration reduced inflammatory cytokines, MDA, and Bax levels and increased activities in the rat hippocampus.

Conclusion

TPM-loaded nanoparticles could be used as neuroprotective agents against MPH-induced neurodegeneration by improving seizure parameters and reducing inflammatory, oxidant, and apoptotic factors.

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Acknowledgements

The authors would like to thank Dr Khalili and Dr Amri for their assistance.

Funding

This work has received financial support from the research deputy of Iran University of Medical Sciences, Tehran, Iran (Grant No: 19568).

Author information

Author notes

  1. Erfan Pari and Mohammad Sheibani have contributed equally to this work.

Authors and Affiliations

  1. Faculty of Chemistry, North Tehran Branch, Islamic Azad University, Hakimiyeh, Tehran, Iran

    Erfan Pari, Mohammad Reza Sazegar & Saeedeh Mir

  2. Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Mohammad Sheibani, Ashrafsadat Moazam & Manijeh Motevalian

  3. Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran

    Mohammad Sheibani & Manijeh Motevalian

  4. Experimental Medicine Research Centre, Tehran University of Medical Sciences, Tehran, Iran

    Mina Khalilzadeh

  5. Pharmacology Department, Medical School & Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran

    Manijeh Motevalian

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by E.P., M.S., M.S. and M.M.: Experimental steps were performed by E.P., M.S., A.M., and S.M.: The first draft of the manuscript was written by M.K. and M.S. Critical revisions were made by M.S. and M.M. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Mohammad Reza Sazegar or Manijeh Motevalian.

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Ethical approval

The protocol of this study was approved by the Ethics Committee of Iran University of Medical Sciences (Ethics code: IR.IUMS.REC.1400.544).

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Pari, E., Sheibani, M., Sazegar, M.R. et al. Comparison of neuroprotective effects of a topiramate-loaded biocomposite based on mesoporous silica nanoparticles with pure topiramate against methylphenidate-induced neurodegeneration. Mol Biol Rep 51, 65 (2024). https://doi.org/10.1007/s11033-023-09011-1

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