Changes in hepatic collagen metabolism in rats produced by chronic ethanol feeding

Feeding of ethanol to rats and baboons has been demonstrated to result in increases in collagen synthesis and deposition prior to any histologic evidence of hepatocellular necrosis or fibrosis. The purpose of this study was to determine the effect of chronic ethanol feeding, supplemented by weekly acute doses of ethanol for a period of 6 mth, on the deposition of fibrous and ground substance components of hepatic collagen and on parameters of collagen synthesis and degradation in the rat. In this animal, the prolonged feeding of ethanol has caused only partly infiltration of the liver, till now. In the presented 6 mth experiment ethanol feeding resulted in small increases in the fibrous and ground substance components of hepatic collagen as measured by increases in collagen bound hydroxyproline and hexosamine, respectively. Liver histology revealed fatty infiltration but no necrosis or fibrosis. The activity of collagen proline hydroxylase and the incorporation of labeled proline into collagen by liver slices, both of which are associated with collagen synthesis, were not changed. Ethanol feeding resulted in increases in the concentration of protein and deoxyribonucleic acid in the Kupffer cells, but in no changes in collagenase activity. An increase in collagen degradation was suggested, however, by the increase in the urinary excretion of hydroxyproline and glycosaminoglycans found after 2 and 6 mth of ethanol feeding, respectively. This study demonstrates that fatty infiltration of the liver in the rat, after prolonged ethanol feeding, is associated with increased deposition of chemically detectable collagen and evidence of increased collagen degradation, although no significant changes in parameters associated with hepatic collagen synthesis were found.