Cholestasis and changes of portal pressure caused by chlorpromazine in the perfused rat liver
Article first published online: 6 DEC 2005
Copyright © 1991 American Association for the Study of Liver Diseases
Volume 13, Issue 2, pages 216–221, February 1991
How to Cite
Akerboom, T., Schneider, I., vom Dahl, S. and Sies, H. (1991), Cholestasis and changes of portal pressure caused by chlorpromazine in the perfused rat liver. Hepatology, 13: 216–221. doi: 10.1002/hep.1840130204
- Issue published online: 6 DEC 2005
- Article first published online: 6 DEC 2005
- Manuscript Received: 18 DEC 1990
- Deutsche Forschungsgemeinschaft. Grant Number: Ak 8/1-2
Chlorpromazine (10 μmol/L) causes a marked increase in portal pressure in perfused rat liver. Simultaneously, oxygen consumption, hepatic clearance of taurocholate and bile flow are diminished. These effects are prevented by the cyclooxygenase inhibitors indomethacin (15 μmol/L), acetylsalicylate (3 mmol/L) or ibuprofen (200 μmol/L). On addition of chlorpromazine the liver releases increased amounts of prostaglandin D2; this increase does not occur in the presence of indomethacin.
At higher concentrations of chlorpromazine (100 μmol/L) the inhibition of taurocholate clearance and bile flow is accompanied by only a moderate increase of portal pressure, and indomethacin is without effect. At this high concentration, substantial cell damage, as indicated by the release of lactate dehydrogenase, is present.
We conclude that arachidonic acid—derived metabolites, notably prostanoids, are involved in the inhibition of bile flow and of taurocholate clearance observed at low concentrations of chlorpromazine. The data suggest that changes in the microcirculation are responsible for the impairment of the liver functions. At higher concentrations of chlorpromazine the cell toxicity of the drug becomes prominent. (HEPATOLOGY 1991;13:216–221).