Stereological and functional analysis of liver mitochondria from rats with secondary biliary cirrhosis: impaired mitochondrial metabolism and increased mitochondrial content per hepatocyte.
Mitochondrial and cytosolic functions were studied in vivo and in perfused livers from rats with secondary biliary cirrhosis induced by bile duct ligation for 5 wk and in sham-operated controls. The livers were stereologically analyzed, and mitochondrial and cytosolic functions were related to liver structure. Oxygen consumption by perfused livers expressed per stereologically determined mitochondrial volume was decreased by 49% in bile duct-ligated rats compared with control rats. Glucose production (expressed per mitochondrial volume) was reduced by more than 90% in bile duct ligation, whereas urea production was not affected. Lactate production, a cytosolic function, was increased fivefold in bile duct ligation, and both the lactate/pyruvate and the beta-hydroxybutyrate/aceto-acetate ratios were increased in the liver perfusate of bile duct-ligated rats. In comparison with control rats, the stereologically determined mitochondrial volume fraction per hepatocyte was increased by 28% in bile duct-ligated rats. Activities of mitochondrial enzymes expressed per area of mitochondrial membrane or per mitochondrial volume were either unchanged (ATPase, cytochrome c oxidase and glutamate dehydrogenase) or decreased (monoamine oxidase) in bile duct ligation. Thus in comparison with control rats, mitochondrial metabolism is impaired in perfused livers from bile duct-ligated rats; increased mitochondrial volume per hepatocyte may represent a strategy to maintain hepatic energy metabolism in rats with secondary biliary cirrhosis.
Krähenbühl
S
S
Department of Clinical Pharmacology, University of Berne, Switzerland.
Krähenbühl-Glauser
S
S
Stucki
J
J
Gehr
P
P
Reichen
J
J
D000818:Animals; D001652:Bile Ducts; D003600:Cytosol / Q000502:physiology; D005947:Glucose / Q000096:biosynthesis; D066298:In Vitro Techniques; D007773:Lactates / Q000096:biosynthesis; D008026:Ligation; D008099:Liver / Q000648:ultrastructure*; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains
D007773:Lactates; D005947:Glucose