Acute alcohol produces hypoxia directly in rat liver tissue in
vivo: role of kupffer cells.
Arteel, Gavin E., James A. Raleigh, Blair U. Bradford & Ronald G.
Thurman.
Laboratory of Hepatobiology and Toxicology, Department of
Pharmacology, Department of Radiation Oncology and 3Curriculum in
Toxicology, University of North Carolina at Chapel Hill, Chapel Hill,
NC 27599-7365
APStracts 3:0052G, 1996.
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 which 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 (100-125g) simultaneously received pimonidazole
(120 mg/kg i.p.), a 2-nitroimidazole hypoxia marker, and one large
dose of ethanol (5 g/kg i.g.) which increases hepatic oxygen uptake
dramatically and elevates ethanol metabolism [Swift Increase in
Alcohol Metabolism (SIAM)] in 2-3 hours. After two hours, ethanol
significantly increased the accumulation of bound pimonidazole in
pericentral regions of the liver lobule. Treatment of animals with
the Kupffer cell-specific toxicant, gadolinium chloride (10 mg/kg
i.v. 24 h prior to experiment), blocked ethanol-induced increases in
pimonidazole binding. Taken together, it is concluded that one large
dose of ethanol causes pericentral hypoxia in rat liver tissue in
vivo and that Kupffer cells are involved.
Received 13 September 1995; accepted in final form 26 February
1996.
APS Manuscript Number G407-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 March 96