Cytotoxicity of Phenothiazines on Chang Liver Cells as Measured by Enzyme Leakage

Summary

Suspensions of cultured human fetal liver cells were exposed to promazine (PZ) or chlorpromazine (CPZ) at concentrations ranging from 10^-3 to 10^-5 M for periods of 5–60 min. Identical preparations without drugs served as controls. The levels of three enzymes: lactate dehydrogenase, malate dehydrogenase and asparatate amino-transferase were measured in the surrounding media. The differences between the controls and drug preparations were considered to be the result of cytotoxic effect of the drugs. The CPZ appeared more potent in its cytotoxic activity than did PZ, as demonstrated by the effectiveness at lower concentrations and the greater rapidity and amount of enzymes released from the cells at equal concentrations. The results obtained may have a bearing on the known differences in the development of apparent hepatotoxicity in humans who receive the two phenothiazines.