Neuroprotective effects of gallic acid against docetaxel-induced peripheral neuropathy: behavioral, molecular, and histopathological evidence.

This study focuses on the potential neuroprotective effects of gallic acid (GA) against docetaxel (DOC)-induced peripheral neuropathy, which arises particularly through oxidative stress and limits the clinical use of this effective anti-mitotic chemotherapy agent. Twenty-eight Wistar rats were randomly assigned to four groups (n = 7): Control (saline), Gallic acid (GA, 200 mg/kg/day, oral), Docetaxel (DOC, 30 mg/kg, single dose i.p.), and Docetaxel + Gallic acid (DOC + GA). Peripheral neuropathy due to DOC and the potential protective effects of GA were evaluated using behavioral tests, oxidative stress and antioxidant parameters, RT-PCR, histopathological and GFAP/BDNF immunohistochemical analyses. DOC administration significantly impaired motor functions. GA treatment administered concurrently with DOC significantly improved these behavioral impairments (p < 0.001). Additionally, DOC increased MDA levels and decreased antioxidant defenses (GSH, SOD, CAT, GPx), whereas GA reversed these changes. GA also significantly suppressed DOC-induced inflammation (NF-κB, TNF-α, nNOS; p < 0.001), apoptosis (caspase-3, Bax, Bcl-2; p < 0.001), autophagy (Beclin-1, LC3A; p < 0.001), and endoplasmic reticulum stress (PERK, ATF6; p < 0.001). Morphological and immunohistochemical analyses demonstrated that GA partially repaired DOC-induced sciatic nerve damage, characterized by decreased GFAP immunoreactivity and improved BDNF expression. This study provides a comprehensive evaluation of the multitarget effects of GA on oxidative stress-related and stress-associated molecular pathways in a DOC-induced peripheral neuropathy model, offering preliminary insight into its potential as a supportive therapeutic approach.