Estudo da esquistossomose mansônica associada a dislipidemia em modelo experimental: Implicações no fígado, tecido adiposo e nos helmintos após tratamento com praziquantel

Abstract

Schistosomiasis is a neglected disease affecting millions of people in endemic areas, with its progression strongly influenced by the host’s metabolism, and praziquantel (PZQ) being the only available therapeutic option. In this context, the present study aimed to investigate the therapeutic response to PZQ in acute schistosomal infection, assessing remodeling of the liver and visceral adipose tissue, as well as the effects on Schistosoma mansoni recovered from mice subjected to a high-fat diet (HFD). Female mice received either an HFD or a standard diet, and after 24 weeks were infected with 100 S. mansoni cercariae (LE strain). At week 32, animals were treated with a single dose of 60 mg/kg PZQ. At week 34, animals were euthanized, and blood samples were collected for biochemical analyses. Peritoneal macrophage and splenic lymphocyte cultures were performed to evaluate cytokine profiles. Liver and adipose tissue were collected for histopathological, stereological, and morphometric analyses, with a portion of the liver reserved for assessment of hepatic bioenergetics and parasitic load. Worms were recovered from the portal and mesenteric veins, separated by sex, fixed, stained, and analyzed by microscopy. Results showed that the HFD induced metabolic and inflammatory alterations, including dyslipidemia, vascular remodeling, tissue inflammation, and disruption of hepatic architecture, although it also activated compensatory lipid oxidation pathways. S. mansoni infection modulated some of these effects, reducing plasma lipids and certain markers of liver injury, while simultaneously exacerbating metabolic stress, promoting mitochondrial dysfunction, vascular remodeling, and intense inflammation in the liver and adipose tissue, as well as supporting parasite reproduction and adaptation. PZQ treatment in mice fed a standard diet was safe and effective, reducing worm and egg burdens, inducing morphological changes in the parasite tegument, relieving hepatic metabolic stress, and remodeling adipose tissue. However, the HFD modulated the drug response, conferring greater protection to the parasite tegument, decreasing vascular displacement in the liver, and altering host metabolic and immune responses. This modulation resulted in less structural restoration in the liver and adipose tissue in animals on the HFD compared to those on a standard diet. These findings demonstrate that the host’s nutritional status directly influences the therapeutic efficacy of praziquantel, highlighting the importance of the metabolic context in the progression of schistosomiasis.