Duloxetine attenuates paclitaxel-induced peripheral nerve injury by inhibiting p53-related pathways

Abstract

Paclitaxel (PTX) is an antineoplastic drug extracted from the Taxus species, and peripheral neuropathy is a common side effect. Paclitaxel-induced peripheral neuropathy (PIPN) seriously affects patient quality of life. Currently, the mechanism of PIPN is still unknown, and few treatments are recognized clinically. Duloxetine is recommended as the only potential treatment of chemotherapy-induced peripheral neuropathy (CIPN) by the American Society of Clinical Oncology. However, this guidance lacks a theoretical basis and experimental evidence. Our study suggested that duloxetine could improve PIPN and provide neuroprotection. We explored the potential mechanisms of duloxetine on PIPN. As a result, duloxetine acts by inhibiting poly ADP-ribose polymerase cleavage (PARP) and tumor suppressor gene p53 activation and regulating apoptosis regulator the Bcl2 family to reverse PTX-induced oxidative stress and apoptosis. Taken together, the present study shows that using duloxetine to attenuate PTX-induced peripheral nerve injury and peripheral pain may provide new clinical therapeutic targets for CIPN.