title: Acute alcohol produces hypoxia directly in rat liver tissue in vivo: role of Kupffer cells.
abstract: Previous studies using liver slices and isolated perfused rat liver have suggested that ethanol causes hypoxia by increasing oxygen consumption. However, ethanol also increases blood flow to the liver, a phenomenon that may counteract the effects of hypermetabolism by increasing oxygen delivery. Thus whether ethanol causes hypoxia in vivo remains unclear. To clarify this important point, female Sprague-Dawley rats (100-125 g) simultaneously received pimonidazole (120 mg/kg ip), a 2-nitroimidazole hypoxia marker, and one large dose of ethanol (5 g/kg ig), which increase hepatic oxygen uptake dramatically and elevate ethanol metabolism (swift increase in alcohol metabolism) in 2-3 h. After 2 h, ethanol significantly increased the accumulation of bound pimonidazole in pericentral regions of the liver lobule. Treatment of animals with the Kupffer cell-specific toxicant, GdCl3 (10 mg/kg iv, 24 h before experiment), blocked ethanol-induced increases in pimonidazole binding. It is concluded that one large dose of ethanol causes pericentral hypoxia in rat liver tissue in vivo and that Kupffer cells are involved.
authors.affiliation: Department of Pharmacology, University of North Carolina, Chapel Hill 27599-7365, USA.
authors.forename: G E
authors.initials: GE
authors.lastname: Arteel
authors.forename: J A
authors.initials: JA
authors.lastname: Raleigh
authors.forename: B U
authors.initials: BU
authors.lastname: Bradford
authors.forename: R G
authors.initials: RG
authors.lastname: Thurman
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D007728:Kupffer Cells / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000431:Ethanol