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, and the potential beneficial effects of zinc supplementation on liver fibrogenesis and collagenolysis have been assessed by measuring hepatic collagen content and prolyl hydroxylase and collagenase activities. No significant changes in hepatic collagen and prolyl hydroxylase activities 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 activity was significantly lower in rats with induced cirrhosis (61 +/- 9 micro units/mg protein) than in control rats (133 +/- 31 micro units/mg protein) (p < 0.05). This result was prevented by zinc administration, since hepatic collagenase activity was similar in zinc-supplemented, carbon-tetrachloride-injured rats and normal rats (148 +/- 19 micromicrons/mg protein). After 16 weeks, all carbon-tetrachloride-injured rats had cirrhosis. Hepatic collagen content and prolyl hydroxylase activity were significantly higher in carbon-tetrachloride-injured rats than in controls. These effects were partially prevented by zinc administration, since only two of the seven zinc-supplemented, carbon-tetrachloride-injured rats had cirrhosis. Moreover, prolyl hydroxylase activity was significantly lower in zinc-supplemented injured rats (263 +/- 27 cpm/mg protein) than in the non-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Liver and Alcohol Units, Hospital Clínic i Provincial, University of Barcelona, Spain.
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Deulofeu
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D000818:Animals; D002251:Carbon Tetrachloride; D003094:Collagen / Q000032:analysis / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism / Q000502:physiology; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc / Q000627:therapeutic use*
D003094:Collagen; D002251:Carbon Tetrachloride; D011393:Procollagen-Proline Dioxygenase; C030606:proline, 2-oxoglutarate 3-dioxygenase; D017364:Collagenases; D015032:Zinc