The role of NMDA glutamate receptors in lung injury caused by chronic long-term intermittent hypobaric hypoxia

• Published in: Brazilian journal of medical and biological research Vol. 56; no. 1; p. e12549
• Main Authors: Yaman, M O, Sönmez, O F, Ekiz-Yilmaz, T, Sönmez, D, Meydanlı, E E G, Guner, I, Sahin, G, Dariyerli, N, Yelmen, N
• Format: Journal Article
• Language: English
• Published: Brazil Associacao Brasileira de Divulgacao Cientifica (ABDC) 01.01.2023; Revista Brasileira de Pesquisas Medicas; Associação Brasileira de Divulgação Científica
• Subjects: Acute respiratory distress syndrome; Animals; Apnea; BIOLOGY; Blood levels; Bronchus; Caspase-9; Causes of; Complications and side effects; Development and progression; Dizocilpine; Dizocilpine Maleate - pharmacology; Fibrosis; Glutamate receptors; Glutamic Acid; Glutamic acid receptors (ionotropic); Glutathione peroxidase; Health aspects; Hypoxia; Hypoxia - complications; Inflammation; Interleukin-6 - metabolism; Lung Injury; Lungs; MEDICINE, RESEARCH & EXPERIMENTAL; Methyl aspartate; N-Methyl-D-aspartic acid receptors; N-Methylaspartate - pharmacology; Neurotransmitter receptors; Oxidants; Oxidants - pharmacology; Oxidative Stress; Rats; Receptors, Glutamate; Receptors, N-Methyl-D-Aspartate; Sleep disorders; Superoxide dismutase; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-TNF; Turkey; MK-801; NMDARs; Glutamate; Chronic long-term intermittent hypoxia; Lung injury
• ISSN: 0100-879X; 1414-431X; 1414-431X; 1678-4510
• DOI: 10.1590/1414-431X2023e12549

Chronic intermittent hypoxia (CIH), a component of sleep apnea-hypopnea syndrome, is suggested to cause damage to lung tissue, and the role of glutamate is not well studied. We used a chronic long-term intermittent hypobaric hypoxia (CLTIHH) model of rats to find out if such procedure causes lung injury and the potential effect of N-methyl-D-aspartate receptors (NMDARs) by using receptor antagonist MK-801 (dizocilpine). Thirty-two rats were placed into four groups; a control and three CLTIHH groups where rats were placed into a low-pressure chamber set to 430 mmHg for 5 h/day, 5 days/week, for 5 weeks. Only one group received MK-801 (0.3 mg/kg, ip) daily. We evaluated tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and nuclear factor (NF)-kB for the inflammatory process, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPX), total antioxidant status (TAS), and total oxidant status (TOS) for oxidative stress, and caspase-9 levels. Blood plasma, bronchoalveolar fluid (BALF), and lung tissue extracts were evaluated. Both oxidant and inflammatory parameters were significantly increased in all the mediums of the CLTIHH groups except the group that received MK-801. Significant evidence was collected on MK-801 alleviating the effect of CLTIHH. Histological evaluations revealed lung damage and fibrotic changes in the CLTIHH groups. It was first shown that the CLTIHH procedure caused chronic lung injury, and that inflammation and oxidant stress were influential in the formation of lung injury. Secondly, NMDAR antagonist MK-801 effectively inhibited the development of lung injury and fibrosis.