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Gallic Acid Protects 6-OHDA Induced Neurotoxicity by Attenuating Oxidative Stress in Human Dopaminergic Cell Line

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Abstract

Gallic acid is one of the most important polyphenolic compounds, which is considered an excellent free radical scavenger. 6-Hydroxydopamine (6-OHDA) is a neurotoxin, which has been implicated in mainly Parkinson’s disease (PD). In this study, we investigated the molecular mechanism of the neuroprotective effects of gallic acid on 6-OHDA induced apoptosis in human dopaminergic cells, SH-SY5Y. Our results showed that 6-OHDA induced cytotoxicity in SH-SY5Y cells was suppressed by pre-treatment with gallic acid. The percentage of live cells (90%) was high in the pre-treatment of gallic acid when compared with 6-OHDA alone treated cell line. Moreover, gallic acid was very effective in attenuating the disruption of mitochondrial membrane potential, elevated levels of intracellular ROS and apoptotic cell death induced by 6-OHDA. Gallic acid also lowered the ratio of the pro-apoptotic Bax protein and the anti-apoptotic Bcl-2 protein in SH-SY5Y cells. 6-OHDA exposure was up-regulated caspase-3 and Keap-1 and, down-regulated Nrf2, BDNF and p-CREB, which were sufficiently reverted by gallic acid pre-treatment. These findings indicate that gallic acid is able to protect the neuronal cells against 6-OHDA induced injury and proved that gallic acid might potentially serve as an agent for prevention of several human neurodegenerative diseases caused by oxidative stress and apoptosis.

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Abbreviations

6-OHDA:

6-Hydroxydopamine

PD:

Parkinson’s disease

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

CAT:

Catalase

GPx:

Glutathione peroxidase

LDH:

Lactate dehydrogenase

GA:

Gallic acid

DCDFA:

2′,7′-Dichlorofluorescein diacetate

DMEM:

Dulbecco’s modified Eagle’s medium

ΔΨm:

Mitochondrial membrane potential

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Acknowledgements

We would like to thank Director, DFRL (DRDO) for his valuable suggestions.

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Authors and Affiliations

  1. Defence Food Research Laboratory, Nutritional Biochemistry and Toxicology Division, Siddhartha Nagar, Mysore, 570011, India

    Y. Chandrasekhar, G. Phani Kumar, E. M. Ramya & K. R. Anilakumar

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  1. Y. Chandrasekhar
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  2. G. Phani Kumar
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  3. E. M. Ramya
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  4. K. R. Anilakumar
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Correspondence to G. Phani Kumar.

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Chandrasekhar, Y., Phani Kumar, G., Ramya, E.M. et al. Gallic Acid Protects 6-OHDA Induced Neurotoxicity by Attenuating Oxidative Stress in Human Dopaminergic Cell Line. Neurochem Res 43, 1150–1160 (2018). https://doi.org/10.1007/s11064-018-2530-y

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