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

Publisher Website
Google Scholar
Abstract
Penicillin is often used to prevent growth of undesirable microorganisms in short- and long-term cell cultures. Rat liver parenchymal cells were isolated from normal and barbiturate-pretreated rats. Cells from untreated animals were exposed to penicillin over a concentration ranging from 0.14-14.0 mM (50-5000 .mu.g/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 of penicillin (1.4 mM) on protein incorporation, enzyme leakage and viability was compared to the effect of paracetamol (6.6 mM) and tert-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. tert-Butanol showed no such effect. No drug affected the viability or leakage of enzymes from the hepatocytes. In cells from barbiturate-treated animals, paracetamol, penicillin and tert-butanol all had a significant inhibitory effect on the incorporation of radioactively labeled precursor into cell and medium protein, but no effect on the leakage of enzymes or viability. The ratio between labeled medium and cell proteins was 31% lower in suspensions of control cells from barbiturate-treated animals than in cells from untreated rats. 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 .mu.g/ml.