Decrease in liver collagen accumulation in carbon tetrachloride-injured and normal growing rats upon administration of zinc.
Several attempts have been made to develop antifibrotic drugs for human use, but their success has been limited. The present data suggest that peroral zinc treatment has a direct and selective inhibitory effect on carbon tetrachloride-induced collagen accumulation in rat liver. Zinc did not normalize the carbon tetrachloride-induced increases in either liver relative weight, liver total protein content, fat accumulation, or the standard liver function tests, but it did efficiently inhibit liver collagen accumulation. It also reduced skin and liver collagen content and urinary hydroxyproline excretion in normal growing animals, indicating that the inhibition is not limited to the fibroproliferative inflammation associated with carbon tetrachloride injury. Neither inhibition of polysomal protein synthesis nor increased degradation of mature collagen fibers was found to play any major role in the effect of zinc. Instead, a plausible mechanism is inhibition of proline hydroxylation.
D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury; D003094:Collagen / Q000378:metabolism*; D005260:Female; D005964:Glucosyltransferases / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism*; D008111:Liver Function Tests; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015032:Zinc / Q000494:pharmacology*
D003094:Collagen; D011393:Procollagen-Proline Dioxygenase; D005964:Glucosyltransferases; C023247:UDP glucose-collagen glucosyltransferase; D015032:Zinc