chondroitin and Chemical-and-Drug-Induced-Liver-Injury

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.

Topics: Animals; Chemical and Drug Induced Liver Injury; Chondroitin; Chondroitin Sulfates; Dermatan Sulfate; Galactosamine; Glycosaminoglycans; Heparitin Sulfate; Hepatectomy; Liver; Liver Regeneration; Male; Polysaccharides; Rats

The extractable and nonextractable collagen and glycosaminoglycuronans (GAG) were estimated and characterized in 32 dried, defatted human livers obtained at necropsy. 10 had normal livers. 22 of the 32 livers were from patients who drank in excess: 5 had fatty livers, 7 had alcholic hepatitis, and 10 had cirrhosis. Livers with alcoholic hepatitis or cirrhosis had significantly increased total and 1 N NaCl-extractable collagen. Only alcoholic hepatitis livers had significantly increased Tris-buffer-extractable GAG, but the amino acid composition of these GAG (proteoglycans) was no different from that of normal livers. The major fraction of these GAG had isoelectric pH (pI)

Topics: Alcoholism; Amino Acids; Chemical and Drug Induced Liver Injury; Chondroitin; Chromatography, Gel; Collagen; Connective Tissue; Dialysis; Fatty Liver; Glucosamine; Glycoproteins; Glycosaminoglycans; Heparitin Sulfate; Hexosamines; Humans; Hyaluronic Acid; Hydroxyproline; Isoelectric Focusing; Liver; Liver Cirrhosis