Preventive effects of acute inflammation on liver cell necrosis and inhibition of heparan sulphate synthesis in hepatocytes.
The hepatocytoprotective effect of acute, turpentine-induced inflammation on experimental liver injury, caused by thioacetamide and D-galactosamine, respectively, was studied in relation to the synthesis of glycosaminoglycans and of heparan sulphate in hepatocytes isolated from livers of treated rats. As judged from biochemical parameters of liver cell lesion in serum (various cytosolic and mitochondrial enzymes, bile acids) the extent of liver damage caused by either noxious agent was greatly attenuated under acute inflammatory conditions. There was an inverse statistical correlation (r = -0.63 to r = -0.84) between the functional concentration of a proteinase inhibitor protein determined with the chromogenic substrate assay for human alpha 2-macroglobulin and the catalytic concentrations of various cell leakage enzymes in serum from liver-injured rats with turpentine-generated inflammation. The strong inhibition of heparan sulphate synthesis in hepatocytes from injured livers (synthesis rate between 0.2 and 0.4 of that in control cell incubations) is abolished in hepatocytes from livers exposed to the noxious agents but with acute inflammation. The latter condition alone caused a 1.8 fold increase in heparan sulphate synthesis of hepatocytes. Heparan sulphate was the only type of glycosaminoglycan synthesized under all conditions. The results are discussed in view of the pathogenetic potential of heparan sulphate for liver cell necrosis.
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D004247:DNA / Q000378:metabolism; D004798:Enzymes / Q000097:blood; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006493:Heparin / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009336:Necrosis; D011480:Protease Inhibitors / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D001647:Bile Acids and Salts; D004798:Enzymes; D006025:Glycosaminoglycans; D011480:Protease Inhibitors; D006493:Heparin; D004247:DNA