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Matrix metalloproteinase inhibitor (ONO-4817) attenuates ischemia-reperfusion injury in rat lung

Takehiko Shimoyama, Noriyuki Tabuchi, Jihwa Chung, Takatoshi Koyama, Makoto Sunamori

Med Sci Monit 2006; 12(2): BR51-56

ID: 445227

Available online: 2006-02-01

Published: 2006-02-01

Background: Ischemia-reperfusion injury of the lungs seems to be initiatedby the activation of alveolar macrophages, and mediated by matrix metalloproteinases (MMP)s, althoughtheir roles have not been fully elucidated. Therefore, we used a novel MMP inhibitor (ONO-4817) withhigh affinities for MMP-2 and MMP-9 to investigate the roles of MMPs in reperfusion injury of the lungs.Material/Methods: After 18 h of cold ischemia, isolated rat lungs were ventilated and reperfused. Lungswithout ischemia served as controls. Lungs were reperfused with fresh blood with or without the MMP inhibitorfor 120 min at 37 degrees C. Results: The oxygenation capacity of lungs after ischemia deteriorated progressivelyduring 120 min of reperfusion, but was preserved by the MMP inhibitor (p

Keywords: Antigens, CD11c - metabolism, Animals, Antigens, CD31 - metabolism, Lung - physiopathology, Lung Injury, Macrophages, Alveolar - pathology, Matrix Metalloproteinase Inhibitors, Neutrophils - pathology, Phenyl Ethers - pharmacology, Protease Inhibitors - pharmacology, Rats, Rats, Sprague-Dawley, Reactive Oxygen Species - metabolism, Reperfusion Injury - prevention & control