PMID- 21818760
OWN - NLM
STAT- MEDLINE
DCOM- 20130507
LR  - 20131121
IS  - 1099-1263 (Electronic)
IS  - 0260-437X (Linking)
VI  - 33
IP  - 1
DP  - 2013 Jan
TI  - Ethyl pyruvate protects rats from phosgene-induced pulmonary edema by inhibiting 
      cyclooxygenase2 and inducible nitric oxide synthase expression.
PG  - 71-7
LID - 10.1002/jat.1713 [doi]
AB  - 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 microm) 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).
CI  - Copyright (c) 2011 John Wiley & Sons, Ltd.
FAU - Chen, Hong-li
AU  - Chen HL
AD  - Department of Toxicology, Fourth Military Medical University, Xi'an, 710032, 
      China.
FAU - Bai, Hua
AU  - Bai H
FAU - Xi, Miao-miao
AU  - Xi MM
FAU - Liu, Riu
AU  - Liu R
FAU - Qin, Xu-jun
AU  - Qin XJ
FAU - Liang, Xin
AU  - Liang X
FAU - Zhang, Wei
AU  - Zhang W
FAU - Zhang, Xiao-di
AU  - Zhang XD
FAU - Li, Wen-li
AU  - Li WL
FAU - Hai, Chun-xu
AU  - Hai CX
LA  - eng
PT  - Journal Article
DEP - 20110805
PL  - England
TA  - J Appl Toxicol
JT  - Journal of applied toxicology : JAT
JID - 8109495
RN  - 0 (Chemical Warfare Agents)
RN  - 0 (Protective Agents)
RN  - 0 (Pyruvates)
RN  - 03O98E01OB (ethyl pyruvate)
RN  - 117K140075 (Phosgene)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Bronchoalveolar Lavage Fluid/chemistry
MH  - Cell Line
MH  - Chemical Warfare Agents/toxicity
MH  - Cyclooxygenase 2/metabolism
MH  - Lung/*drug effects/pathology
MH  - Macrophages/drug effects/pathology
MH  - Male
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Nitric Oxide/analysis/metabolism
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Organ Size/drug effects
MH  - Phosgene/*toxicity
MH  - Protective Agents/*pharmacology
MH  - Pulmonary Edema/chemically induced/pathology/*prevention & control
MH  - Pyruvates/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2011/08/06 06:00
MHDA- 2013/05/08 06:00
CRDT- 2011/08/06 06:00
PHST- 2011/04/23 00:00 [received]
PHST- 2011/05/23 00:00 [revised]
PHST- 2011/05/23 00:00 [accepted]
PHST- 2011/08/06 06:00 [entrez]
PHST- 2011/08/06 06:00 [pubmed]
PHST- 2013/05/08 06:00 [medline]
AID - 10.1002/jat.1713 [doi]
PST - ppublish
SO  - J Appl Toxicol. 2013 Jan;33(1):71-7. doi: 10.1002/jat.1713. Epub 2011 Aug 5.