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Dihydromyricetin Protects Against Ethanol-Induced Toxicity in SH-SY5Y Cell Line: Role of GABAA Receptor

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Abstract

Toxicity induced by binge alcohol drinking, particularly in adolescent and young adults, is of major medical and social consequence. Recently, we reported that butyrate, a short chain fatty acid, can protect against ethanol (ETOH)-induced toxicity in an in vitro model. In this study, we sought to evaluate the potential effectiveness of dihydromyricetin (DHM), a natural bioactive flavonoid, alone or in combination with butyrate in the same model. Exposure of SH-SY5Y cells for 24 h to 500 mM ETOH resulted in approximately 40% reduction in cell viability, which was completely prevented by 0.1 μM DHM. Combinations of DHM and butyrate provided synergistic protection against alcohol toxicity. Whereas butyrate effect was shown to be mediated primarily through fatty acid receptor 3 activation, DHM protection appears to be mediated primarily via benzodiazepine receptor site of GABAA receptor. This is based on the finding that DHM’s effect could be completely prevented by pretreatment with flumazenil, a selective antagonist at this site, but not by bicuculline, a selective antagonist at the actual GABAA receptor binding site. These findings suggest potential utility of DHM alone or in combination with butyrate against ETOH-induced toxicity.

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Funding

This study is supported by NIH/NIAAA R03AA022479 (YT) and NIA/NIH 1R25AG047843-01 (ABC).

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Authors and Affiliations

  1. Department of Pharmacology, Howard University College of Medicine, 520 W Street NW, Washington, DC, USA

    Bruk Getachew & Yousef Tizabi

  2. Department of Anatomy, Howard University College of Medicine, 520 W Street NW, Washington, DC, USA

    Antonei B. Csoka

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  1. Bruk Getachew
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  2. Antonei B. Csoka
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  3. Yousef Tizabi
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Contributions

YT initiated the project idea and discussed with BG and ABC who further contributed to the design of the project. BG and ABC did the experiments, and the results were analyzed by YT, BG, and ABC. BG provided the first draft, which was edited by YT and approved by all the authors.

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Correspondence to Yousef Tizabi.

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Getachew, B., Csoka, A.B. & Tizabi, Y. Dihydromyricetin Protects Against Ethanol-Induced Toxicity in SH-SY5Y Cell Line: Role of GABAA Receptor. Neurotox Res 40, 892–899 (2022). https://doi.org/10.1007/s12640-022-00503-9

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