L-Arginine Pretreatment Reduces Intestinal Mucositis as Induced by 5-FU in Mice

Abstract

Beneficial effects of L-arginine on immune responses and bowel function have been reported. Mucositis is a side effect of chemotherapy treatment that affects approximately 40% of patients. This complication is characterized by inflammation that affects the gastrointestinal tract, increasing permeability and causing abdominal pain, nausea, vomiting, and diarrhea, which worsen the patient's nutritional status and increases morbimortality. The aim of this study was to evaluate the effect of pretreating with 2% L-arginine supplementation in water on mucositis as induced by 5-fluorouracil (5-FU; a single dose of 200 mg/kg body weight) in Swiss male mice. The effect of L-arginine on weight, intestinal permeability, morphology, and the histopathological score of the small intestine (from 0 to 12), oxidative stress, myeloperoxidase (MPO), and N-acetylglucosaminidase (NAG) activities were evaluated. Intestinal length improvement was observed, in addition to the partial recovery of the mucosal architecture. L-arginine attenuated the histopathological score and MPO activity. There was also an improvement in intestinal permeability, despite weight loss after 5-FU administration. In conclusion, L-arginine can positively impact intestinal mucositis by promoting partial mucosal recovery, reducing inflammation and improving intestinal permeability.

Effects of commercially produced almond by-products on chemotherapy-induced mucositis in rats

“…This is presumably due to the increased cell-turnover rate which is a characteristic feature of the small intestine[ 3 ]. The main histological findings of villus shortening and crypt disruption caused by 5-FU administration were typical, and in concordance with other studies[ 27 - 29 ].…”

Alteration of Gut Microbiota and Inflammatory Cytokine/Chemokine Profiles in 5-Fluorouracil Induced Intestinal Mucositis

“…Inflammatory infiltration is a characteristic of mucositis, which is triggered by the increased adhesion molecules in intestinal endothelia that attract the circulating inflammatory cells including neutrophils, T lymphocyte cells, B lymphocyte cells to gather in the inflammatory sites (Erbeldinger et al, 2017 ; Kim et al, 2017 ). The inflammatory cells further accelerate the modification of tight junction, thereby increase intestinal permeability leading to the disruption of mucosal barrier (Leocádio et al, 2015 ). The elevated pro-inflammatory cytokines induced by 5-Fu have been shown to account for the loss of tight junction proteins of small intestine, such as occludin and claudin-1, and result in diarrhea (Patel et al, 2016 ).…”

“…Body weight, diarrhea and bloody stool of mice were recorded daily for the assessment of mucositis. Diarrhea grade was evaluated based on the consistency of stool, using the modified parameters as described previously (Leocádio et al, 2015 ): 0, normal; 1, slightly wet; 2, moderate wet; 3, loose; 4, watery stool. At the last day (day 7), the grade of blood stool was assessed by a commercial testing paper (BASO diagnostics Inc. China) with the following scores: 0, normal; 1, slight bleeding; 2, moderate bleeding; 3, severe bleeding; 4, visible bleeding.…”

Dietary supplementation with omega-3 fatty acid attenuates 5-fluorouracil induced mucositis in mice

“…The results changed according to the type or concentration of agent or substance used. Some studies showed that amino acids, such as arginine, glutamine and citrulline, can promote partial mucosal recovery after mucositis induction [ 43 – 45 ]. Probiotics and prebiotics have also been extensively studied in mucositis, but with controversial results [ 16 , 46 – 48 ].…”