Efeitos do uso vitamina c isolada e associada à arginina em modelo experimental de mucosite induzida por 5-fluorouracil.

Abstract

Intestinal mucositis is collateral damage caused by the chemotherapy or radiotherapy treatments that cancer patients are undergoing. Until now there are no efficient alternatives to minimize or prevent the damage caused by mucositis. Thus, the use of immunomodulators has been the target of studies to evaluate its role in this problem. The aim of this study was to evaluate the effects of vitamin C supplementation alone and associated with L-arginine on experimental intestinal mucositis induced by 5-FU. Male Balb/c mice 6 to 7 weeks old, receiving standard diet and water were divided into 4 groups: Control (CTL), Mucositis (MUC), Mucositis + Vitamin C (MUC+VIT), Mucositis + association of arginine and vitamin C (MUC+ARG+VIT). Mice in the CTL and MUC groups received 0.2 mL of saline (NaCl 99%) by gavage throughout the experimental period. The animals in the MUC+VIT and MUC+ARG+VIT groups received by gavage 0.2 mL of a solution of 60 mg of vitamin C and 60 mg of vitamin C associated of 60 mg of arginine, respectively. On the 7th day the animals in the MUC, MUC+VIT and MUC+ARG+VIT groups received i.p. injection of 300mg/kg of 5-Fu in a single dose. After 72 hours the animals were anesthetized and euthanized by cervical dislocation and samples of tissues and blood were collected for analysis. The mice with mucositis showed a significant reduction in weight and consumption when compared to the animals CTL. The MUC group showed higher intestinal permeability (IP) when compared to CTL, and the groups with both treatments were able to preserve the PI at physiological levels. The administration of chemotherapy did not affect the expression of the ZO-1 junction in none of the groups, while the expression of occludin decreased in all groups with mucositis when compared to the CTL group. Vitamin C supplementation alone showed better results in histological analysis, with maintenance of intestinal architecture and villi and crypts. Eosinophilic peroxidase (EPO) and myeloperoxidase (MPO) increased activities were observed in the animals of the MUC group. However, only vitamin C treatment prevented the inflammatory infiltrate. The concentration of sIgA decreased in the groups with mucositis, and a partial increase was observed in both treatments. Gene expression of NFkB, TNFα and COX2 was significantly higher in the MUC group compared to CTL. The MUC+VIT group showed similar gene expression to CTL. However, there was no statistically significant difference between the MUC and MUC+ARG+VIT groups for the expression of TNFα and COX2. Additionally, the expression of the cytokines IL1β, IL10 and IL6 did not show any statistical difference among the groups. Oxidative stress analysis showed increased activity of the enzymes SOD, TBARS, and hydroperoxides in the MUC group. However, supplementation with both treatments maintained only TBARS activity at basal levels. The use of the association between vitamin C and L-arginine did not present additional benefits to affirm that the use of the association would be better than the monotherapies, since the use of vitamin C alone presented more benefits than the association of this immunomodulators.