Role of endotoxin in the hypermetabolic state after acute ethanol exposure.
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.
Rivera
C A
CA
Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Bradford
B U
BU
Seabra
V
V
Thurman
R G
RG
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
D000900:Anti-Bacterial Agents; D004731:Endotoxins; D000431:Ethanol; D005682:Gadolinium; D015232:Dinoprostone; C038958:gadolinium chloride