Effect of the Prostaglandin E₁ Analogue Misoprostol on the Carbon Tetrachloride-Induced Injury of Rat Liver Cells in Culture

Abstract

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, l%gentamicin, and 1% glutamine. In the first study cells were cultured in T-flasks with 3 ml suspension of 6 × 10⁶ 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 CC1₄, 2 μl/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 CC1₄ 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. CC1₄ is an agent well known to be toxic to liver cells, and in cultures to which only CC1₄ was added, the number of living cells was significantly reduced compared with controls. When 0.1 ng misoprostol was added before CC1₄, no significant difference in the number of living cells was shown compared with cultures with CC1₄ only. On the other hand, misoprostol given in doses from 1 ng to 1000 ng before CC1₄ resulted in a higher number of living cells, indicating a protective effect.

Key Words:

• Carbon tetrachloride
• culture of liver cells
• liver cells
• prostaglandin E₁ analogue