Associação da esquistossomose mansônica e diabetes mellitus tipo 1 em modelo murino experimental: novas perspectivas sobre o impacto no parasito e no tecido hepático

Abstract

This study aims to understand the association between infection by the helminth Schistosoma mansoni and type 1 diabetes mellitus induced by streptozotocin (STZ) by studying the changes in the helminths and liver. For this purpose, male Swiss Webster mice, 9 weeks old, were divided into 4 groups (n per group = 10). To induce diabetes mellitus, 20 of these animals received 100 mg/kg of STZ intraperitoneally and 10 days after application, animals with blood glucose > 200 mg/dL were considered diabetic. After 30 days, the animals (n = 20) were infected with S. mansoni subcutaneously (± 80 cercariae per animal). The following study groups were then obtained: Group CS - uninfected and non-diabetic animals; Group I - animals infected with S. mansoni; Group D, diabetic animals; and Group DI, diabetic animals infected with S. mansoni. Euthanasia occurred in the ninth week of infection, when the liver was removed and submitted to routine histological processing. Histological sections obtained were stained with H&E, Masson's Trichrome and Picrosirius Red, and analyzed by histopathology, quantitative methods (D36, cell and collagen quantification) and morphometry of granulomas. Adult helminths were removed from the portal system and mesentery veins, separated by sex, fixed in AFA and stained with Hydrochloric Carmine, for evaluation of the structures of the reproductive system, digestive system and tegument in both sexes, by bright field microscopy, SEM and Confocal. When analyzing the male helminths in the DI Group, we noticed a thicker tegument than the specimens in the infected Group (+43%; p=0.001), testicular lobes with changes in their morphology, and empty spaces between the cells. In females, the ovary presented a larger area than in Group I (+21%; p=0.0150), with oocytes that presented variation in cell size, pleomorphism (triangular and rectangular shapes) and empty spaces between them. The histopathological analysis of the liver demonstrated extensive areas of necrosis, several granulomas in confluence, denaturation of endonucleases in the nucleus of hepatocytes (also seen in Group D), cells with hydropic degeneration, hepatic microsteatosis and finally, hyperemia in the vessels and capillaries. Stereology showed a decline in the volume of DI hepatocytes (-15%; p=0.008) and Kupffer cells (-40%; p=0.026), and an increase in cellular infiltrate (+200%; p=0.0151) compared to the CS, I and D Groups, respectively. Evaluating liver regeneration, a significant decrease in mononucleated and binucleated hepatocytes was noted in Group DI compared to Groups D and I. No differences were found in the area and perimeter measurements of the granulomas, however, collagen production was 76% higher in Group DI compared to Group I (p = 0.0159). It was concluded in this study that the association of type 1 diabetes mellitus modified some parameters of schistosomal infection, among them: the thickness of the tegument of male helminths; the reproductive system of males and females; intensified the desorganizational in the liver tissue that occurs in schistosomiasis; and increased collagen deposition in schistosomal granulomas.