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Updated: Feb 2, 2026

Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity
Published on: April 26, 2012
Fisetin protects against rotenone-induced neurotoxicity through signaling pathway
Malathi Rajendran1, Rajamurugan Ramachandran1
1Department of Biochemistry, Research and Development Centre, Bharathiar University, Coimbatore- 641046, Tamil Nadu, India.
Abstract:
The present study was designed to evaluate the protective effect of fisetin against rotenone induced toxicity in SH-SY5Y neuroblastoma cellular model of Parkinson's disease (PD). SH-SY5Y neuroblastoma cells were treated with fisetin (5µM) 2 hr prior to being treated with rotenone (100 nM). Following the exposure of SH-SY5Y cells to rotenone, there was marked decreased cell viability, increased oxidative stress, activation of caspase-3 and apoptosis (dual staining, expressions of pro-apoptotic and anti-apoptotic indices). However pretreatment with fisetin significantly and dose-dependently alleviated rotenone induced cytotoxicity and oxidative stress in SH-SY5Y cells. Moreover, fisetin attenuated rotenone induced toxicity by down-regulating Bax, caspases-3 protein expression and up-regulating protein expression of Bcl-2, p38/JNK-MAPK and PI3K, Akt, GSK-3β pathways. Collectively, these results suggest that fisetin could prevent the rotenone-induced neurotoxicity via various signaling pathways.
Insights
Fisetin protects against rotenone-induced neurotoxicity in Parkinson
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Parkinson's disease (PD) is a neurodegenerative disorder.
- Rotenone exposure models PD-like neurotoxicity.
- SH-SY5Y neuroblastoma cells are a common cellular model for PD research.
Purpose of the Study:
- To evaluate the protective effect of fisetin against rotenone-induced toxicity.
- To investigate the molecular mechanisms underlying fisetin's neuroprotection.
Main Methods:
- SH-SY5Y cells were pretreated with fisetin before rotenone exposure.
- Cell viability, oxidative stress, and apoptosis markers (caspase-3, Bax, Bcl-2) were assessed.
- Key signaling pathways (p38/JNK-MAPK, PI3K/Akt/GSK-3β) were analyzed.
Main Results:
- Rotenone significantly decreased cell viability, increased oxidative stress, and induced apoptosis.
- Fisetin pretreatment dose-dependently alleviated rotenone-induced cytotoxicity and oxidative stress.
- Fisetin modulated apoptosis-related proteins (Bax, Bcl-2) and key signaling pathways.
Conclusions:
- Fisetin exhibits significant neuroprotective effects against rotenone-induced toxicity in SH-SY5Y cells.
- Fisetin's protective mechanisms involve the modulation of apoptosis and multiple signaling pathways.
- Fisetin shows potential as a therapeutic agent for Parkinson's disease.
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