Ultrastructural analysis of ß-lapachone-induced surface membrane damage in male adult Schistosoma mansoni BH strain worms.

The present study provides, for the first time, conclusions on the in vitro schistosomicidal properties of ß-lap. Adult male Schistosoma mansoni worms of the BH strain were used for the study. Motility, mortality, cell viability and alterations in the tegument were employed as schistosomicidal parameters. Alterations in motility were observed 6h after incubation in concentrations of 50 and 100 µM. ß-lap decreased significantly the worm viability, reducing the formation of formazan in 17.7%, 27.4% and 54.8% at concentrations of 25, 50 and 100 µM, respectively. Mortality in concentrations of 50 and 100 µM was of 67% and 100%, respectively, after 24h. The death of the parasite was preceded by progressive surface membrane damage, characterized by tegument peeling, spine reduction and erosion, blister formation and rupture, and the emergence of holes. In addition to this, in the anterior portion, intense general edema, areas of cracking with a wrinkled surface, furrows and a fibrous appearance were also observed. The results of the present study thus provide a sound basis for further in-depth studies of the schistosomicidal properties of ß-lap, both in the laboratory and in the field.

ß-Lapachone: a naphthoquinone with promising antischistosomal properties in mice.

The activity of ß-lapachone (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione, ß-lap) against different stages of Schistosoma mansoni was investigated in mice. Mice infected with 50 cercariae (BH strain) were intraperitoneally treated at a dose of 50 mg/kg for 5 consecutive days, starting on the 1st, 14th, 28th and 45th days after infection, to evaluate the effect of ß-lap on skin schistosomula, lung schistosomula, young worms (before oviposition) and adult worms (after oviposition), respectively. All animals were euthanized 60 days after infection. ß-Lap significantly reduced (p<0.001) the number of worms in 29.78%, 37.2%, 24.2% and 40.22% when administered during the phases of skin schistosomula, lung schistosomula, young worms and adult worms, respectively. Significant reduction was also achieved in terms of female burden. In all groups, there was significant reduction in the number of eggs and granulomas in the hepatic tissue. When the intervention was performed during the phase of adult worms, ß-lap reduced the size of hepatic granulomas and changed the oogram pattern, lowering the percentage of immature eggs and increasing the percentage of mature and dead eggs. Our data indicate that ß-lap has moderate antischistosomal properties. Its molecule may also be used as a prototype for synthesis of new naphthoquinone derivatives with potential schistosomicidal properties. Further studies with different formulations containing ß-lap are needed to clearly establish the best dose and route of administration and its mechanism of action against schistosomes.