Background
Ethyl pyruvate (EP) has been shown to attenuate lipopolysaccharide (LPS)-induced acute
lung injury (ALI). Induction of heme oxygenase-1 (HO-1) and suppression of inducible
nitric oxide synthase (iNOS) expression provide cytoprotection in lung and vascular
injury. The aim of this study is to evaluate whether the beneficial effect of EP on
lung inflammation is related to HO-1 induction in a rat model of LPS-induced ALI.
Materials and Methods
Rats were administered LPS (30 mg/kg) by intravenous infusion for 4 h to induce ALI.
EP (20, 40, and 60 mg/kg/4 h i.v. infusion) or vehicle was given 1 h after LPS initiation.
Results
EP 40 and 60 mg/kg attenuated plasma levels of TNF-α and IL-6 caused by LPS, and further
increased IL-10 levels compared with the LPS group. At 6 h after LPS initiation, iNOS
protein expression in lungs and plasma NO metabolite levels were markedly increased,
which were reduced by EP 60 mg/kg. LPS caused a significant HO-1 induction, whereas
administration of EP 60 mg/kg significantly induced higher HO-1 expression compared
with the LPS group. The beneficial effects of EP on cytokines and iNOS expression
were reversed by HO-1 inhibitor SnPP. EP significantly suppressed phosphorylated p38
MAPK and increased phosphorylated ERK1/2 protein levels in the lung tissue. The edema
and infiltration of neutrophils into lungs was reduced by EP.
Conclusion
EP reduced LPS-induced ALI, which may be mediated by induction of HO-1. The underlying
mechanisms are associated with suppression of p38 MAPK and increase of ERK1/2 signaling
pathway activation.
Key Words
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Article info
Publication history
Published online: February 03, 2011
Received:
October 14,
2010
Identification
Copyright
© 2011 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
