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Effect of pheno barbital and di ethyl maleate on carbon tetra chloride toxicity in isolated rat hepatocytes

, : Effect of pheno barbital and di ethyl maleate on carbon tetra chloride toxicity in isolated rat hepatocytes. Experimental and Molecular Pathology 28(1): 48-57

The effects of phenobarbital and the glutathione depleting agent, diethyl maleate, on CCl4 hepatotoxicity were investigated in isolated rat hepatocytes. Administration of diethyl maleate significantly decreased hepatocyte glutathione levels in vivo and in vitro. Addition of CCl4 (400 and 800 .mu.g/ml) to hepatocyte suspensions resulted in increased malondialdehyde formation in cells isolated from diethyl maleate- or diethyl maleate plus phenobarbital-treated rats. Both concentrations of CCl4 increased lactate dehydrogenase release in cells isolated from diethyl maleate plus phenobarbital-treated rats; 800 .mu.g/ml, but not 400 .mu.g/ml, of CCl4 caused moderate lactate dehydrogenase release in cells isolated from diethyl maleate-treated rats. Treatment with phenobarbital alone resulted in increased lactate dehydrogenase release in hepatocytes exposed to 800 .mu.g/ml of CCl4; no significant effects were observed at the 400 .mu.g/ml level. Hepatocytes isolated from rats treated with phenobarbital only did not exhibit significant malondialdehyde formation at either 400 or 800 .mu.g/ml of CCl4. Addition of 800 .mu.g/ml of CCl4 to hepatocytes isolated from phenobarbital-treated rats produced maximal lactate dehydrogenase release which was not further increased by treatment with diethyl maleate. An increased rate of CCl4 bioactivation produces a more prominent effect on lactate dehydrogenase release than on malondialdehyde formation; lowered reduced glutathione levels were associated with increased malondialdehyde formation.


PMID: 620759

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