title: N-methyl-D-aspartate glutamate receptor blockade attenuates lung injury associated with experimental sepsis.
abstract: BACKGROUND
  The aim of this study was to examine the effects of the N-methyl-D-aspartate receptor (NMDAR) channel blocker dizocilpine (MK-801) on lung injury in rats submitted to experimental sepsis induced by cecal ligation and perforation (CLP).
  
  
  METHODS
  Adult male Wistar rats submitted to CLP were given a single systemic injection of MK-801 (subcutaneously at 0.3 mg/kg) administered 4 or 7 h after CLP induction. Twelve hours after CLP BAL was performed to determine total cell count, protein content, and inflammatory parameters. In addition, lung was excised for histopathologic analyses and determination of NMDAR subunits content. In a separate cohort of animals mortality was recorded for 5 days.
  
  
  RESULTS
  Animals submitted to sepsis induced by CLP showed an increase in the content of NMDAR subunits NR1 and NR2A in the lung. Administration of MK-801 4 h after CLP induction resulted in a decrease in BAL fluid cellular content and decreased levels of proinflammatory cytokines. In addition, MK-801 decreased lung oxidative stress markers and histopathologic alterations and improved survival.
  
  
  CONCLUSIONS
  These findings indicate that NMDAR blockade might represent a promising novel therapeutic strategy for the treatment of sepsis and inflammatory disorders.
authors.affiliation: Laboratório de Pesquisa em Biofísica Celular e Inflamação, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Aline A
authors.initials: AA
authors.lastname: da Cunha
authors.forename: Vânia
authors.initials: V
authors.lastname: Pauli
authors.forename: Vasyl C
authors.initials: VC
authors.lastname: Saciura
authors.forename: Melissa G S
authors.initials: MG
authors.lastname: Pires
authors.forename: Leandra C
authors.initials: LC
authors.lastname: Constantino
authors.forename: Bruna
authors.initials: B
authors.lastname: de Souza
authors.forename: Fabricia
authors.initials: F
authors.lastname: Petronilho
authors.forename: Jarbas
authors.initials: J
authors.lastname: Rodrigues de Oliveira
authors.forename: Cristiane
authors.initials: C
authors.lastname: Ritter
authors.forename: Pedro R T
authors.initials: PR
authors.lastname: Romão
authors.forename: Carina Rodrigues
authors.initials: CR
authors.lastname: Boeck
authors.forename: Rafael
authors.initials: R
authors.lastname: Roesler
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D055370:Lung Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D018805:Sepsis / Q000150:complications*; D016896:Treatment Outcome
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate