Caracterização in vitro dos efeitos genotóxicos e citotóxicos da droga antimalárica artesunato em linfócitos humanos

Abstract

Malaria is one of the most serious infectious disease in the world, with quite extensive geographic distribution in tropical areas. Its treatment is based on administration of specific drugs, as artemisinin and its derivatives: artesunate, which will be the subject of this study, and artemether. The artesunate is a semi-synthetic compound derived from artemisinin, a substance extracted from the Chinese plant Artemisia annua L. Despite the widespread use of artesunate in antimalarial therapy and the strong evidences that other antimalarials such as partenin and chloroquine present genotoxic effects in vitro; there are few studies that demonstrate artesunate genotoxic effects in human lymphocytes. In previous studies carried out in laboratory human cytogenetics, it was shown that artesunate induces cytotoxic and genotoxic effects in human lymphocytes in vitro. Despite these findings, the mechanisms of these effects have not been adequately characterized due to limitations of the techniques used. This study aimed to assess in vitro the cytotoxic and genotoxic effects of artesunate on human peripheral blood lymphocytes using assays such as FISHMN, oxidative stress and immunocytochemistry by immunofluorescence. We aimed through these tools elucidate the mechanisms responsible for the effects of artesunate in DNA of human lymphocytes. The results found in this study suggest that the artesunate induces the formation of ROS and other free radicals and that these substances are causing DNA damage in human lymphocytes in culture. Thus cells with damaged DNA, not being able to reverse this condition, activate apoptosis through the extrinsic and intrinsic pathways.