Ultrastructural modifications during the metabolism of metronidazole by Trypanosoma cruzi.

ABSTRACT

Trypanosoma cruzi epimastigotes incubated in the presence of [14C] metronidazole are capable of a rapid uptake of the drug as shown by timecourse experiments and by autoradiography of the cells. The drug is metabolized to a more polar compound which has the chromatographic behavior of 2-methyl-5-nitroimidazole-1-yl-acetic acid. Mass spectral analysis of the metabolite shows diagnostic mass values (185, 184, 126) which are compatible with the 2-methyl-5-nitroimidazole-1-yl-acetic acid derivative. Flavone dramatically increases the production of the metabolite both in control and cells pretreated with phenobarbital. The cells show the presence of vesicles whose number is not significantly increased by phenobarbital. Metronidazole, on the other hand, significantly increases the number of vesicles in both control and cells grown in phenobarbital. The vesicles do not contain acid phosphatase and/or polyphosphates. It is concluded that the vesicles may correspond to a marked proliferation of the endoplasmic reticulum. A secondary effect of flavone is the proliferation of the mitochondrial membranes.