Effect of β-lapachone on superoxide anion and hydrogen peroxide production in Trypanosoma cruzi

Abstract

Addition of .beta.-lapachone, an o-naphthoquinone endowed with trypanocidal properties to respiring T. cruzi epimastigotes induced the release of O2- and H2O2 from the whole cells to the suspending medium. The same .beta.-lapachone concentration (4 .mu.M) that released H2O2 at maximal rate completely inhibited T. cruzi growth in a liquid medium. The position isomer, .alpha.-lapachone, did not stimulate O2- and H2O2 release, and did not inhibit epimastigote growth. .beta.-Lapachone stimulated H2O2 production by the epimastigote homogenate in the presence of NADH as reductant. The same effect was observed with the mitochondrial fraction supplemented with NADH, where .beta.-lapachone enhanced the generation of O2- and H2O2 4.5- and 2.5-fold respectively. .beta.-Lapachone also increased O2- and H2O2 production (2.5 and 2-fold respectively) by the microsomal fraction with NADPH as reductant. Cyanide-insensitive NADH and NADPH oxidation by mitochondrial and microsomal fractions (quinone reductase activity) was stimulated to about the same extent by .beta.-lapachone. .alpha.-Lapachone was unable to increase O2- and H2O2 production and quinone reductase activity of the mitochondrial and microsomal fractions.