Severity of liver injury in experimental alcoholic liver disease: Correlation with plasma endotoxin, prostaglandin E₂, leukotriene B₄, and thromboxane B₂

The purpose of our study is to determine if a relationship exists between the severity of injury in experimental alcoholic liver disease and plasma levels of endotoxin, prostaglandin E₂, leukotriene B₄, and thromboxane B₂. Four groups of animals (n = 4 to 8 in each group) were fed a liquid diet with corn oil (25% of calories) and ethanol over various time periods: 1 week, 2 weeks, 1 month, and 2 months. At sacrifice, liver pathology scores and plasma levels of the above were determined. Plasma levels of endotoxin were already increased after 1 week (26.6 ± 18.6 pg/ml) and continued to increase over time, with the highest levels at 2 months (69.5 ± 24.5 pg/ml). A strong positive correlation (r = 0.84, P < 0.001) was seen between plasma endotoxin levels and severity of liver injury. The pathology score also correlated positively with leukotriene B₄ (r = 0.47, P < 0.05) and thromboxane B₂ (0.66, P < 0.01). A negative correlation was obtained with prostaglandin E₂ levels (r = -0.44, P < 0.05). A positive correlation was also seen between endotoxin levels and leukotriene B₄ (r = 0.57, P < 0.02) and thromboxane B₂ (0.64, P < 0.01); a negative correlation was obtained with prostaglandin E₂ levels (r = -0.55, P < 0.02). Each metabolite was also correlated with each of the features of alcoholic liver injury, i.e., fatty liver, necrosis, and inflammation. With prostaglandin E₂, the most marked decrease was seen in association with severe fatty liver (3 to 4+). Thromboxane B₂ correlated best with presence of inflammation and necrosis. Our study shows the importance of endotoxin in the pathogenesis of experimental alcoholic liver disease and suggests that endotoxin modulates production of eicosanoids that contribute to the severity of liver injury.