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).