FIBROGENIC AND COLLAGENOLYTIC ACTIVITY IN CARBON-TETRACHLORIDE-INJURED RATS - BENEFICIAL-EFFECTS OF ZINC ADMINISTRATION

Collagen synthesis and degradation in normal and carbon-tetrachloride- injured male Wistar rats at early and late stages of liver fibrosis, a nd the potential beneficial effects of zinc supplementation on liver f ibrogenesis and collagenolysis have been assessed by measuring hepatic collagen content and prolyl hydroxylase and collagenase activities. N o significant changes in hepatic collagen and prolyl hydroxylase activ ities were observed between control rats (82+/-25 cpm/mg protein) and rats with induced cirrhosis (107+/-23 cpm/mg protein) after 4 weeks of carbon tetrachloride injury. By this time, hepatic collagenase activi ty was significantly lower in rats with induced cirrhosis (61+/-9 mu u /mg protein) than in control rats (133+/-31 mu u/mg protein) (p<0.05). This result was prevented by zinc administration, since hepatic colla genase activity was similar in zinc-supplemented, carbon-tetrachloride -injured rats and normal rats (148+/-19 mu u/mg protein). After 16 wee ks, all carbon-tetrachloride-injured rats had cirrhosis. Hepatic colla gen content and prolyl hydroxylase activity were significantly higher in carbon-tetrachloride-injured rats than in controls. These effects w ere partially prevented by zinc administration, since only two of the seven zinc-supplemented, carbon-tetrachloride-injured rats had cirrhos is. Moreover, prolyl hydroxylase activity was significantly lower in z inc-supplemented injured rats (263+/-27 cpm/mg protein) than in the no n-supplemented respective controls (389+/-52 cpm/mg protein) (p<0.05). No significant changes in hepatic collagenase activity were observed at this stage of liver injury. We conclude that zinc supplements influ ence hepatic fibrosis by decreasing the elevated fibrogenic activity i n late stages of liver injury, and increasing hepatic collagenolysis w hich is suppressed in early stages of liver fibrosis. (C) Journal of H epatology.