Dichloroacetate-lnduced Changes in Liver of Normal and Diabetic Rats

Dichloroacetate (DCA) was administered orally to normal (nondiabetic) and streptozotocin-diabetic rats in a dose of 1000 mg/day/kg rat wt. One group of diabetic animals Received DCA both orally and intraperitoneally. DCA therapy lowered the blood glucose values of diabetic animals but did not alter values in nondiabetic rats. The hepatic activity of glucokinase and pyruvate kinase were significantly lower in both DCA-treated nondiabetic and DCA-treated diabetic animals than values observed for untreated animals. However, DCA therapy was accompanied by remarkable increases in the activities of glucose-6-phosphate dehydrogenase and malic enzyme in both nondiabetic and diabetic animals. Glucose-6-phosphate dehydrogenase was 3-fold higher in DCA-treated nondiabetic animals whereas malic enzyme activity was 10-fold higher in the treated animals than observed in the untreated animals. Similar changes, although smaller in magnitude, were observed for these enzymes in the DCA-treated diabetic animals. Although DCA therapy was accompanied by a significant increase in the wet weights of the liver for both nondiabetic and diabetic animals, no morphological changes were seen by light or electron microscopy. Our observations coupled with those of previous investigators suggest that DCA therapy may have an important role in pyruvate metabolism and may lower the blood glucose concentration by inhibiting hepatic gluconeogenesis.