Synthesis of hepatic glycosaminoglycans in the early stages of galactosamine hepatitis: a rapid decline of heparan sulfate is followed by elevation of chondroitin sulfate and dermatan sulfate.
Administration of a single dose of D-galactosamine to rats causes time-dependent, biphasic changes of total glycosaminoglycan synthesis in liver. A rapidly occurring inhibition is followed by a significantly enhanced (greater than 2 fold) production of 35S-labeled glycosaminoglycans in later stages of injury. Degree and duration of the inhibitory phase are dose-dependent; 50% inhibition is reached at 80 mg/kg and maximum inhibition (nearly 80%) at about 300 mg/kg body weight 2 h after injection of D-galactosamine. The hepatotoxin impairs preferentially the production of heparan sulfate, whereas that of chondroitin sulfate and dermatan sulfate is diminished only slightly and for a rather short period of time. The synthesis of the latter, however, is more stimulated than that of heparan sulfate in later stages of injury. The specific radioactivity of 35S-labeled 3'-phosphoadenosine-5'-phosphosulfate (PAPS) did not change significantly during the course of acute liver damage. Glycosaminoglycan synthesis in regenerating liver was nearly unaffected by D-galactosamine. Uridine at the dose applied partially reversed D-galactosamine-inhibited synthesis of proteoheparan sulfate. In accordance with the labeling studies the content of glucosamine-containing glycosaminoglycans in treated liver decreased, whereas that of galactosamine-containing glycosaminoglycans slightly increased, resulting in a nearly 50% reduction of the glucosamine/galactosamine ratio 5 h after administration of D-galactosamine. Ion exchange chromatographic studies of 35S-labeled specific types of glycosaminoglycans from normal and galactosamine-injured liver revealed only minor structural differences.
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D002807:Chondroitin / Q000031:analogs & derivatives*; D002809:Chondroitin Sulfates / Q000378:metabolism*; D003871:Dermatan Sulfate / Q000378:metabolism*; D005688:Galactosamine / Q000031:analogs & derivatives / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis* / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D006498:Hepatectomy; D008099:Liver / Q000378:metabolism*; D008115:Liver Regeneration; D008297:Male; D011134:Polysaccharides / Q000378:metabolism; D051381:Rats
D002807:Chondroitin; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D005688:Galactosamine; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D011134:Polysaccharides; C007815:galactosaminoglycan