Avaliação do efeito dos tratamentos com Praziquantel e Dapsona no remodelamento da matriz extracelular hepática em modelo experimental de esquistossomose

Abstract

Introduction: Chronic schistosomiasis is characterized by the formation of perivascular granulomas, which alter the structure of the hepatic extracellular matrix (ECM), especially in cases of successive reinfections. Praziquantel (PZQ), although effective in eliminating S. mansoni, does not act directly on ECM remodeling, does not prevent reinfections, and is not effective in all stages of the parasite’s life cycle. This highlights the need for a drug that directly targets the chronic effects on ECM caused by the disease. Previous studies from our group indicated that exposure of endothelial cells to S. mansoni induces the expression of catalase, an antioxidant enzyme that reduces oxidative stress and may favor parasite survival. Based on this, we became interested in evaluating dapsone, a drug known to selectively inhibit catalase, as a potential adjuvant therapy to modulate the inflammatory response and tissue remodeling in chronic schistosomiasis. Objective: To evaluate the influence of treatments with PZQ and dapsone on extracellular matrix remodeling in a murine model of S. mansoni infection, focusing on the composition and organization of the ECM in the hepatic microenvironment. Methodology: Fifty Swiss mice were infected with 75 S. mansoni cercariae and, after seven weeks, were treated by gavage with Praziquantel and dapsone for 15 days. At the end of the experiment, perfusion of the mesenteric vein was performed to assess parasite burden, and liver tissue was collected for ECM analysis. Histological staining techniques (Picrosirius Red and Masson's Trichrome), cell counting, and immunohistochemistry were used to quantify versican, collagen types I and III, and catalase. The data was subsequently analyzed using ImageJ software. Results: Mice treated with dapsone showed a lower number of granulomas, as well as a reduction in ECM area, versican, and collagen types I, III, and total. Despite this reduction, there was an increase in catalase expression, suggesting a compensatory mechanism to oxidative stress. Mice treated with PZQ showed greater ECM deposition, indicating an active healing process associated with parasite death. The combination of PZQ and dapsone appeared to intensify granuloma formation and increase mononuclear cell infiltration, which may be related to an exacerbated immune response. Conclusion: The combined therapy of PZQ and dapsone did not significantly reduce ECM remodeling, but treatment with dapsone alone showed potential in inhibiting granuloma development in mice infected with S. mansoni. These findings indicate that dapsone may modulate the inflammatory response and matrix remodeling in chronic schistosomiasis.