Estudo das alterações histopatológicas e inflamatórias hepáticas após dieta regional básica em camundongos C57BL6J

Abstract

Malnutrition is still considered endemic in many developing countries, especially in sub-Saharan Africa and some Asian countries. In Brazil, the prevalence of malnutrition has declined; however, the malnutrition-enteric infection complex may cause long-term effects, including growth and cognitive deficits, especially in children living in poor areas without sanitation. The regional basic diet (RBD), produced to mimic the Brazilian Northeastern dietary characteristics (enriched in carbohydrate and with low protein), has been used in several experimental models of malnutrition, but few studies have explored the effect of the chronic RBD treatment on the liver, a central organ involved in the cholesterol metabolism and the immunoinflammatory responses. This study aimed to investigate liver histopathological and inflammatory changes and the reverse cholesterol metabolism of C57BL6/J mice treated with the RBD (undernourished group) for 40 days post-weaning, compared to the nourished control group, receiving a standard chow diet. Animals were weighed daily. After 40 days, blood was drawn to determine the alanine aminotransferase (ALT) serum levels, a marker of liver function, and to assess liver histopathology (histological score) and inflammation (TNF-α and IL-10 by q- PCR). In addition, we analyzed the ionized adapter calcium protein-1 (IBA-1) immunohistochemistry, a marker for Kupffer cells, and IL-1β. Furthermore, we assessed the reverse cholesterol metabolism (apoE, apoA-1 and LCAT). The RBD induced a decrease in body weight gain compared with the nourished group (p<0.05). There was no statistical difference in serum ALT in the experimental groups. In histological sections, we identified greater IBA-1 immunolabeling and a significant increase in the number of positive-IBA-1 cells in the undernourished group when compared to the control group. Regarding liver cytokine analyses, greater TNF-α (p<0.0001) and IL-10 (p=0.001) mRNA expression was found in RBD-challenged mice. Regarding the revere cholesterol transport, we found significantly increase in apoA mRNA expression in the undernourished group (p=0.04), but not APOE and LCAT, compared with the control. Altogether our findings suggest that chronic RBD-induced malnutrition leads to an inflammatory condition of the liver, indicated by a stronger IL-1β immunolabeling and increased number of IBA-1 labeled liver cells, as well as, increased expression of TNF-α and IL-10