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Neuroprotective effects of gallic acid against docetaxel-induced peripheral neuropathy: behavioral, molecular, and
Özge Kandemir1, Hasan Şimşek2, Tuğba Çelik Samancı3
1Department of Food Processing, Aksaray Technical Sciences Vocational School, Aksaray University, Aksaray, Türkiye. ozgekandemir@aksaray.edu.tr.
Abstract:
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.
Insights
Gallic acid (GA) shows neuroprotective effects against docetaxel (DOC)-induced peripheral neuropathy by reducing oxidative stress and inflammation. This study suggests GA may be a potential supportive therapy for chemotherapy-induced nerve damage.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Docetaxel (DOC) is an effective chemotherapy agent, but its clinical use is limited by peripheral neuropathy.
- Oxidative stress is a key mechanism underlying DOC-induced neurotoxicity.
- Gallic acid (GA) is a natural polyphenol with known antioxidant properties.
Purpose of the Study:
- To investigate the potential neuroprotective effects of gallic acid (GA) against docetaxel (DOC)-induced peripheral neuropathy in a rat model.
- To evaluate the underlying molecular mechanisms, including oxidative stress, inflammation, apoptosis, autophagy, and endoplasmic reticulum stress.
Main Methods:
- Wistar rats were assigned to four groups: Control, GA, DOC, and DOC+GA.
- Neuroprotection was assessed using behavioral tests, oxidative stress markers (MDA, GSH, SOD, CAT, GPx), RT-PCR, and histopathological analyses.
- Immunohistochemical analysis was performed for GFAP and BDNF expression.
Main Results:
- DOC administration significantly impaired motor function and induced oxidative stress, inflammation, apoptosis, autophagy, and ER stress.
- Concurrent GA treatment significantly improved behavioral impairments and reversed oxidative stress markers.
- GA suppressed DOC-induced inflammation, apoptosis, autophagy, and ER stress, and partially repaired sciatic nerve damage, indicated by reduced GFAP and increased BDNF.
Conclusions:
- Gallic acid demonstrates significant neuroprotective effects against docetaxel-induced peripheral neuropathy.
- GA acts through multiple pathways, including antioxidant, anti-inflammatory, anti-apoptotic, and anti-autophagy mechanisms.
- GA shows potential as a supportive therapeutic agent to mitigate chemotherapy-induced nerve damage.
