Effect of adenosine 3',5'-cyclic monophosphate derivatives on acute liver injury induced by carbon tetrachloride.
The inhibitory effects of 12 synthetic N6-alkyl cAMPs, 8-substituted cAMPs and cAMP alkylphosphoramidate derivatives (50 or 100 mg/kg, bolus, i.p.) on serum GOT and GPT activities and hepatocyte cytoplasmic vacuolation were examined in male Fischer 344 rats, which were exposed to CCl4 (0.5 mg/kg, p.o.) 30 min prior to the administration of cAMP derivatives. In CCl4-treated rats 6 h later, serum GOT and GPT levels were elevated 10- and 12-fold higher than those of vehicle rats, respectively. Treating CCl4-exposed rats with all cAMP derivatives, except those of alkylphosphoramidate, significantly decreased the levels of serum enzymes. Based on the effects of both serum GOT and GPT elevation, N6-butyl- and N6-heptyl-cAMP were the most potent. It was also observed histopathologically, that both compounds inhibited the occurrence of cytoplasmic vacuolation in CCl4-treated liver cells. This is the first report that cAMP derivatives possess a protective effect in the liver injury model induced by CCl4.
Saito
M
M
Noda Institute for Scientific Research, Chiba, Japan.
Nasu
A
A
Kataoka
S
S
Yamaji
N
N
Ichikawa
A
A
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000648:ultrastructure; D008099:Liver / Q000187:drug effects* / Q000648:ultrastructure; D008107:Liver Diseases / Q000473:pathology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure
D002251:Carbon Tetrachloride; D000242:Cyclic AMP; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase