Pivotal role of Kupffer cells in alcohol-induced liver injury: Increased susceptibility to alcohol in female rats

It is known that women develop hepatic injury more rapidly and with exposure to less ethanol than men; however, mechanisms remain unclear. Previous work from this group has demonstrated that destruction of Kupffer cells with gadolinium chloride or sterilization of the gut with antibiotics blocked alcohol-induced liver injury in male rats. The purpose of this study was to determine if a new model to study female susceptibility to alcohol-induced liver injury could be developed. Male and female Wistar rats were given ethanol (11 to 12 g/kg/day) continuously for up to 4 weeks via intragastric feeding while control rats received a high-fat diet without ethanol. In females, AST increased more rapidly and reached significantly higher Values at 4 weeks than males. Steatosis, inflammation, and necrosis also developed more rapidly and were more seven in females than males. Moreover, endotoxin in plasma, ICAM-1 expression in sinusoidal lining cells, and the number of infiltrating neutrophils in the liver were 2-2.5-fold greater in females than males. This most likely accounts for increased hepatic injury due to ethanol in the female.