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Role of N-methyl-D-aspartate receptor in hyperoxia-induced lung injury

FeiGe Tang1, ShaoJie Yue, ZiQiang Luo

  • 1Department of Pediatrics, XinHua Hospital, Shanghai Second Medical University, Shanghai, China.

Pediatric Pulmonology
|September 16, 2005
PubMed

Insights

The NMDA receptor antagonist MK-801 protects neonatal rats from hyperoxia-induced lung injury by reducing inflammation and oxidative stress. Glutamate excitotoxicity plays a role in this lung injury.

Area of Science:

  • Pulmonary Medicine
  • Neuroscience
  • Toxicology

Background:

  • Glutamate (Glu) N-methyl-D-aspartate (NMDA) receptors are found in the lungs.
  • NMDA receptor antagonist MK-801 has shown potential in mitigating oxidant lung injury.
  • Hyperoxia-induced lung injury is a significant concern in neonatal care.

Purpose of the Study:

  • To investigate the role of Glu excitotoxicity in hyperoxia-induced lung injury.
  • To determine the pulmonary protective effects of the NMDA receptor antagonist MK-801 in neonatal rats.

Main Methods:

  • Neonatal rats were administered MK-801 or saline intraperitoneally daily.
  • Rats were exposed to hyperoxia (more than 95% oxygen in air) for 7 days.
  • Evaluated lung injury markers including wet-to-dry lung weight, BAL fluid analysis, myeloperoxidase activity, and pathological injury.

Main Results:

  • MK-801 treatment significantly reduced hyperoxia-associated increases in lung wet-to-dry weight, leukocyte and neutrophil counts, and protein and LDH levels in BAL fluid.
  • MK-801 administration attenuated total myeloperoxidase activity and improved lung pathology.
  • The treatment inhibited hyperoxia-induced increments in reactive oxygen species and NF-kappaB production.

Conclusions:

  • NMDA receptor antagonist MK-801 ameliorates hyperoxia-induced lung injury in neonatal rats.
  • The protective effects are associated with decreased reactive oxygen species and NF-kappaB.
  • Glutamate may play a critical role in hyperoxia-induced lung injury through NMDA receptor activation.

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