Tuberc Respir Dis.  2000 Feb;48(2):246-259. 10.4046/trd.2000.48.2.246.

Effect of the inhibition of PLA2 on the oxidative stress in the lungs of glutathione depleted rats given endotoxin intratracheally

• Cho HG
• Moon HJ
• Park WH
• Kim TO
• Lee YM

• KMID: 1877193
• DOI: http://doi.org/10.4046/trd.2000.48.2.246

Abstract

BACKGROUND: As one of the etiologies of acute respiratory distress syndrome (ARDS), sepsis is one of the morbid causes of this cryptogenic malady. Even though many documents on the role of endotoxin (ETX) in the pathogenesis of ARDS have been issued, still the underlying mechanism associated with oxidative stress and activation of PLA2 has been a controversy controversial . In the present study, the role of phospholipase A2 (PLA2) in the neutrophilic respiratory burst(,) which is presumed to cause acute lung injury during sepsis(,) was probed. METHOD: In glutathione (-)depleted Sprague-Dawley rats, lung leak, infiltration of neutrophils, PLA2 activity and lipid peroxidation in the lung were measured after intratracheal instillation of endotoxin intratracheally (delete). In addition, gamma glutamyl transferase (GGT) activity and the amount of pulmonary surfactant were measured. Morphologically, changes of the changes in ultrastructure and cytochemical demonstration of oxidants were presented to confirm the neutrophilic oxidative stress and to elucidate the effects of the activation of PLA2 activation on the (delete) oxidative stress. RESULTS: Instillation of ETX to glutathione (-) depleted rats intensified lung leak and lipid peroxidation when compared with non-glutathione depleted rats treated with the endotoxin. Moreover, oxidative stress was confirmed by the assay of GGT and malondialdehyde. Functionally, the depletion of glutathione altered the secretion of pulmonary surfactant from alveolar type II cells. Ultrastructurally and cytochemically, oxidative stress was also confirmed after treatment of with ETX and diethylmaleate (DEM). CONCLUSION: The endotoxin-induced acute lung injury was mediated by oxidative stress(,) which in turn was provoked by the neutrophilic respiratory burst. The activation of PLA2 in the lung seems to play the a pivotal role in the oxidative stress of the lung.

Keyword

ARDS; neutrophil; oxidative stress; PLA2

MeSH Terms

Acute Lung Injury
Animals
Glutathione*
Lipid Peroxidation
Lung*
Malondialdehyde
Neutrophils
Oxidants
Oxidative Stress*
Phospholipases A2
Pulmonary Surfactants
Rats*
Rats, Sprague-Dawley
Respiratory Burst
Respiratory Distress Syndrome, Adult
Sepsis
Transferases
Glutathione
Malondialdehyde
Oxidants
Phospholipases A2
Pulmonary Surfactants
Transferases