title: Synthetic capacity and cell metabolites of bile duct obstructed rat livers. Effect of free and conjugated dihydroxy bile acids.
abstract: Morphologic alterations in liver cells after bile duct ligation are well known and documented in numerous reports. Biochemical studies concerning metabolic changes in cholestatic liver are rare. Therefore, in this study, liver cell metabolites and the capacity of the perfused cholestatic rat liver to produce glucose, urea and ketone bodies were measured. In addition the influence of dihydroxy bile acids on normal and bile duct ligated rat livers was studied. Concentrations of adenine nucleotides, lactate, pyruvate, 3-hydroxybutyrate, acetoacetate, glucose and UDP-glucose were found to be identical in cholestatic and normal livers. Glycogen content, however, was significantly lowered in cholestatic livers. Gluconeogenesis from lactate and urea production from ammonium chloride were only slightly reduced in bile duct obstructed rat livers. Dihydroxy bile acids did not affect the metabolism of normal or cholestatic livers. Ketone body production from oleate was reduced to 66% in bile duct obstructed livers, taurochenodeoxycholate further reduced this value to the normal value. In contrast to earlier reports (Fisher and co-workers, 1971 Lab. Invest. 21; 88-91; Gastroenterology 60: 742) chenodeoxycholate induced neither cholestasis nor a marked fall in ATP content or rat liver in our experiments with female Wistar rats. In conclusion, dihydroxy bile salts did exert toxic short term effects on rat livers.
mesh_terms: D000090:Acetoacetates / Q000378:metabolism; D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D002779:Cholestasis / Q000378:metabolism*; D002793:Cholic Acids / Q000494:pharmacology*; D003135:Common Bile Duct / Q000502:physiology; D003840:Deoxycholic Acid / Q000494:pharmacology; D005260:Female; D005943:Gluconeogenesis / Q000187:drug effects; D006003:Glycogen / Q000378:metabolism; D006885:Hydroxybutyrates / Q000378:metabolism; D007657:Ketone Bodies / Q000096:biosynthesis; D008026:Ligation; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D014508:Urea / Q000096:biosynthesis
chemical_list: D000090:Acetoacetates; D000227:Adenine Nucleotides; D002793:Cholic Acids; D006885:Hydroxybutyrates; D007657:Ketone Bodies; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D014508:Urea; D006003:Glycogen