Female rats exhibit greater susceptibility to early alcohol-induced
liver injury than males.
Iimuro, Yuji, Moritz V. Frankenberg, Gavin E. Arteel, Blair U.
Bradford, Chantal A. Wall, and Ronald G. Thurman.
Laboratory of Hepatobiology and Toxicology, Department of
Pharmacology, The University of North Carolina at Chapel Hill, Chapel
Hill, NC 27599-7365
APStracts 3:0275G, 1996.
It is known that women develop hepatic injury more rapidly and with
exposure to less ethanol than men; however, mechanisms remain
unclear. The purpose of this study was to determine if an enteral
alcohol delivery model could be used to study susceptibility of
females to alcohol-induced liver injury. Male and female Wistar rats
(age- or weight-matched) were given ethanol (11-12 g/kg/day)
continuously for up to 4 weeks via intragastric feeding while control
rats received a high-fat diet without ethanol. There were no
significant differences in body weight among the groups studied.
Further, mean ethanol concentrations, their cyclic pattern in urine,
and rates of ethanol elimination were also not different between the
genders under these conditions. Ethanol treatment elevated serum AST
levels in male rats to 126 +/- 10 IU/L after 4 weeks. In females,
however, values increased more rapidly and reached significantly
higher values at 4 weeks (168 +/- 18 IU/L). Steatosis, inflammation,
and necrosis assessed histologically also developed more rapidly and
were more severe in females than males. Steatosis due to ethanol
exposure, which was localized in centrilobular areas in males, was
panlobular in the female. Moreover, endotoxin in plasma, ICAM-1
expression in hepatic sinusoidal-lining cells, and the number of
infiltrating inflammatory cells in the liver were 2-2.5-fold greater
in females than males. These changes possibly account for increased
hepatic injury due to ethanol in the female.
Received 12 July 1996; accepted in final form 17 December 1996.
APS Manuscript Number G259-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996