title: Pretreatment With L-Citrulline Positively Affects the Mucosal Architecture and Permeability of the Small Intestine in a Murine Mucositis Model.
abstract: BACKGROUND
  Mucositis is a common complication in patients undergoing radiotherapy and chemotherapy. It is associated with pain, poor quality of life, and malnutrition, leading to an increased number of hospital admissions and prolonged hospitalization. The use of immunonutrients may be an alternative treatment option, which may help to improve patient outcome.
  
  
  OBJECTIVE
  Here we assessed the impact of L-citrulline (CIT) on a murine model of 5-fluorouracil (5FU)-induced mucositis.
  
  
  METHODS
  Swiss male mice were randomized into 4 groups: control, CIT, 5FU, and 5FU+CIT. Mice were fed with commercial chow and supplemented with an oral solution of alanine (control and 5FU groups) or CIT (CIT and 5FU+CIT groups). On the seventh day, mice received intraperitoneal phosphate-buffered saline or 5FU (200 mg/kg, single dose) to induce mucositis. On the 10th day, mice were euthanized, and the blood and small intestines were harvested. Body weight, morphology, histopathology score (hematoxylin and eosin) of the small intestine (from 0-12), myeloperoxidase activity, oxidative stress level, and intestinal permeability were assessed.
  
  
  RESULTS
  We observed significant weight loss after the administration of 5FU in both treated and control animals. CIT administration contributed to a partial recovery of the mucosal architecture as well as an intermediate reduction of the histopathologic score, and functional intestinal permeability was partially rescued.
  
  
  CONCLUSIONS
  CIT administration attenuated 5FU-mediated damage to the mucosal architecture of the small intestine, decreasing the size of the injured areas and promoting decreased intestinal permeability.
authors.affiliation: Departamento de Ciência de Alimentos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte-MG, Brazil maisaantunes@gmail.com.
authors.forename: Maísa Mota
authors.initials: MM
authors.lastname: Antunes
authors.affiliation: Departamento de Ciência de Alimentos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte-MG, Brazil.
authors.forename: Paola Caroline Lacerda
authors.initials: PC
authors.lastname: Leocádio
authors.affiliation: Departamento de Ciência dos Alimentos, Setor de Nutrição, Universidade Federal de Lavras, Lavras-MG, Brazil.
authors.forename: Lílian Gonçalves
authors.initials: LG
authors.lastname: Teixeira
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte-MG, Brazil.
authors.forename: Alda Jusceline
authors.initials: AJ
authors.lastname: Leonel
authors.affiliation: Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte-MG, Brazil.
authors.forename: Denise Carmona
authors.initials: DC
authors.lastname: Cara
authors.affiliation: Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte-MG, Brazil.
authors.forename: Gustavo Batista
authors.initials: GB
authors.lastname: Menezes
authors.affiliation: Departamento de Nutrição, Escola de Enfermagem, Universidade Federal de Minas Gerais, Belo Horizonte-MG, Brazil.
authors.forename: Simone de Vasconcelos
authors.initials: Sde V
authors.lastname: Generoso
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte-MG, Brazil.
authors.forename: Valbert Nascimento
authors.initials: VN
authors.lastname: Cardoso
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte-MG, Brazil.
authors.forename: Jacqueline Isaura
authors.initials: JI
authors.lastname: Alvarez-Leite
authors.affiliation: Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte-MG, Brazil.
authors.forename: Maria Isabel Toulson Davisson
authors.initials: MI
authors.lastname: Correia
mesh_terms: D000818:Animals; D002956:Citrulline / Q000494:pharmacology*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005472:Fluorouracil / Q000009:adverse effects; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D052016:Mucositis / Q000139:chemically induced / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects; D010539:Permeability
chemical_list: D002956:Citrulline; D005472:Fluorouracil
keywords: 5FU; L-citrulline; intestinal permeability; mucositis