Efeitos dos fruto-oligossacarídeos (FOS) no prétratamento e tratamento sobre a mucosite intestinal, induzida por 5-fluorouracil, em modelo experimental

Abstract

Literature data have shown beneficial effects of the use of prebiotic fructooligosaccharides (FOS) in intestinal diseases, as an anti-inflammatory activity, intestinal microbiota modulation and increase in the production of short chain fatty acids (SCFA). The goal of the present study was to evaluate the effects of FOS pretreatment and treatment on intestinal mucositis induced by 5-fluorouracil (5-FU) and investigate possible mechanisms involved in the action of this prebiotic. For this purpose, Balb / c mice, 6 weeks old, weighing between 25 and 30 g were divided into 5 groups: Control (without mucositis + saline), FOS (without mucositis + 6 % FOS), MUC (mucositis + saline solution), PT (mucositis + supplementation with 6 % of FOS before of disease induction) and T (mucositis + supplementation with 6 % of FOS after disease induction). The animals (n = 6) were fed with a commercial diet and supplemented by gavage. Mucositis was induced with a single intraperitoneal injection (300 mg / kg) of 5-FU. After 72 hours of the injection, mice received 18.5 MBq of 99mTc-DTPA by gavage for evaluation of intestinal permeability (PI); 4 hours after administration the animals were euthanized and blood was collected for radioactivity counting. The ileum was also removed for evaluation of inflammatory infiltrate, oxidative stress and histological analysis. Feces were collected for SCFA analysis. The data showed that before of mucositis induction no modifications were observed for feed intake and weight variation to different groups investigated. However, after induction of the disease, there was a reduction of both parameters to MUC group and FOS supplementation was not able to prevent the reduction observed for consumption and weight loss. Animals that received FOS showed physiological levels of intestinal permeability (PI). MPO and EPO activities were increased in the MUC group in relation to the other groups (p0.05); the same did not occur in relation to NAG (p0.05). Regarding to oxidative stress, a reduction of the SOD enzyme activity was observed in the animals of the MUC, PT and T groups in relation to the CTL (p0.05). On the other hand, an increase of the catalase enzyme was observed in the animals that were supplemented with FOS in relation to the MUC group (p0.05).Histological data showed partial preservation of intestinal architecture in the ileum of animals supplemented with FOS. Pretreatment with FOS increased levels of SCFA acetate and butyrate when compared to the MUC group (p0.05). FOS supplementation reduced inflammatory infiltrate, partially preserved intestinal mucosa, reduced intestinal permeability, and increased levels of catalase. Pretreatment showed to be more efficient in the production of SCFA acetate and butyrate, indicating intestinal microbiota modulation time-dependent.