Naringin is Protective in Paclitaxel-Induced Peripheral Neuropathy; A multi-biomarker approach

Abstract

Aim: Cancer is a disease that is on the rise worldwide. Paclitaxel (PTX) is one of the most common chemotherapeutic agents used in the treatment of many cancers. PTX causes toxic effects by increasing oxidative stress in tissues. Naringin is a powerful antioxidant found naturally in many plants, especially citrus fruits. The aim of this study was to determine the protective effects of NRG in PTX-induced sciatic nerve injury. Methods: Thirty-five male rats were randomly divided into five groups: control, PTX, NRG, PTX+NRG-50, PTX+NRG-100. PTX was administered i.p. for the first five days and NRG 50 or 100 mg/kg orally on days 6-14. Sciatic nerve tissues were harvested and analyzed for markers of oxidative stress, inflammation and apoptosis damage levels by biochemical methods. Results: PTX caused oxidative stress damage by increasing lipid peroxidation (MDA) and decreasing antioxidant capacity (SOD, CAT, GPx and GSH), inflammatory damage by increasing proinflammatory cytokine (NF-κB, TNF-α, IL-1β, SIRT1, TLR4, and NRF2) release, apoptotic damage by increasing apoptotic factor (Bax) and decreasing antiapoptotic factor (Bcl-2) in sciatic nerve tissue (p < 0.05). NRG, on the other hand, reversed all these changes in sciatic nerve tissue and reduced PTX-induced oxidative stress damage, inflammatory damage and apoptotic damage (p < 0.05). These effects were more effective at the 100 mg/kg dose of NRG than at the 50 mg/kg dose (p < 0.05). Conclusions: In sciatic nerve tissue, PTX induced peripheral neuropathy with increased oxidative stress, inflammation and apoptotic damage. NRG showed a protective effect against PTX-induced peripheral neuropathy.