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

Autor: Getachew B; Department of Pharmacology, Howard University College of Medicine, 520 W Street NW, Washington, DC, USA., Csoka AB; Department of Anatomy, Howard University College of Medicine, 520 W Street NW, Washington, DC, USA., Tizabi Y; Department of Pharmacology, Howard University College of Medicine, 520 W Street NW, Washington, DC, USA. ytizabi@howard.edu.
Jazyk: angličtina
Zdroj: Neurotoxicity research [Neurotox Res] 2022 Jun; Vol. 40 (3), pp. 892-899. Date of Electronic Publication: 2022 Apr 07.
DOI: 10.1007/s12640-022-00503-9
Abstrakt: 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 GABA A 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 GABA A receptor binding site. These findings suggest potential utility of DHM alone or in combination with butyrate against ETOH-induced toxicity.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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