THE LIMITING EFFECT OF DICHLOROACETATE ON ENDOTOXIN-INDUCED LIVER-DAMAGE IN STARVED RATS

Dichloroacetate has been shown to have therapeutic effects on sepsis a nd endotoxin shock and to reduce liver damage in rats intoxicated with ethanol or carbon tetrachloride. In this study, the effect of dichlor oacetate on endotoxin hepatitis was investigated. Endotoxin hepatitis was induced by an intraperitoneal coadministration of 50 mu g/kg lipop olysaccharide from Escherichia coli, and 200 mg/kg D-galactosamine in starved, male Wistar rats. This treatment induced the following change s within 24 hr: an increase in the serum aminotransferase activity, hi stological alterations of the liver including focal necrosis of liver cells and inflammatory infiltrates, an increase in blood pyruvate and alanine concentrations, and inhibition of starvation ketosis. The intr aperitoneal administration of 250 mg/kg dichloroacetate 30 min after t he administration of the toxins partially counteracted all of these ch anges. The administration of dichloroacetate might be useful in coping with hepatic damage as well as lacticemia and cardiovascular depressi on induced by endotoxins. (C) 1994 Academic Press, Inc.