title: Role of endotoxin in the hypermetabolic state after acute ethanol exposure.
abstract: This study investigated the role of endotoxin in the hypermetabolic state or swift increase in alcohol metabolism (SIAM) due to acute ethanol exposure. Female Sprague-Dawley rats (100-120 g) were given ethanol (5 g/kg) by gavage. Endotoxin measured in plasma from portal blood was not detectable in saline-treated controls; however, 90 min after ethanol, endotoxin was increased to 85 +/- 14 pg/ml, and endotoxin clearance was diminished by approximately 50%. Oxygen uptake in perfused livers was increased 48% by ethanol, and production of PGE2 by isolated Kupffer cells was increased similarly. These effects were blunted by elimination of gram-negative bacteria and endotoxin with antibiotics before ethanol administration. To reproduce ethanol-induced endotoxemia, endotoxin was infused via the mesenteric vein at a rate of 2 ng. kg-1. h-1. Endotoxin mimicked the effect of ethanol on oxygen uptake. The specific Kupffer cell toxicant GdCl3 completely prevented increases in oxygen uptake due to endotoxin. These findings demonstrate that endotoxin plays a pivotal role in SIAM, most likely by stimulating eicosanoid release from Kupffer cells.
authors.affiliation: Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Rivera
authors.forename: B U
authors.initials: BU
authors.lastname: Bradford
authors.forename: V
authors.initials: V
authors.lastname: Seabra
authors.forename: R G
authors.initials: RG
authors.lastname: Thurman
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D004731:Endotoxins / Q000097:blood / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005682:Gadolinium / Q000494:pharmacology; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008660:Metabolism / Q000187:drug effects* / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
chemical_list: D000900:Anti-Bacterial Agents; D004731:Endotoxins; D000431:Ethanol; D005682:Gadolinium; D015232:Dinoprostone; C038958:gadolinium chloride