NMDA Receptor Antagonist Attenuates Bleomycin-Induced Acute Lung Injury

PLoS One. 2015 May 5;10(5):e0125873. doi: 10.1371/journal.pone.0125873. eCollection 2015.

Abstract

Background: Glutamate is a major neurotransmitter in the central nervous system (CNS). Large amount of glutamate can overstimulate N-methyl-D-aspartate receptor (NMDAR), causing neuronal injury and death. Recently, NMDAR has been reported to be found in the lungs. The aim of this study is to examine the effects of memantine, a NMDAR channel blocker, on bleomycin-induced lung injury mice.

Methods: C57BL/6 mice were intratracheally injected with bleomycin (BLM) to induce lung injury. Mice were randomized to receive saline, memantine (Me), BLM, BLM plus Me. Lungs and BALF were harvested on day 3 or 7 for further evaluation.

Results: BLM caused leukocyte infiltration, pulmonary edema and increase in cytokines, and imposed significant oxidative stress (MDA as a marker) in lungs. Memantine significantly mitigated the oxidative stress, lung inflammatory response and acute lung injury caused by BLM. Moreover, activation of NMDAR enhances CD11b expression on neutrophils.

Conclusions: Memantine mitigates oxidative stress, lung inflammatory response and acute lung injury in BLM challenged mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / chemically induced*
  • Acute Lung Injury / drug therapy
  • Acute Lung Injury / metabolism*
  • Acute Lung Injury / pathology
  • Amino Acids / metabolism
  • Animals
  • Antibiotics, Antineoplastic / adverse effects*
  • Bleomycin / adverse effects*
  • Bronchoalveolar Lavage Fluid
  • CD11b Antigen / metabolism
  • Capillary Permeability
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dopamine Agents / pharmacology
  • Female
  • Glutamic Acid / metabolism
  • Malondialdehyde / metabolism
  • Memantine / pharmacology
  • Mice
  • Neutrophil Infiltration
  • Neutrophils / metabolism
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*

Substances

  • Amino Acids
  • Antibiotics, Antineoplastic
  • CD11b Antigen
  • Cytokines
  • Dopamine Agents
  • Receptors, N-Methyl-D-Aspartate
  • Bleomycin
  • Glutamic Acid
  • Malondialdehyde
  • Memantine

Grants and funding

Funding from the National Natural Science Foundation of China (http://www.nsfc.gov.cn/) grant numbers 81270121, 30870916, 81100057; China Hnan Provincial Science & Technology Department, Provincial Natural Science Foundation of Hunan (http://www.hnst.gov.cn/zxgz/zkjj/) grant number 12JJ2049; the Education Department of Hunan Province, Innovation Fund for Institution of Higher Education of Hunan Province (http://gov.hnedu.cn/index.html) grant number 11K076; and Central South University, The Open-End Fund for the Valuable and Precision Instrument of Central South University (http://www.csu.edu.cn/) grant number 2012-02,2012-12. The funders had no role in design, data collection and analysis, decision to publish, or preparation of the manuscript.