In-vitro toxoplasmacidal activity of cationic electron carriers

Exposing murine macrophages infected with the protozoan parasite Toxoplasma gondii to micromolar concentrations of some cationic electron carriers (dyes), resulted in complete killing of the intracellular parasites at concentrations at which these compounds did not seem toxic for the macrophages. The 50% inhibitory concentrations (with 95% confidence limits) were calculated as 0.26 (0.18-0.37), 1.35 (1-2.25), 0.45 (0.13-1.50), and 1.52 (0.91-2.53) microM for crystal violet, phenazine methosulphate, methylene blue and brilliant cresyl blue, respectively. The effects of these electron carriers did not appear to be the result of an enhancement of the natural antitoxoplasmic activity of the macrophages. None of the tested compounds was active against extracellular Tox. gondii as measured by ability to reinfect murine macrophages; thus, these dyes seem to act primarily on actively metabolizing, intracellular, Tox. gondii. Our data also suggest that the killing effect of the electron carriers was not related to the generation of reactive oxygen intermediates as judged by the inability of scavengers of these intermediates to block the activity against intracellular Tox. gondii. Further studies with related redox compounds would have an interesting chemotherapeutic perspective for treating toxoplasma infections.