Alleviation of cisplatin-induced neuropathic pain, neuronal apoptosis, and systemic inflammation in mice by rapamycin

Alotaibi, Moureq and Al-Aqil, Faten and Alqahtani, Faleh and Alanazi, Miteb and Nadeem, Ahmed and Ahmad, Sheikh F. and Lapresa, Rebeca and Alharbi, Metab and Alshammari, Abdulrahman and Alotaibi, Muteb and Saleh, Tareq and Alrowis, Raed (2022) Alleviation of cisplatin-induced neuropathic pain, neuronal apoptosis, and systemic inflammation in mice by rapamycin. Frontiers in Aging Neuroscience, 14. ISSN 1663-4365

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Abstract

Platinum-based chemotherapeutic treatment of cancer patients is associated with debilitating adverse effects. Several adverse effects have been well investigated, and can be managed satisfactorily, but chemotherapy-induced peripheral neuropathy (CIPN) remains poorly treated. Our primary aim in this study was to investigate the neuroprotective effect of the immunomodulatory drug rapamycin in the mitigation of cisplatin-induced neurotoxicity. Pain assays were performed in vivo to determine whether rapamycin would prevent or significantly decrease cisplatin-induced neurotoxicity in adult male Balb/c mice. Neuropathic pain induced by both chronic and acute exposure to cisplatin was measured by hot plate assay, cold plate assay, tail-flick test, and plantar test. Rapamycin co-treatment resulted in significant reduction in cisplatin-induced nociceptive-like symptoms. To understand the underlying mechanisms behind rapamycin-mediated neuroprotection, we investigated its effect on certain inflammatory mediators implicated in the propagation of chemotherapy-induced neurotoxicity. Interestingly, cisplatin was found to significantly increase peripheral IL-17A expression and CD8- T cells, which were remarkably reversed by the pre-treatment of mice with rapamycin. In addition, rapamycin reduced the cisplatin-induced neuronal apoptosis marked by decreased neuronal caspase-3 activity. The rapamycin neuroprotective effect was also associated with reversal of the changes in protein expression of p21Cip1, p53, and PUMA. Collectively, rapamycin alleviated some features of cisplatin-induced neurotoxicity in mice and can be further investigated for the treatment of cisplatin-induced peripheral neuropathy.

Item Type: Article
Subjects: Science Global Plos > Medical Science
Depositing User: Unnamed user with email support@science.globalplos.com
Date Deposited: 30 Sep 2023 12:52
Last Modified: 30 Sep 2023 12:52
URI: http://ebooks.manu2sent.com/id/eprint/1425

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