THE HEPATOTOXICITIES OF ENDOTOXIN AND ETHANOL - COMPARISONS IN-VITRO USING THE PRECISION-CUT RAT-LIVER SLICE MODEL

Using the precision-cut rat liver slice model, the in vitro toxicities of endotoxin and ethanol, independently and in combination, were eval uated. Hepatotoxicity was assessed by two measures: the leakage of LDH from slice to medium and the ability of slices to reduce a tetrazoliu m compound, MTT. Ethanol, in concentrations of 1% and greater, exhibit ed a time and dose dependent hepatotoxicity; MTT reductive capacity wa s more profoundly affected than LDH leakage. Endotoxin (0.1 to 100 mu g/ml), however, had only a modest effect on MTT reduction and did not perturb LDH leakage. When combined in vitro, the toxicities of 2% etha nol and various concentrations of endotoxin were additive. Slices prep ared from the livers of rats injected ip with endotoxin one day previo usly sustained considerably more injury (compared to normal rat liver slices) upon subsequent in vitro exposure to either endotoxin or ethan ol. Prior in vivo exposure to ethanol, however, did not affect the sub sequent in vitro toxicity of endotoxin. Thus, while endotoxin exhibits only subtle toxic effects upon liver slices in vitro, exposure to end otoxin in vivo renders the liver more susceptible to subsequent direct injury by endotoxin or ethanol.