Search

Phosgene is a poorly water-soluble gas penetrating the lower respiratory tract which can induce acute lung injury characterized by a latent phase of fatal pulmonary edema. Pulmonary edema caused by phosgene is believed to be a consequence of oxidative stress and inflammatory responses. Ethyl pyruvate (EP) has been demonstrated to have anti-inflammatory and anti-oxidative properties in vivo and in vitro. The potential therapeutic role of EP in phosgene-induced pulmonary edema has not been addressed so far. In the present study, we aim to investigate the protective effects of EP on phosgene-induced pulmonary edema and the underlying mechanisms. Rats were administered with EP (40 mg kg(-1)) and RAW264.7 cells were also incubated with it (0, 2, 5 or 10 µm) immediately after phosgene (400 ppm, 1 min) or air exposure. Wet-to-dry lung weight ratio (W:D ratio), nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production, cyclooxygenase2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, and mitogen-activated protein kinases activities (MAPKs) were measured. Our results showed that EP treatment attenuated phosgene-induced pulmonary edema and decreased the level of NO and PGE(2) dose-dependently. Furthermore, EP significantly reduced COX-2 expression, iNOS expression and MAPK activation induced by phosgene. Moreover, specific inhibitors of MAPKs reduced COX-2 and iNOS expression induced by phosgene. These findings suggested that EP has a protective role against phosgene-induced pulmonary edema, which is mediated in part by inhibiting MAPK activation and subsequently down-regulating COX-2 and iNOS expression as well as decreasing the production of NO and PGE(2)., (Copyright © 2011 John Wiley & Sons, Ltd.)

Secreted phospholipase A(2) of group IIA (sPLA(2)-IIA) has been involved in a variety of inflammatory diseases, including acute lung injury. However, the specific role of sPLA(2)-IIA in phosgene-induced acute lung injury remains unidentified. The aim of the present study was to investigate the correlation between sPLA(2)-IIA activity and the severity of phosgene-induced acute lung injury. Adult male rats were randomly exposed to either normal room air (control group) or a concentration of 400 ppm phosgene (phosgene-exposed group) for there are 5 phosgene-exposed groups altogether. For the time points of 1, 3, 6, 12 and 24 h post-exposure, one phosgene-exposed group was sacrificed at each time point. The severity of acute lung injury was assessed by Pa(O2)/F(IO2) ratio, wet-to-dry lung-weight ratio, and bronchoalveolar lavage (BAL) fluid protein concentration. sPLA(2)-IIA activity in BAL fluid markedly increased between 1 h and 12 h after phosgene exposure, and reached its highest level at 6 h. Moreover, the trend of this elevation correlated well with the severity of lung injury. These results indicate that sPLA(2)-IIA probably participates in phosgene-induced acute lung injury.

Phosgene inhalation can induced pulmonary edema formation. The purpose of this study was to investigate cell of apoptosis in pulmonary edema mice induced by phosgene. Fifty-two BALB/c mice were random divided into a negative group and a positive group with 26 mice in each. Mice were exposed for 5 min to air and phosgene in the negative group and in the positive one, respectively. The dose of phosgene was 539 ppm. After 4 h of exposure, all mice were anesthetized. Lungs were analyzed for lung wet/dry weight ratio and pathological alternation. The method of isolation and culture of alveolar type II cells (ATII cells) was established to observe their apoptosis by electron microscope and flow cytometry. Apoptosis of lung cells was observed by DNA gel electrophoresis and TUNEL. The lung wet/dry weight ratio was significantly higher in the positive group (6.42 +/- 1.00) than in the negative group (4.25 +/- 0.47, p < 0.05). A large amount of fluid effusion was observed in the alveolus of mice induced by phosgene. Alveolar type II cells were identified by tannic acid staining and electron microscope. The apoptotic signs in alveolar type II cells, alveolar type I cells, eosinophils, macrophages, symphocytes, and ciliated cells were viewed under electron microscope in positive group. The ratio of apoptosis cells (40.26 +/- 7.74) in positive was higher than that (1.58 +/- 1.01, p < 0.001) in the negative group by flow cytometry. DNA ladder alternation was seen through DNA gel electrophoresis. Apoptosis of epithelia and vascular endothelia in lung were found by TUNEL. These results indicate that there is success in establishing a model of pulmonary edema and method of isolation and culture of AT II cells in BALB/c mice. Phosgene can induce apoptosis of cells in the lungs of BALB/c mice, and this indicates that pulmonary edema is related to apoptosis of lung cells in mice, induced by phosgene.

Secreted phospholipase A2 of group IIA (sPLA2-IIA) has been involved in a variety of inflammatory diseases, including acute lung injury. However, the specific role of sPLA2-IIA in phosgene-induced acute lung injury remains unidentified. The aim of the present study was to investigate the correlation between sPLA2-IIA activity and the severity of phosgene-induced acute lung injury. Adult male rats were randomly exposed to either normal room air (control group) or a concentration of 400 ppm phosgene (phosgene-exposed group) for there are 5 phosgene-exposed groups altogether. For the time points of 1, 3, 6, 12 and 24 h post-exposure, one phosgene-exposed group was sacrificed at each time point. The severity of acute lung injury was assessed by PaO2/FIO2 ratio, wet-to-dry lung-weight ratio, and bronchoalveolar lavage (BAL) fluid protein concentration. sPLA2-IIA activity in BAL fluid markedly increased between 1 h and 12 h after phosgene exposure, and reached its highest level at 6 h. Moreover, the trend of this elevation correlated well with the severity of lung injury. These results indicate that sPLA2-IIA probably participates in phosgene-induced acute lung injury. [ABSTRACT FROM AUTHOR]