Valproate Protective Effects on Cisplatin-induced Peripheral Neuropathy: An In Vitro and In Vivo Study

Abstract

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.