Efectos del nifurtimox, benznidazol y beta-lapachona sobre el metabolismo del ADN, ARN y proteínas en Trypanosoma cruzi / [Effects of nifurtimox, benznidazole, and beta-lapachone on the metabolism of DNA, RNA and proteins in Trypanosoma cruzi]

ABSTRACT

Nifurtimox and benznidazole have trypanostatic actions in vitro and inhibit the incorporation of [3H] thymidine, [3H] uridine and L-[3H] leucine in T. cruzi macromolecules. The effect of nifurtimox may be explained by (a) direct inhibition of nucleic acid biosynthesis, or (b) generation of the oxygen radicals in T. cruzi and therefore, only mechanism (a) should be valid. In order to obtain more information on the action of these drugs on T. cruzi, in the present study we examined the effect of nifurtimox and benznidazole on DNA, RNA and protein turnover in epimastigote (culture) forms of the parasite. Complementary experiments were performed with beta-lapachone that, like nifurtimox, generates oxygen radicals in T. cruzi. Epimastigotes (Tulahuen strain) at the exponential-phase of growth were cultured with [3H] thymidine, [3H] uridine or L-[3H] leucine to label DNA, RNA and protein, respectively. After incubation, the cells were washed free of radioactive precursor, resuspended in fresh medium and reincubated at 30 degrees C with nifurtimox (10 or 100 microM), benznidazole (38 or 380 microM) or beta-lapachone (1.6 or 7.8 microM), for 1-3 hours. Controls were incubated without drug. At one hour time intervals, sampler were taken, washed free of medium and filtered through 0.45 microns Metricel filters. The filters were washed with 10