EFFECT OF ALLOPURINOL ON TRYPANOSOMA-CRUZI - METABOLISM AND BIOLOGICAL-ACTIVITY IN INTRACELLULAR AND BLOOD-STREAM FORMS

Allopurinol (4-hydroxypyrazolo [3,4-d]pyrimidine) is an effective agent in vitro against T. cruzi. The important forms of this parasite, with respect to the pathogenesis of Chagas disease in man, are the bloodstream (trypomastigote and the intracellular forms. Experiments with radiolabeled allopurinol and analysis of the metabolic products of this compound by high-performance liquid chromatography showed that both bloodstream and the intracellular forms of T. cruzi metabolize allopurinol in the same manner as was shown for the epimastigotes in vitro. The metabolic pathways for pyrazolopyrimidines in the pathogenic forms were demonstrated with organisms isolated from infected animals and a tissue culture system infected with T. cruzi. Treatment of infected tissue culture with allopurinol eradicated the infection. This investigation implies that allopurinol may be useful in chemotherapy of T. cruzi infections, a supposition which was borne out in 1 animal study.