Inter-relação entre a esquistossomose mansoni e a síndrome metabólica no modelo C57BL/6

Abstract

The aim of this study was to investigate the relationship between schistosomiasis mansoni and metabolic syndrome in the experimental model C57BL/6. At two months of age, male mice received a standard diet (10g lipid/100g diet) or high-fat diet (60g lipid/100g diet). After 90 days of initiation of dietary administration, two groups were infected subcutaneously with approximately 80 cercariae of Schistosoma mansoni (BH strain): infected standard diet (ISC, n= 9) and infected hyperlipidemic diet (IHFC, n=10). Uninfected controls were: standard diet (SC, n=5) and high-fat diet (HFC, n=9). In the seventh week of infection, the infected groups were submitted to parasitological examination, and in the following groups, the oral glucose tolerance test was performed. Euthanasia occurred twenty-one weeks after the start of diet administration and with 9 weeks of infection. Blood samples were collected for biochemical analysis (total cholesterol, triglycerides, HDL and LDL), while visceral fat deposits and livers were removed and weighed. Liver samples were submitted to routine histological processing and stained with Hematoxylin and Eosin, Picrosirius and Masson's Trichrome. Stereological analyzes (D36, disector), morphometric (area and perimeter), verification of the cellular composition of periovular granulomas and quantification of inflammatory infiltrate points were performed. The groups were compared by the Kruskall Wallis tests, Dunn's multiple comparisons or analysis of variance ANOVA and Tukey's post test. The values of p≤0.05 were considered significantly different and the data were presented in mean±standard error of the mean (EPM). As expected, the high-fat diet induced dyslipidemia and weight gain in the HFC group, however, the infection caused lower body mass gain and weight of the IHFC group mice. The infected groups had greater hepatic mass than the uninfected ones. HFC presented lower oral tolerance to glucose followed by HFCS. Concentrations of total cholesterol, triglycerides and LDL were significantly lower in IHFC compared to HFC. Stereology showed that SC showed higher hepatocyte volume density (Vv [h]) and higher volume density of sinusoids (Vv [s]) compared to ISC, HFC and IHFC, the higher volume density of hepatic fibrosis Vv [hf] in IHFC compared to ISC (p <0.05). IHFC with higher volumetric density of liver necrosis Vv [n] and lower steatosis volume density (Vv [st]) relative to HFC. The IHFC group showed with more inflammatory infiltration points and numerical density of binucleated hepatocytes N [bh]. The morphometry of granulomas revealed a larger area and perimeter in IHFC compared to ISC. Histopathology confirmed the morphometric and stereological data, indicating the presence of macro and microvesicular steatosis in HFC, and a significant reduction in HFCS. The main histological aspects were necrosis points, inflammatory infiltrate and ballooned hepatocytes, with a simple deposition of collagen fibers in the IHFC group compared to ISC. The results advance the knowledge of the relationship between schistosomiasis and dyslipidemia, when the concomitance between beneficial and deleterious aspects resulting from this comorbidity is demonstrated. There is still much more information needed to truly understand the complex relationships in this comorbidity.