Prevention by zinc of rat lung collagen accumulation in carbon tetrachloride injury.

Orally administered zinc was studied as a protective antifibrotic agent with respect to experimentally caused lung collagen accumulation in rats. Intraperitoneally injected carbon tetrachloride induced a diffuse alveolar damage with interstitial pulmonary fibrosis, and the morphologic findings suggested a primary toxic effect on the lungs. The carbon tetrachloride induction increased significantly the lung to body weight ratio, lung total protein and collagen content, lung total prolyl hydroxylase and galactosylhydroxylysyl glucosyltransferase activities, and daily urinary hydroxyproline excretion. Treatment with 114 mg/L of zinc in the animals' drinking water inhibited the lung prolyl hydroxylase activity and prevented the increases in lung collagen content and urinary hydroxyproline excretion but did not normalize any of the other above parameters. Enhanced lung prolyl hydroxylase activity was noted when a ferrous ion excess was included in the assay in order to reverse the competitive inhibition of the enzyme activity by zinc. It is suggested that zinc has a direct and selective preventive effect on rat lung collagen accumulation by inhibiting procollagen proline hydroxylation.