A. Gimenez et al., FIBROGENIC AND COLLAGENOLYTIC ACTIVITY IN CARBON-TETRACHLORIDE-INJURED RATS - BENEFICIAL-EFFECTS OF ZINC ADMINISTRATION, Journal of hepatology, 21(3), 1994, pp. 292-298
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.