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Betanin Attenuates Oxidative Stress Induced by 6-OHDA in PC12 Cells via SAPK/JNK and PI3 K Pathways

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Abstract

Parkinson's disease is a neurodegenerative disorder which accompanied with cognitive decline, chorei form moves and behavioral difficulties. Oxidative stress which promote the apoptotic cell death are responsible for neurodegeneration in Parkinson. The purpose of this study is to evaluate the protective effects of betanin against toxicity and oxidative damage induced by 6-hydroxydopamine (6-OHDA) and hydrogen peroxide (H2O2) in PC12 cells as an appropriate model of Parkinson's cell damage. PC12 cells pretreated with betanin (1–200 µM) for 24 h, and exposed to either 6-OHDA (100 µM) or H2O2 (150 µM) for 24 h. Cell survival and intracellular reactive oxygen species (ROS) production analyzed by resazurin and DCF-DA assay. The anti-apoptotic effects of betanin in PC12 cells were studied using flow cytometry of PI stained cells. Also, western blot analysis of survivin, Cyt c, Phospho SAPK/JNK, SAPK/JNK, Phospho-PI3 kinase P85, PI3 kinase P85 was performed for detection of apoptosis. Betanin (1–200 µM) significantly decreased the 6-OHDA and H2O2 cytotoxicity also attenuated the ROS level. Cell apoptosis significantly increased after 6-OHDA (100 µM) treatment, compared to the control. However, pretreatment with betanin (20 and 50 µM), protected against apoptosis. Western blot analysis of PC12 cells showed that 100 µM 6-OHDA could increase the proteins involved in apoptosis signaling and betanin (20 and 50 µM), could decrease the apoptosis. The results show that betanin has antioxidant and anti-apoptotic effects and may have the ability to prevent or delay the progress of neural death in Parkinson's disease.

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Acknowledgements

The authors would like to thank Mr. Malaeke for assistance in the flow cytometry of samples.

Funding

This work has been supported by Grant No. 3/42879 from Ferdowsi University of Mashhad, Mashhad, Iran and Grant No. 951766 from Research Affairs of Mashhad University of Medical Sciences, Mashhad, Iran.

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EH performed the experiments and wrote the manuscript. MF and ZT-N conceived, designed, and supervised the project, wrote the manuscript nd provided financial support.

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Correspondence to Zahra Tayarani-Najaran.

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There is no conflict of interest in this study.

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As this work is carried out in PC12 cells, there is no need for ethical clearance.

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Hadipour, E., Fereidoni, M. & Tayarani-Najaran, Z. Betanin Attenuates Oxidative Stress Induced by 6-OHDA in PC12 Cells via SAPK/JNK and PI3 K Pathways. Neurochem Res 45, 395–403 (2020). https://doi.org/10.1007/s11064-019-02927-w

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  • DOI: https://doi.org/10.1007/s11064-019-02927-w

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