title: Phenolic compounds protect cultured hippocampal neurons against ethanol-withdrawal induced oxidative stress.
abstract: Ethanol withdrawal is linked to elevated oxidative damage to neurons. Here we report our findings on the contribution of phenolic antioxidants (17beta-estradiol, p-octyl-phenol and 2,6-di-tert-butyl-4-methylphenol) to counterbalance sudden ethanol withdrawal-initiated oxidative events in hippocampus-derived cultured HT-22 cells. We showed that ethanol withdrawal for 4 h after 24-h ethanol treatment provoked greater levels of oxidative damage than the preceding ethanol exposure. Phenolic antioxidant treatment either during ethanol exposure or ethanol withdrawal only, however, dose-dependently reversed cellular oxidative damage, as demonstrated by the significantly enhanced cell viability, reduced malondialdehyde production and protein carbonylation, compared to untreated cells. Interestingly, the antioxidant treatment schedule had no significant impact on the observed neuroprotection. In addition, the efficacy of the three phenolic compounds was practically equipotent in protecting HT-22 cells in spite of predictions based on an in silico study and a cell free assay of lipid peroxidation. This finding implies that free-radical scavenging may not be the sole factor responsible for the observed neuroprotection and warrants further studies to establish, whether the HT-22 line is indeed a suitable model for in vitro screening of antioxidants against EW-related neuronal damage.
authors.affiliation: Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: Katalin
authors.initials: K
authors.lastname: Prokai-Tatrai
authors.affiliation: Department of Molecular Biology & Immunology, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Prokai
authors.affiliation: Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Simpkins
authors.affiliation: Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: Marianna E
authors.initials: ME
authors.lastname: Jung
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D010636:Phenols; D000431:Ethanol