Uptake of metronidazole and its effect on viability in trichomonads and Entamoeba invadens under anaerobic and aerobic conditions

Abstract

[(14)C]metronidazole used at the chemotherapeutic concentration of 10 mug/ml is taken up rapidly by the anaerobic protozoa Tritrichomonas foetus, Trichomonas vaginalis, and Entamoeba invadens kept under anaerobic conditions. It can be calculated that within 30 to 60 min the intracellular concentration of the label is 50 to 100 times higher than in the medium. The presence of air markedly suppresses the uptake in the trichomonads and abolishes it in E. invadens. The suppression disappears after anaerobic conditions are established. The rate of uptake in T. foetus is dependent on the concentration of the drug in the range studied (1 to 200 mug/ml). Analysis of double reciprocal plots suggests that the drug enters the cells predominantly or exclusively by diffusion. The major factor driving the uptake is most likely the intracellular biotransformation of the compound. If less than 3 mug of drug per mg of protein is taken up by T. foetus no decrease in viability is observed. Above this level the cytotoxic activity corresponds roughly to the amount accumulated in the cell, irrespective of whether the conditions are anaerobic or aerobic.