EFFECT OF THE PROSTAGLANDIN-E1 ANALOG MISOPROSTOL ON THE CARBON TETRACHLORIDE-INDUCED INJURY OF RAT-LIVER CELLS IN CULTURE

Previous investigators have reported a protective effect of some prostaglandins and of the prostaglandin E2 analogue enprostil on carbon tetrachloride (CCl4)-induced injury of liver cells. In the present study liver cells were isolated from the rat liver by collagenase perfusion and suspended in F-10 medium, containing 20% foetal bovine serum, 1% gentamicin, and 1% glutamine. In the first study cells were cultured in T-flasks with 3 ml suspension of 6 x 10(6) cells/ml, and in the second study (extended dose response) cells were cultured in tissue culture wells with 0.5 ml cell suspension. Misoprostol was added to groups of cultures 15 min before CCl4, 2-mu-l/ml, and the number of living cells was counted 45 min after the first addition. The number of living cells was compared with those of other groups with CCl4 only and control groups. In the first experiment misoprostol was given in doses of 200, 400, and 800 ng/ml medium and in the second experiment in 0.1, 1, 10, 100, and 1000 ng/ml medium. CCl4 is an agent well known to be toxic to liver cells, and in cultures to which only CCl4 was added, the number of living cells was significantly reduced compared with controls. When 0.1 ng misoprostol was added before CCl4, no significant difference in the number of living cells was shown compared with cultures with CCl4 only. On the other hand, misoprostol given in doses from 1 ng to 1000 ng before CCl4 resulted in a higher number of living cells, indicating a protective effect.