POTENTIATION OF CARBON TETRACHLORIDE-INDUCED LIVER-DAMAGE BY DIBUTYLYL-3',5'-CYCLIC AMP IN UNSTARVED RATS

It has been reported that carbon tetrachloride-induced liver damage is potentiated by starvation partly due to fat accumulation in the liver and a decrease in hepatic reduced glutathione concentration and that dibutylyl-3',5'-cyclic AMP (DBcAMP) affects fuel metabolism and decrea ses hepatic reduced glutathione. We investigated the effects of DBcAMP on carbon tetrachloride-induced liver damage both in unstarved and st arved rats. In unstarved rats, intraperitoneal administration of DBcAM P potentiated an increase in serum alanine aminotransferase activity a nd fatty vacuolization in the liver, both of which were induced by car bon tetrachloride. Hepatic reduced glutathione concentration was also reduced by DBcAMP, although the change was not significant. In contras t, the administration of DBcAMP in starved rats did not affect carbon tetrachloride-induced changes in serum alanine aminotransferase activi ty, histological alterations and hepatic reduced glutathione concentra tion. Administration of DBcAMP to control rats induced different respo nses in unstarved control rats compared with starved control rats: in unstarved rats, blood glucose concentration decreased but serum free f atty acid concentration increased, whereas in starved rats, blood gluc ose concentration increased and serum free fatty acid concentration de creased. It was suggested that DBcAMP potentiated carbon tetrachloride -induced liver damage in unstarved rats, probably due to hepatic fat a ccumulation and a decreased hepatic reduced glutathione concentration. The former could increase the affinity of the liver for carbon tetrac hloride and the latter could accelerate carbon tetrachloride-induced l ipid peroxidation. It was also suggested that DBcAMP failed to affect carbon tetrachloride-induced liver damage in starved rats, probably be cause starvation had already decreased hepatic glutathione concentrati on and DBcAMP had different effects on fuel metabolism compared with e ffects observed in unstarved rats.