INHIBITION OF TRYPANOSOMA-CRUZI TRYPANOTHIONE REDUCTASE BY CRYSTAL VIOLET

A trypanothione reductase activity is present in all the main differen tiation stages of Trypanosoma cruzi, amastigotes having the highest ac tivity, and trypomastigotes the lowest. Trypanothione reductase could not be induced in epimastigotes exposed to H2O2. The trypanocidal drug crystal violet was a potent inhibitor of T. cruzei trypanothione redu ctase in vitro. The inhibition was competitive with respect to trypano thione with a K-i of 5.3 +/- 0.5 mu M, uncompetitive with NADPH, and i ncreased below pH 7.0 and above pH 8.0. Crystal violet, however, was n ot able to decrease the level of total reduced thiols in intact cells. Dihydrotrypanothione but not reduced glutathione, protected the enzym e from inhibition by crystal violet.