Antioxidant properties of colchicine in acute carbon tetrachloride inducedrat liver injury and its role in the resolution of established cirrhosis

Antioxidant and antifibrotic properties of colchicine were investigated in the carbon tetrachloride (CCl4) rat model. (1) The protective effect of col chicine pretreatment on CCl4 induced oxidant stress was examined in rats su bsequently receiving a single lethal dose of CCl4. Urinary 8-isoprostane, k idney and liver malondialdehyde and kidney glutathione levels increased fol lowing CCl4 treatment, but only the rise in kidney malondialdehyde was sign ificantly inhibited by colchicine pretreatment. Serum total antioxidant lev els were significantly higher in the colchicine pretreatment group. (2) The long term effects of colchicine treatment on CCl4 induced liver damage wer e investigated using liver histology and biochemical markers (hydroxyprolin e and type III procollagen peptide). Go-administration of colchicine with s ub-lethal doses of CCl4 over 10 weeks did not prevent progression to cirrho sis. However, rats made cirrhotic with repeated CCl4 challenge and subseque ntly treated with colchicine for 12 months, all showed histological regress ion of cirrhosis. (3) The antioxidant effect of colchicine in vitro was evi dent only at very high concentrations compared to other plasma antioxidants . In summary, colchicine has only weak antioxidant properties, but does aff ord some protection against oxidative stress; more importantly, long term t reatment with this drug may be of value in producing regression of establis hed cirrhosis. (C) 2000 Elsevier Science B.V. All rights reserved.