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Protective Effect of (−)Epigallocatechin-3-gallate on Rotenone-Induced Parkinsonism-like Symptoms in Rats

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Abstract

Rotenone (ROT)-induced neurotoxicity has been used for decades as an animal model of Parkinson’s disease (PD) in humans. This model exhibits pathophysiological features similar to those reported in patients with PD, namely, striatal nitrosative and oxidative stress, mitochondrial dysfunction, and neural cytoarchitecture alteration. (−)Epigallocatechin-3-gallate (EGCG), the most abundant and potent green tea catechin, has notable anti-oxidative, anti-inflammatory, and neuroprotective effects. The objective of the present study was to investigate the potential protective effects of EGCG on ROT-induced motor and neurochemical dysfunctions in rats. Furthermore, we also aimed to study the neuroprotective mechanisms underlying these effects. ROT treatment (0.5 mg/kg s.c., 21 days) reduced body weight and induced significant motor impairments as assessed using an open-field test, rotarod test, grip strength measurement, and beam-crossing task. EGCG treatment (100 or 300 mg/kg i.p., 60 min prior to ROT administration, 21 days) prevented most of the ROT-induced motor impairments. Moreover, EGCG treatment reduced ROT-induced nitric oxide (NO) level and lipid peroxidation (LPO) production; increased the activity of succinate dehydrogenase (SDH), ATPase, and ETC enzymes and the levels of catecholamines in the striatum; and reduced the levels of neuroinflammatory and apoptotic markers. These results demonstrate the possible neuroprotective effects of EGCG against ROT-induced motor impairments, including anti-oxidatory effect, prevention of mitochondrial dysfunction, prevention of neurochemical deficiency, anti-neuroinflammatory effect, and anti-apoptotic effect. This is the first report about the neuroprotective effect of EGCG against ROT-induced motor impairments, and the above evidence provides a potential clinically relevant role for EGCG in delaying or treating human PD.

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Acknowledgment

The authors thank Persistent BioMed Editing services located in Philadelphia, U.S.A. for their valuable editing and proof-reading of the current manuscript.

Funding

This study was supported by the Mackay Memorial Hospital (MMH-107-89) and Shin Kong Wu Ho-Su Memorial Hospital (SKH-8302-106-DR-23).

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Correspondence to Cheng-Chia Tsai.

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Tseng, HC., Wang, MH., Chang, KC. et al. Protective Effect of (−)Epigallocatechin-3-gallate on Rotenone-Induced Parkinsonism-like Symptoms in Rats. Neurotox Res 37, 669–682 (2020). https://doi.org/10.1007/s12640-019-00143-6

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