Loss of calcium regulation across the plasma membrane of hepatocytes is responsible for irreversible cell damage by CCI,. The mode of action of colchicine in CCI, acute liver damage is not completely understood. We followed the time courses of the changes in lipoperoxidation, the activities of liver plasma membrane Ca2+-ATPase, y-glutamyl transpeptidase and alkaline phosphatase, as well as the time courses of serum markers of liver damage in rats acutely intoxicated with CCI4. We assessed the effects of colchicine in this model and evaluated the effect of this drug on liver cytochrome P-450. Increased lipoperoxidation is the earliest and shortest lasting effect of CCI4 in the liver and is followed by a decrease in the activities of plasma membranebound enzymes. The alterations in serum enzymes showed a slower onset and were more protracted. Colchicine pretreatment produced a small decrease in cytochrome P-450 in the liver but completely prevented most of the changes produced by CCI, in lipoperoxidation, liver plasma membrane enzyme activities and serum enzyme activities. We conclude that CCI4 metabolites trigger lipoperoxidation and then produce a longer lasting change in the plasma membrane, which thus allows calcium accumulation. Colchicine prevents the early mechanisms of CCI4 damage, and its effect on cytochrome P-450 perhaps plays only a contributory role.
Methods
Male Wistar rats weighing 200-250 g and fed Purina Chow diet ad libitum were used in these experiments. Animals were divided into four groups: group 1 02h(~37)