The Dietary Flavonoid Rhamnetin Inhibits Both Inflammation and Excitotoxicity During Ethanol Withdrawal in Rat Organotypic Hippocampal Slice Cultures

Joseph A. Lutz, Megan Carter, Logan Fields, Susan Barron, John M. Littleton

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Background: Ethanol (EtOH) causes neurotoxicity via several mechanisms including neuroinflammation (during EtOH exposure), and excitotoxicity (during EtOH withdrawal [EWD]). Alpha7 nicotinic acetylcholine receptor (nAChR) selective agonists have the potential to reduce both. The aim of this study was to evaluate the anti-inflammatory and neuroprotective potential of rhamnetin, a dietary flavonoid with alpha7 nAChR selective activity, in an in vitro model of EtOH-induced neurotoxicity. Methods: The anti-inflammatory and neuroprotective properties of rhamnetin were assessed in neonatal organotypic hippocampal slice cultures undergoing EWD (or not) and challenged with N-methyl-D-aspartate (NMDA) and/or lipopolysaccharide (LPS). Neurotoxicity was determined using propidium iodide uptake, and the inflammatory response was evaluated by measuring the release of tumor necrosis factor (TNF)-alpha (NO; quantified by ELISA) and nitric oxide (quantified by the Griess reaction) into culture media. Results: As predicted, rhamnetin reduced LPS-induced release of TNF-alpha and NO both under control conditions and during EWD. Additionally, rhamnetin had no effect on NMDA-induced neurotoxicity under control conditions, but significantly reduced NMDA toxicity during EWD. In contrast, rhamnetin had no effect on neurotoxicity induced by NMDA and LPS combined despite reducing TNF-alpha and NO levels under these conditions. Conclusions: Rhamnetin is anti-inflammatory and neuroprotective during EWD and therefore has potential value in treating neurotoxicity caused by EtOH.

Original languageEnglish
Pages (from-to)2345-2353
Number of pages9
JournalAlcoholism: Clinical and Experimental Research
Issue number12
StatePublished - Dec 1 2015

Bibliographical note

Funding Information:
This work was supported in part by NIAAA (National Institute on Alcohol Abuse and Alcoholism) grants (R21- AA020188, R42-AA014555, and R42-AA015475) awarded to Dr. Littleton as Principal Investigator. The authors would like to thank Dr. Mark Prendergast for allowing use of his microscope. Dr. Littleton owns stock in NaprogenixTM and functions as Chief Scientific Officer. He was not involved in the collection or analysis of any data presented. The remaining authors have no other conflicts of interest to report.

Publisher Copyright:
© 2015 Research Society on Alcoholism.


  • Alpha7 nicotinic acetylcholine receptors
  • Ethanol-induced neurotoxicity
  • Excitotoxicity
  • Neuroinflammation
  • Rhamnetin

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health


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