Plasma amino acids in long-term models for obstructive versus toxic liver injury in developing rats.
We evaluated plasma amino acid (AA) concentrations associated with a histologically defined lesion caused by bile duct ligation (BDL) in developing rats. Nineteen rats that underwent BDL at 14 days of age had marked bile duct proliferation with bridging fibrosis, multifocal lobular necrosis, and minimal polymorphonuclear periportal infiltrate in their livers at sacrifice (11-31 days after ligation). These were compared to two age-matched control groups: 21 nonoperated rats and 22 sham-operated rats; and eight rats with cirrhosis caused by carbon tetrachloride. Signs of liver damage including jaundice, growth failure, bleeding, and ascites were accompanied by elevated bilirubin, ammonia, aspartate aminotransferase (AST), and alkaline phosphatase levels in BDL rats compared to controls. They had higher concentrations of total AAs, phenylalanine, tyrosine, and cyst(c)ine when compared to controls and to CCl4-treated rats. Micronodular cirrhosis was present in CCL4-treated rats with elevated AST and alkaline phosphatase levels. Glutamine and glutamate levels were higher in them than in BDL rats or controls, and branched chain AA levels were lower. These two chronic lesions, one obstructive and one hepatotoxic, both result in fibrotic change, but their metabolic abnormalities as reflected in plasma AA levels are distinct. We found that BDL is an appropriate model with which to study metabolic changes and growth failure due to chronic biliary stasis during its progression to frank cirrhosis.
Weisdorf
S A
SA
Department of Pediatrics, University of Minnesota, Minneapolis.
Freese
D K
DK
Radmer
W J
WJ
Dehner
L P
LP
Cerra
F B
FB
D000596:Amino Acids / Q000097:blood*; D000818:Animals; D000833:Animals, Suckling / Q000097:blood*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D002779:Cholestasis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids