Studies on the effect of 3,4-dehydroproline on collagen metabolism in carbon tetrachloride-induced hepatic fibrosis

Hepatic fibrosis in rats was induced by chronic subcutaneous treatment with carbon tetrachloride. The amount of collagen and the specific activity of prolyl hydroxylase were greatly enhanced. On treatment of these fibrotic animals with dl-3,4-dehydroproline (100 mg/kg) for 5 consecutive days, the specific activity of liver prolyl hydroxylase was greatly decreased and approached the activity observed in the liver of normal rats. Although carbon tetrachloride did not affect prolyl hydroxylase activity of the lung, administration of dehydroproline caused a significant decrease in enzyme activity. Collagen extracted from normal and fibrotic rat livers was analyzed by chromatography on carboxymethylcellulose. Normal rat liver contains α₁ and α₂ chains with Chromatographic properties similar to Type I collagen of calf skin. Fibrotic liver contains Type I collagen as well as collagen with Chromatographic properties similar to Type III. The increase in the latter type of collagen is more pronounced in the liver of fibrotic animals.