Effects of Prostaglandins on Ethanol Damage in Primary Cultured Rat Hepatocytes

OBJECTIVES: Several reports demonstrated that ethanol administration impairs the DNA synthesis in rat hepatocytes. Also, It has been demonstrated that prostaglandin (PG) helps prevent membrane damage by hepatotoxic chemicals, in this study, the authors examined PG’s effects on the toxicity of ethanol in the primary culture of rat regenerations. METHODS: We examined two kinds of parameters, i.e., DNA synthesis and lipid peroxidation in the primary culture of rat hepatocytes. Hepatocytes were isolated by the collagenase perfusion method. The rate of DNA synthesis was determined by pulse-labelling cultured cells with [(3)H]-thymidine. Incorporation of [(3)H]-thymidine was determined by liquid scintillation spectrophotometer. DNA content was measured by the fluorescence spectrophotometer. The lipid peroxidation was assayed with spectrophotometer. RESULTS: The results were as follows: 1) PG family (PGA(1), PGD(2), PGE(1), PGE(2), PGG(2a), PGI(2) & Thromboxane B(2)) stimulated the DNA synthesis of hepatocytes (especially PGD(2) and PGE(1)), 2) ethanol decreased DNA synthesis by clear dose-dependent manner, 3) the combined treatment of PGD(2) or PGE(1), prevents the decreasing of DNA synthesis, which was induced by ethanol, 4) in ethanol treatment, lipid peroxidation was decreased significantly, but PGD(2), PGE(1) and PGA(1) were not affected, and 5) PGD(2), PGE(1) and PGA(1) decreased lipid peroxidation with ethanol, significantly. CONCLUSIONS: From these results, we concluded that PG could be useful for the treatment of degenerative liver disease and alcohol-induced liver disease in the assumption that further studies on the action mechanims of PG will continue.