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: Aline A da Cunha, Vânia Pauli, Vasyl C Saciura, Melissa G S Pires, Leandra C Constantino, Bruna de Souza, Fabricia Petronilho, Jarbas Rodrigues de Oliveira, Cristiane Ritter, Pedro R T Romão, Carina Rodrigues Boeck, Rafael Roesler, João Quevedo, Felipe Dal-Pizzol
• Journal: Chest (Chest) Vol. 137 Issue 2 Pg. 297-302 (Feb 2010) ISSN: 1931-3543 [Electronic] United States
• PMID: 19837828 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Excitatory Amino Acid Antagonists
• Receptors, N-Methyl-D-Aspartate
• Dizocilpine Maleate

Topics

• Animals
• Disease Models, Animal
• Dizocilpine Maleate (administration & dosage, therapeutic use)
• Dose-Response Relationship, Drug
• Excitatory Amino Acid Antagonists (administration & dosage, therapeutic use)
• Lung Injury (drug therapy, etiology, metabolism)
• Male
• Oxidative Stress (drug effects)
• Rats
• Rats, Wistar
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)
• Sepsis (complications)
• Treatment Outcome