Ethyl pyruvate protects rats from phosgene-induced pulmonary edema by inhibiting cyclooxygenase2 and inducible nitric oxide synthase expression.

Abstract

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).

• Authors: Hong-li Chen, Hua Bai, Miao-miao Xi, Riu Liu, Xu-jun Qin, Xin Liang, Wei Zhang, Xiao-di Zhang, Wen-li Li, Chun-xu Hai
• Journal: Journal of applied toxicology : JAT (J Appl Toxicol) Vol. 33 Issue 1 Pg. 71-7 (Jan 2013) ISSN: 1099-1263 [Electronic] England
• PMID: 21818760 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 John Wiley & Sons, Ltd.

Chemical References

• Chemical Warfare Agents
• Protective Agents
• Pyruvates
• ethyl pyruvate
• Phosgene
• Nitric Oxide
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Bronchoalveolar Lavage Fluid (chemistry)
• Cell Line
• Chemical Warfare Agents (toxicity)
• Cyclooxygenase 2 (metabolism)
• Lung (drug effects, pathology)
• Macrophages (drug effects, pathology)
• Male
• Mitogen-Activated Protein Kinases (metabolism)
• Nitric Oxide (analysis, metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Organ Size (drug effects)
• Phosgene (toxicity)
• Protective Agents (pharmacology)
• Pulmonary Edema (chemically induced, pathology, prevention & control)
• Pyruvates (pharmacology)
• Rats
• Rats, Sprague-Dawley