Soluções de reidratação oral no modelo de desnutrição e diarreia induzida pela toxina do cólera em camundongos : corregulação gênica e expressão das proteínas transportadoras SGTL-1, PEPT-1, CAT-1 e SN2

Abstract

The morbidity and mortality rates rise when diarrhea is associated with malnutrition. However, the mechanisms by which nutritional deficiencies affect the gut are largely unknown. The aim of this study was to evaluate morphological changes in transport proteins and substrates in intestinal transport of electrolytes and water in malnutrition model in mice. We aim to further analyze the effect of cholera toxin (CT) with or without malnutrition on the carrier proteins substrates on electrolyte transport in mice and finally, we evaluate the effects of oral rehydration solutions (ORS) of OMS (SGli) e modified with glutamine (SGln), alanyl-glutamine (SAla-Gln) and arginine (SArg) in this transport. Mice (n=20) received for 7 days a diet deficient in protein, fat and minerals (DBR). Segments of ileum were obtained before and on day 7 of the diet, for studies of morphology, immunohistochemistry for proteins: SGTL-1, PEPT-1, CAT-1 and SN-2 and evaluated by RT-qPCR of mRNA expression of these transport proteins. The model of intestinal perfusion for 75 min in mice (n=6) was used to evaluate the intestinal transport of water and electrolytes and to evaluate the role of oral rehydration solutions in mice exposed nourished and malnourished or without cholera toxin (1µg/ml). Malnourished animals showed weight loss, atrophy of the villi and reduced expression by immunofluorescence of SGTL-1. Malnutrition also caused a reduction in mRNA expression SGTL-1 and PEPT-1 and increased mRNA expression for SN-2 in mice ileum. In the model of intestinal perfusion, acute malnutrition increased intestinal secretion of electrolytes and water. CT increased the secretion of electrolytes and water into the intestinal perfusion model mice. SGli, SGln, SAla-Gln and SArg decreased secretion of electrolytes induced by CT. Just SGln failed to significantly decrease water secretion induced by CT. CT increased mRNA transcription for intestinal transporters SGTL-1, PEPT-1 and CAT-1 but not to increased transcription SN -2. Only SGli reduced water secretion induced by CT. SGli, SAla-Gln and SArg, but not SGln , decreased secretion of sodium and chloride induced by CT. The malnutrition associated with diarrhea caused by TC reduction in the transcription of mRNA for intestinal transporters SGT -1, PEPT-1, CAT-1 and SN-2. Malnutrition associated with CT increased the secretion of water when compared to the group fed exposed to TC. SGli , SAla-Gln and SArg, but not SGln, decreased water secretion induced by malnutrition associated with TC. All solutions decreased secretion of sodium and chlorid induced malnutrition associated with TC.