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 decreases hepatic reduced glutathione. We investigated the effects of DBcAMP on carbon tetrachloride-induced liver damage both in unstarved and starved rats. In unstarved rats, intraperitoneal administration of DBcAMP potentiated an increase in serum alanine aminotransferase activity and fatty vacuolization in the liver, both of which were induced by carbon tetrachloride. Hepatic reduced glutathione concentration was also reduced by DBcAMP, although the change was not significant. In contrast, the administration of DBcAMP in starved rats did not affect carbon tetrachloride-induced changes in serum alanine aminotransferase activity, histological alterations and hepatic reduced glutathione concentration. Administration of DBcAMP to control rats induced different responses in unstarved control rats compared with starved control rats: in unstarved rats, blood glucose concentration decreased but serum free fatty acid concentration increased, whereas in starved rats, blood glucose concentration increased and serum free fatty acid concentration decreased. It was suggested that DBcAMP potentiated carbon tetrachloride-induced liver damage in unstarved rats, probably due to hepatic fat accumulation and a decreased hepatic reduced glutathione concentration. The former could increase the affinity of the liver for carbon tetrachloride and the latter could accelerate carbon tetrachloride-induced lipid peroxidation. It was also suggested that DBcAMP failed to affect carbon tetrachloride-induced liver damage in starved rats, probably because starvation had already decreased hepatic glutathione concentration and DBcAMP had different effects on fuel metabolism compared with effects observed in unstarved rats.
Irita
K
K
Department of Anesthesiology and Critical Care Medicine, Kyushu University School of Medicine, Fukuoka, Japan.
Okabe
H
H
Yamakawa
M
M
Yoshitake
J
J
Takahashi
S
S
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003994:Bucladesine / Q000008:administration & dosage / Q000494:pharmacology*; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism* / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury; D004357:Drug Synergism; D005227:Fatty Acids / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013217:Starvation / Q000378:metabolism
D001786:Blood Glucose; D005227:Fatty Acids; D003994:Bucladesine; D000410:Alanine Transaminase; D005978:Glutathione