PMID: 6170514Sep 1, 1981Paper

The effect of the hypocholesteremic drug, AY 9944 on the synthesis of bile salts in rat liver

European Journal of Biochemistry
K M Botham, G S Boyd

Abstract

1. The compound trans-1,4 bis-(2-dichlorobenzylaminomethyl)cyclohexane dihydrochloride (AY9944) blocks cholesterol synthesis at a late stage. This leads to a decrease in cholesterol and accumulation of cholesta-5,7-diene-3-beta-ol (7-dehydrocholesterol) in tissues and plasma. 2. The effect of AY9944 on bile salt synthesis in rat liver was studied. The synthesis of conjugated cholic and chenodeoxycholic acids was measured in hepatocytes isolated from rats 2 h, 24 h and 48 h after administration of a single oral dose of AY9944. Production of the two bile salts was inhibited by 70-80% in hepatocytes from AY9944-treated as compared to untreated animals. 3. When AY9944 was added to the incubation medium in vitro of hepatocytes prepared from untreated rats the synthesis of conjugated cholic and chenodeoxycholic acids was not inhibited during the first hour of incubation, probably because of the presence of endogenous cholesterol. However when hepatocytes from untreated rats were incubated with AY9944 for periods of 2 h or longer, bile salt production was decreased markedly. 4. Bile salt synthesis is stimulated when rats are subjected to total biliary drainage for 24 h. The effect of AY9944 on this stimulation was studied. The content...Continue Reading

References

Sep 1, 1978·Clinica Chimica Acta; International Journal of Clinical Chemistry·G J BeckettI W Percy-Robb
Apr 2, 1979·Clinica Chimica Acta; International Journal of Clinical Chemistry·G J BeckettI W Percy-Robb
Apr 1, 1979·European Journal of Biochemistry·K M Botham, G S Boyd
Aug 1, 1978·Canadian Journal of Biochemistry·I M YousefK N Jeejeebhoy
May 2, 1974·European Journal of Biochemistry·M J Brown, G S Boyd
Jun 9, 1972·European Journal of Biochemistry·N A Alam, J Glover
Jan 1, 1980·European Journal of Biochemistry·K M BothamG S Boyd
Jun 1, 1953·Proceedings of the Society for Experimental Biology and Medicine·J C THOMPSON, H M VARS
Mar 1, 1957·Proceedings of the Society for Experimental Biology and Medicine·S ERIKSSON

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