EFFECT OF ADENOSINE 3', 5'-CYCLIC MONOPHOSPHATE DERIVATIVES ON ACUTE LIVER INJURY INDUCED BY CARBON TETRACHLORIDE

Abstract

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 CCI₄ (0.5 mg/kg, p. o.) 30 min prior to the administration of cAMP derivatives. In CCI₄-treated rats 6 h later, serum GOT and GPT levels were elevated 10-and 12-fold higher than those of vehicle rats, respectively . Treating CCI₄-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 CCI₄-treated liver cells. This is the first report that cAMP derivatives possess a protective effect in the liver injury model induced by CCI₄.