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Valproate protective effects on cisplatin-induced peripheral neuropathy: an in vitro and in vivo study
Virginia Rodriguez-Menendez1, Alessandra Gilardini, Mario Bossi
1Department of Neurosciences and Biomedical Technologies, University of Milano-Bicocca, Monza, Italy.
Background:
Antineoplastic drugs, such as cisplatin (CDDP), induce disabling peripheral neuropathies, representing a hindrance to effective cancer treatments. The exact pathogenesis of CDDP-induced neuropathy is not yet understood, and the dysregulation of gene expression has been proposed. Valproate (VPA) is an antiepileptic drug recently discovered to remodel gene expression, with hypothetically putative neuroprotective effects.
Materials And Methods:
VPA was tested in both, in vitro and in vivo models of CDDP-neurotoxicity.
Results:
VPA administered in combination with CDDP promoted dorsal root ganglia (DRG) neurons survival. Moreover, this treatment induced in Wistar rats an improvement of body weight, sensory nerve conduction velocity, and DRG morphometric analysis. In contrast, VPA was not able to rescue CDDP pre-treated rats.
Conclusion:
When used in combination with CDDP, VPA displays a protective action against neuropathy, in our models, suggesting possible future clinical applications.
Insights
Valproate (VPA) protects against cisplatin (CDDP)-induced neuropathy by preserving nerve cells and function in preclinical models. This suggests VPA may be a future therapeutic option for chemotherapy-induced nerve damage.
Area of Science:
- Neuroscience
- Pharmacology
- Oncology
Background:
- Cisplatin (CDDP) chemotherapy causes debilitating peripheral neuropathies, limiting treatment efficacy.
- The precise mechanisms of CDDP-induced neuropathy are unclear, but gene expression dysregulation is implicated.
- Valproate (VPA), an antiepileptic, modulates gene expression and may offer neuroprotection.
Purpose of the Study:
- To investigate the potential neuroprotective effects of valproate (VPA) against cisplatin (CDDP)-induced peripheral neuropathy.
- To evaluate VPA's efficacy in both in vitro and in vivo models of CDDP neurotoxicity.
Main Methods:
- In vitro and in vivo experimental models were utilized to assess CDDP-induced neurotoxicity.
- VPA was administered concurrently with CDDP in preclinical models.
- Neuroprotective effects were evaluated through neuronal survival assays, body weight monitoring, nerve conduction velocity measurements, and dorsal root ganglia (DRG) morphometric analysis.
Main Results:
- Concurrent administration of VPA with CDDP enhanced the survival of dorsal root ganglia (DRG) neurons in vitro.
- In Wistar rats, the combination treatment improved body weight, sensory nerve conduction velocity, and DRG morphology.
- VPA did not demonstrate a rescue effect in rats that were pre-treated with CDDP.
Conclusions:
- Valproate (VPA) exhibits a protective effect against cisplatin (CDDP)-induced neuropathy when administered concurrently in preclinical models.
- These findings suggest potential clinical applications for VPA in mitigating chemotherapy-induced peripheral neuropathy.
