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Epigallocatechin Gallate Mitigates the Methamphetamine-Induced Striatal Dopamine Terminal Toxicity by Preventing Oxidative Stress in the Mouse Brain

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Abstract

Methamphetamine (METH) is a popular psychostimulant due to its long-lasting effects and inexpensive production. METH intoxication is known to increase oxidative stress leading to neuronal damage. Thus, preventing the METH-induced oxidative stress can potentially mitigate neuronal damage. Previously, our laboratory found that epigallocatechin gallate (EGCG), a strong antioxidant found in green tea, can protect against the METH-induced apoptosis and dopamine terminal toxicity in the striatum of mice. In the present study, we evaluated the anti-oxidative properties of EGCG on the METH-induced oxidative stress using CD-1 mice. First, we demonstrated that mice pretreated with EGCG 30 min prior to the METH injection (30 mg/kg, ip) showed protection against the striatal METH-induced reduction of tyrosine hydroxylase without mitigating hyperthermia. In addition, injecting a single high dose of METH caused the reduction of striatal glutathione peroxidase activity at 24 h after the METH injection. Interestingly, pretreatment with EGCG 30 min prior to the METH injection prevented the METH-induced reduction of glutathione peroxidase activity. Moreover, we utilized Western blots to quantify the glutathione peroxidase 4 protein level in the striatum. The results showed that METH decreased striatal glutathione peroxidase 4 protein level, and the reduction was prevented by EGCG pretreatment. Finally, we observed that the METH-induced increase of striatal catalase and copper/zinc superoxide dismutase protein levels were also attenuated by pretreatment with EGCG. Taken together, our data indicate that EGCG is an effective agent that can be used to mitigate the METH-induced striatal toxicity in the mouse brain.

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Abbreviations

CAT:

Catalase

EGCG:

Epigallocatechin gallate

GPx:

Glutathione peroxidase

ip:

Intraperitoneal

METH:

Methamphetamine

RIPA:

Radioimmunoprecipitation assay

ROS:

Reactive oxygen species

SOD-1:

Copper/zinc superoxide dismutase

TH:

Tyrosine hydroxylase

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Funding

This work was supported by R01 DA020142 from the National Institute on Drug Abuse to JAA. Support for infrastructure came from the National Institute on Minority Health and Health Disparities grant number 8 G12 MD007599 awarded to Hunter College by NIH.

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Correspondence to Jesus A. Angulo.

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Pan, A.L., Hasalliu, E., Hasalliu, M. et al. Epigallocatechin Gallate Mitigates the Methamphetamine-Induced Striatal Dopamine Terminal Toxicity by Preventing Oxidative Stress in the Mouse Brain. Neurotox Res 37, 883–892 (2020). https://doi.org/10.1007/s12640-020-00177-1

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