title: Mechanisms of alcohol impairment of recovery from mechanically denuded areas made within cultured rat hepatocytes.
abstract: The effect of ethanol on the ability of a denuded hepatocyte cell surface to recover is unknown. We therefore determined the effect of ethanol on the rate of renewal of mechanical wounds made in near-confluent monolayers of primary cultures of rat hepatocytes. We found that ethanol exerted a dose-dependent effect to impair rat hepatocyte recovery and that at least 12 hours of exposure to ethanol was required to induce this impairment. The effect of ethanol to impair recovery of denuded areas of epithelium was not seen in two established renal tubular epithelial cell lines. Ethanol impairment of rat hepatocyte recovery could be blocked by an alcohol dehydrogenase inhibitor (4-methyl pyrazole) and potentiated by an inhibitor of aldehyde dehydrogenase (pargyline). The effect of ethanol to inhibit rat hepatocyte recovery of denuded areas was not associated with any change in hepatocyte cell surface expression of the beta1 integrin subunit as determined by flow cytometry. These results suggest that acetaldehyde is responsible for ethanol inhibition of hepatocyte recovery from mechanical injury and that this impairment occurs independent of cell surface expression of the beta1 integrin subunit.
authors.affiliation: Denver Veterans Affairs Medical Center and The Hepatobiliary Center, University of Colorado Health Sciences Center, 80220, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Anderson
authors.forename: H T
authors.initials: HT
authors.lastname: Sponsel
authors.forename: S E
authors.initials: SE
authors.lastname: Brown
authors.forename: R
authors.initials: R
authors.lastname: Breckon
authors.forename: C
authors.initials: C
authors.lastname: Ray
authors.forename: F R
authors.initials: FR
authors.lastname: Simon
authors.forename: P S
authors.initials: PS
authors.lastname: Guzelian
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000431:Ethanol / Q000378:metabolism / Q000633:toxicity*; D019012:Integrin beta1 / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D010293:Pargyline / Q000494:pharmacology; D051381:Rats
chemical_list: D019012:Integrin beta1; D000431:Ethanol; D010293:Pargyline