Protective effects ofcholestyramine on liver cirrhosis induced bycarbon tetrachloride intherat

SUMMARY Theinfluence ofcholestyramine andchenodeoxycholic acid on theinduction ofliver cirrhosis bycarbon tetrachloride was investigated intheWistar rat.Theaddition of1.3% cholestyramine tothediet oftheexperimental animals inhibited toalarge extent theinduction ofcirrhosis. Whileall theanimals subjected tocarbon tetrachloride exposureplus basal diet andthose tocarbon tetrachloride intoxication pluschenodeoxycholic aciddiet developed cirrhosis, themorphological manifestation ofcirrhosis occurred inthelivers ofonly twooutof18ratsundercarbon tetrachloride treatment plus cholestyramine diet. Theadministration ofcholestyramine induces reactions which correspond tothephysiological protective mechanisms oftheliver. These arethebile acidbinding, bacteriostatic, andmicrosomal enzymatic stimulating properties ofcholestyramine. Thecentral role oftheliver inmetabolism ofthebile acids includes thesynthesis, conjugation, andthe maintenance oftheintegrity oftheenterohepatic circulation. Thecontrol ofthesize andcomposition ofthebile acidpoolandthedetoxification ofnoxiousintermediate products fromtheintestinal tract ismodified andregulated bythehepatocytes. These functions aremoreorless impaired during cirrhosis orother diseases oftheliver. Consequently thetoxic bileacids, especially thesecondary bileacids, lithocholic anddeoxycholic acids, intheenterohepatic circulation arenotdetoxified.'-3 Whether thedisturbed bile acid metabolism hasaninfluence ontheimpaired liver hasonlybeeninvestigated to alimited extent. Furthermore, thepathogenic effects ofseveral intermediate products ofbile acidmetabolism have beenexperimentally verified.4-8 ThusHolsti induced liver cirrhosis intherabbit byoral administration of desiccated wholebile preparation9 andbygastric instillation oflithocholic acid.10 Thequestion that particularly interests us,therefore, iswhether theoralapplication ofchenodeoxycholic acid(CDCA),themainsource of lithocholic acid, andcholestyramine (CT), aquaternaryammoniumanion exchange resin, whichhasa strong affinity forbile salts intheintestine andthus prevents their enteral resorption, hasaninfluence on