Biphasic effect of colchicine on acute liver injury induced by carbon tetrachloride or by dimethylnitrosamine in mice

Background/Aims: The effects of colchicine on acute liver injury induced by carbon tetrachloride or by dimethylnitrosamine in mice were examined. Methods: Nonlethal acute liver injury was induced in male BALB/c mice by a single intraperitoneal injection of 0.8 ml/kg carbon tetrachloride or 15 mg /kg dimethylnitrosamine. 0.6 mg/kg colchicine was administered 18 h or 2 h intraperitoneally before hepatotoxin treatment. Results: Reversible centrilobular to mid-zone necrosis and apoptosis occupy ing half the liver lobular area was evoked by carbon tetrachloride, and dim ethylnitrosamine, respectively. Administration of colchicine 18 h before he patotoxins markedly suppressed liver injury whereas colchicine administrati on 2 h before the hepatotoxins accelerated it. The hepatoprotective effect evoked by colchicine was due to reduction in liver cytochrome P450 content and P450 2E1 activity, In contrast, the hepatodestructive effect seen in th e carbon tetrachloride model was related to the extent of lipid peroxidatio n promoting plasma membrane destruction, while the hepatodestructive effect in the dimethylnitrosamine model was due to suppression of Bcl-x(L) expres sion, leading to acceleration of apoptosis. Conclusions: A biphasic effect of colchicine on carbon tetrachloride- and d imethylnitrosamine-induced acute liver injury was seen, The time interval b etween colchicine administration and the hepatotoxin treatment is crucial t o the subsequent development of liver lesions.