AVALIAÇÃO DO EFEITO DO TRATAMENTO COM Dysphania Ambrosioides (L.) MOSYAKIN & CLEMANTS SOBRE O DESENVOLVIMENTO DE GRANULOMAS DE Schistosoma mansoni EM DIFERENTES FASES DA INFECÇÃO

Abstract

Schistosomiasis is a neglected disease, of great importance for public health in the world, which can be caused by the helminth species Schistosoma mansoni. The treatment of the patient is based on the use of the drug praziquantel. However, this drug has some disadvantages, such as low efficacy in the young stages of the parasite (schistosomula) and inability to reverse inflammatory lesions induced by the formation of granulomas. Therefore, there is a need to develop new therapeutic alternatives to control and prevent severe forms of the disease. In this sense, the objective of this work was to review the use of plant products in the treatment of schistosomiasis and to investigate whether treatment with Dysphania ambrosioides extract induces immunological and histopathological changes in the development of granulomas in the liver, intestine and lung of mice infected and treated in different phases of experimental infection. The results of this thesis are presented in 03 (three) chapters. In chapter 1 we made a narrative review on the immunomodulatory and antiparasitic effects of natural products, originating from plant species, and their major constituents in the treatment of schistosomiasis, carried out based on research found in the PubMed, LILACs and MEDLINE databases in the period 2008 to 2021. It was shown that treatment with extracts from plant species acts directly on the parasite, reducing the chances of survival, which reduces the number of eggs and granulomas in the vertebrate host. Treatment with natural products also reduces the levels of pro-inflammatory cytokines, in addition to activating neutrophils, macrophages, T lymphocytes and B cells, which improves the pathogenesis of the disease, ensuring host survival. In chapter 2 we evaluate the effect of the hydroalcoholic extract of D. ambrosioides (EHDA) on oviposition and infection pathology. To this end, the effect of the D. ambrosioides extract on the mortality and oviposition of adult S. mansoni worms was evaluated in vitro. In order to understand the possible causes of inhibition of parasite oviposition, in silico evaluations were carried out using the majority constituent of the extract, kaempferol, and its biological activities and potential molecular target in the S. mansoni parasite were predicted. Additionally, in vivo treatment evaluations were carried out in each of the development phases of S. mansoni (cutaneous, pulmonary, immature worms and mature worms) using mice, infected with 50 cercariae and euthanized 60 days post-infection. In vitro evaluations, EHDA showed schistosomicidal activity and inhibited the oviposition of female worms. Treatment with EHDA reduced the size and number of granulomas, as well as histopathological lesions in the liver, intestinal and lung tissues, demonstrating a better organization of the granulomatous response. There was a predominance of type I collagen fibers in the tissues of mice treated with EHDA. Chapter 3 consisted of the evaluation of the dynamics of immunological and histomorphometric association in granulomas from mice infected and treated or not with EHDA through in vivo experiments. EHDA reduced blood eosinophils and IgE levels, although without significant association with the area and number of granulomas. Regarding cytokine levels, Th2 and Th17 responses were reduced throughout the development phases of S. mansoni. Notably, there was a negative association between Th1 and Th17 responses with the area and number of hepatic and intestinal granulomas. These results demonstrate that EHDA has therapeutic potential against schistosomiasis, acting in several aspects, from parasite mortality to modulation of the host's immune response. Therefore, they are an important step towards proposing new therapies for schistosomiasis, especially with natural products on the formation of granulomas, which constitute the main pathology of schistosomiasis.