Hydrogen Peroxide Modulates Phospholipase A2 Aactivity and Endogenous Oxidative Stress in the Free Radical Induced Acute Lung Injury / 대한흉부외과학회지

ABSTRACT

BACKGROUND: In an attempt to investigate the role of oxidants in the activation of phospholipase A2(PLA2) and endogenous oxidative stress in the lung, acute inflammatory lung injury was induced by the instillation of hydrogen peroxide into the trachea of Sprague-Dawley rats. MATERIAL AND METHOD: To prove the hypothesis that released oxidants from neutrophils activate the PLA2 retrogradely, activities of PLA2 and lysoplatelet activating factor acetyltransferase(lysoPAF AT) were assayed 5 hours after instillation of hydrogen peroxide. In addition, to confirm the impairing effects of the activation of PLA2 associated with endogenous oxidative stress, lung weight/body weight ratio(Lx10(-3)/B), protein contents(mg/two lungs) in bronchoalveolar lavage(BAL) were measured. As neutrophilic respiratory burst has been known to play a pivotal role in the genesis of endogenous oxidative stress associated with acute inflammatory lung injury, BAL neutrophils counts and level of lung myelperoxidase(MPO) were measured after hydrogen peroxide insult. Morphological and histochemical studies were also performed to identify the effect of the endogenous oxidative stress. RESULT: Five hours after hydrogen peroxide instillation, lungs showed marked infiltration of neutrophils and increased weight. Protein contents in BAL increased significantly compared to those of normal rats. PLA2 activity was enhanced in the hydrogen peroxide instilled group. Interestingly, the accelerated production of platelet activating factor(PAF) was confirmed by the increased activity of lysoPAF AT in the H2O2 employed lung. Morphologically, light microscopic findings of lungs after instillation of hydrogen peroxide showed atelectasis and infiltration of inflammatory cells, which was thought to be caused by lipid mediators produced by PLA2 activation. In cerium chloride cytochemical electron microscopy, dense deposits of cerrous perhydroxide were identified. In contrast, no deposit of cerrous perhydroxide was found in the normal lung. CONCLUSION: As all these findings were consistent with the lung injury caused by neutrophilic oxidative stress, it is suggested that the activation of PLA2 by oxidants might participate in the genesis of endogenous oxidative stress. Collectively, the positive feedback loop between oxidative stress and PLA2 activation may participate in the pathogenesis of Adult Respiratory Distress Syndrome(ARDS).