Penicillin Toxicity in Isolated Rat Hepatocytes Revealed by Decreased Incorporation of Valine into Proteins

: Rat liver parenchymal cells were isolated from normal and barbiturate pretreated rats. Cells from untreated animals were exposed to penicillin over a concentration range from 0.14 mM to 14.0 mM (50–5000 μg/ml). An inhibition of the incorporation of 14C valine into stationary and medium proteins, ranging from 23% at 0.28 mM to 90% at 14.0 mM, was observed. The effect of a single dose penicillin (1.4 mM) on protein incorporation, enzyme leakage and viability was compared to the effect of paracetamol (6.6 mM) and tertiary butanol (10.9 mM). In these concentrations paracetamol and penicillin both inhibited the incorporation of valine into cell and medium protein in hepatocytes from untreated rats. Tertiary butanol showed no such effect. No drug affected the viability or the leakage of enzymes from the hepatocytes. In cells from barbiturate treated animals both paracetamol, penicillin and tertiary butanol had a significant inhibitory effect on the incorporation of radioactive labelled precursor into cell and medium proteins, but no effect on the leakage of enzymes or viability. The ratio between labelled medium and cell proteins was 31% lower in suspensions of control cells from barbiturate treated animals than in cells from untreated rats. It was concluded that penicillin may exert marked effects on protein metabolism in the frequently used isolated rat hepatocyte system, esspecially if the drug concentration well exceeds the usual cell culture concentration of 30–60 μg/ml.