Effects of high dose of dexamethasone on PLA2, GGT activityand lung morphology in NNNMU-induced ARDS rats

Man Lee, Young; Park, Yoon Yub; Koh, Younsuck

Abstract

Background
In order to elucidate one of the pathogenic mechanisms of ARDS associated with pulmonary surfactant and oxidant injury, acute lung injury was induced by N-nitroso- N-methylurethane (NNNMU). In this model, the role of phospholipase A2 (PLA2), surfactant, gamma glutamyl transferase (GGT) and morphology were investigated to delineate one of the pathogenic mechanisms of ARDS by inhibition of PLA2 with high dose of dexamethasone. Method: Acute lung injury was induced in Sprague-Dawley rats by NNNMU which is known to induce acute lung injury in experimental animals. To know the function of the alveolar type II cells, GGT activity in the lung and bronchoalveolar lavage was measured. Surfactant phospholipid was measured also. PLA2 activity was measured to know the role of PLA2 in ARDS. Morphological study was performed to know the effect of PLA2 inhibition on the ultrastructure of the lung by high dose of dexamethasone.
Results
Six days after NNNMU treatment (4 mg/kg), conspicuous pulmonary edema was induced and the secretion of pulmonary surfactant was decreased significantly. In the acutely injured rats' lung massive infiltration of leukocytes was observed. At the same time rats given NNNMU had increased PLA2 and GGT activity tremendously. Morphological study revealed bizarre shaped alveolar type II cells and hypertrophied lamellar bodies in the cytoplasm of the alveolar type II cells. But after dexamethasone treatment (20 mg/kg, for six days) in NNNMU-treated rats, these changes were diminished i.e. there were decrease of pulmonary edema and increase of surfactant secretion from alveolar type II cells. Rats given dexamethasone and NNNMU had decreased PLA2 and GGT activity in comparison to NNNMU induced ARDS rats.
Conclusion
Inhibition of PLA2 by high dose of dexamethasone decreased pathological findings caused by infiltration of leukocytes and respiratory burst. Based on these experimental results, it is suggested that an activation of PLA2 is the one of the major factors to evoke the acute lung injury in NNNMU-induced ARDS rats.