title: The Dietary Flavonoid Rhamnetin Inhibits Both Inflammation and Excitotoxicity During Ethanol Withdrawal in Rat Organotypic Hippocampal Slice Cultures.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Lutz
authors.affiliation: Department of Psychology, College of Arts and Sciences, University of Kentucky, Lexington, Kentucky.
authors.forename: Megan
authors.initials: M
authors.lastname: Carter
authors.affiliation: Department of Psychology, College of Arts and Sciences, University of Kentucky, Lexington, Kentucky.
authors.forename: Logan
authors.initials: L
authors.lastname: Fields
authors.affiliation: Department of Psychology, College of Arts and Sciences, University of Kentucky, Lexington, Kentucky.
authors.forename: Susan
authors.initials: S
authors.lastname: Barron
authors.affiliation: Department of Psychology, College of Arts and Sciences, University of Kentucky, Lexington, Kentucky.
authors.forename: John M
authors.initials: JM
authors.lastname: Littleton
mesh_terms: D000818:Animals; D000431:Ethanol / Q000633:toxicity*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D009924:Organ Culture Techniques; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism
chemical_list: D018690:Excitatory Amino Acid Agonists; D005419:Flavonoids; D018836:Inflammation Mediators; D000431:Ethanol; C063423:rhamnetin; D011794:Quercetin
keywords: Alpha7 Nicotinic Acetylcholine Receptors; Ethanol-Induced Neurotoxicity; Excitotoxicity; Neuroinflammation; Rhamnetin