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Dapsone improves the vincristine-induced neuropathic nociception by modulating neuroinflammation and oxidative stress

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Abstract

Background

Peripheral neuropathy is a dose-limiting adverse effect of vincristine (VCR) in cancer chemotherapies. Dapsone is commonly used for the prevention of opportunistic infections following cancer therapies. Therefore, a high rate of VCR and dapsone co-administration has occurred in leukemias. Recently neuroprotective effects of dapsone have been reported in various diseases.

Objectives

Regarding the physiopathology of VCR-induced peripheral neuropathy (VIPN) and dapsone neuroprotection, this study evaluated the effect of dapsone on VIPN.

Methods

VIPN was induced by VCR injection (0.5 mg/kg IP, every other day, 1 week) in male Wistar rats. In the treatment group, dapsone(12.5 mg/kg IP, 1 week) was injected 30 min before VCR. Hot plate, Von Frey, motor neuron conduction velocity (MNCV), and histopathological tests were applied. The levels of TNF-α and NF-kB in the sciatic nerve and caspase-3 activity in dorsal root ganglion were measured by the ELISA method. The levels of malondialdehyde (MDA) and Glutathione (GSH) in the sciatic nerve were measured by spectrophotometry and colorimetric assays.

Results

VIPN was observed as araised thermal and mechanical threshold, reduced MNCV, and sciatic nerve demyelination. However, dapsone reduced the mechanical and thermal threshold and improved the MNCV. Also, dapsone reduced TNF-α, NF-kB, MDA, and Caspase-3 activity, and increased the GSH level in the sciatic nerve. Moreover, dapsone prevented VCR-induced demyelination in the sciatic nerve.

Conclusion

This research demonstrated that dapsone could be used as a protective drug against VIPN. It improves the impaired thermal and mechanical sensations by reducing inflammatory, oxidant, and apoptosis factors and preventing demyelination in the sciatic nerve.

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Data availability

All data details will be available upon request.

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Acknowledgements

We appreciate Gilaranco Co. for providing dapsone powder for this research. Special thanks go to the Mehr Laboratory for their help.

Funding

This study was supported by the National Institute for Medical Research Development [Grant No 971024] and Iran National Science Foundation (INSF).

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alborz University of Medical Sciences, Karaj, Iran

    Sevda Shayesteh

  2. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Sevda Shayesteh, Mina Khalilzadeh & Ahmad Reza Dehpour

  3. Department of Anatomy and Medicinal Plants Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Nasrin Takzaree

  4. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145‐784, Tehran, Iran

    Ahmad Reza Dehpour

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  1. Sevda Shayesteh
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Correspondence to Ahmad Reza Dehpour.

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Shayesteh, S., Khalilzadeh, M., Takzaree, N. et al. Dapsone improves the vincristine-induced neuropathic nociception by modulating neuroinflammation and oxidative stress. DARU J Pharm Sci 30, 303–310 (2022). https://doi.org/10.1007/s40199-022-00448-6

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  • DOI: https://doi.org/10.1007/s40199-022-00448-6

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