Inibição do Sistema Antioxidante Parasitário como Alvo contra Esquistossomose mansônica

The WHO estimates that 200 millions of people are with Schistosoma sp. in the world, where less than 10% of this population receive appropriate treatment. In Brazil, the mansoni schistomiasis is endemic in vast area most states, the confirmed cases number augmented more than 100-fold between 1995 and 2010 according the Ministry of Health. Among the brazilian states, Bahia is the one with the greatest endemic area. Currently, the treatment is performed with praziquantel and oxamniquine, however there is reports efficacy reduced and resistance to these drugs. That increased the need for new drugs and therapeutic regimens to prevent the selection of resistant strains. A way into this quest is the combination of substances, thus use of quinoline drugs that stop heme detoxification, associated to inhibitors of antioxidant system of parasite, it’s may increases of deleterious effects of this metabolite. So, aiming to assess in vitro chloroquine effect (CLQ – inhibitor of heme aggregation) against to adult worms of Schistosoma mansoni, and sodium diethyldithiocarbamate (DDC - superoxide dismutase inhibitor), thus isolated as combined. The cytotoxicity was assess of MTT reduction in splenocytes cell culture, while the schistosomicide activity was define for survival of worms in presence of substances isolated and associated. The structure damages of parasite were evaluated by electronic microscopy, as mechanism of action were explored by inhibition of heme crystals formation, as well as increase oxidative stress via liperoxidation analysis and SOD activity. This way, not found significant toxicity by CLQ and DDC in splenocyte and effective dose lethal to 50% of worms (ED50) was 24.3μM to CLQ and 63.1μM DDC. The combination of drugs was more effective at ratio of 4 units of CLQ to 1 of DDC, and ultrastructure evaluation undergoing this treatment showed lost parasite tegument, as the composition of digestive tract. Biochemical investigations carried out have shown this proportion increases liperoxidation and inhibits hemozoin formation drastically. This data indicate a new therapeutic possibility to schistosomiasis that will help to fight with the economic and social impact of this disease.