Document Detail

The spin trap 5,5-dimethyl-1-pyrroline N-oxide inhibits lipopolysaccharide-induced inflammatory response in RAW 264.7 cells.
MedLine Citation:
PMID:  22285597     Owner:  NLM     Status:  MEDLINE    
AIM: Exposure of macrophages to lipopolysaccharide (LPS) induces oxidative and inflammatory stresses, which cause cell damage. Antioxidant and anti-inflammatory properties have been attributed to the nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), commonly used in free radical analysis, but these aspects of DMPO have been little explored. In this study, we sought to establish the anti-inflammatory activity of DMPO, presumably by removing free radicals which otherwise help activate inflammatory response and damage cells.
MAIN METHODS: RAW 264.7 macrophages were treated with LPS and/or DMPO for different time points, cell damage, production of inflammatory mediators, inducible nitric oxide synthase (iNOS) expression, NF-κB p65 activation, phosphorylation of MAPKs and Akt, and intracellular reactive oxygen species (ROS) were determined.
KEY FINDINGS: After cells were treated with LPS and/or DMPO for 24 h, DMPO reduced the LPS-induced inflammatory response as indicated by downregulated iNOS expression and production of inflammatory mediators. Accordingly, DMPO protected cells from LPS-induced cytotoxicity. In order to understand the mechanistic basis of these DMPO effects, the NF-κB p65 activation and the phosphorylation of MAPKs and Akt were examined. We found, by assaying cells treated with LPS and/or DMPO for 15-60 min, that DMPO inhibited the phosphorylation of MAPKs, Akt, and IκBα, and reduced the NF-κB p65 translocation. Furthermore, we demonstrated that DMPO inhibited LPS-induced ROS production.
SIGNIFICANCE: DMPO showed the anti-inflammatory activity and attenuated LPS-induced cell damage, most likely by reducing ROS production and thus preventing the subsequent inflammatory activation and damage.
Zili Zhai; Sandra E Gomez-Mejiba; Hua Zhu; Florea Lupu; Dario C Ramirez
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-01-17
Journal Detail:
Title:  Life sciences     Volume:  90     ISSN:  1879-0631     ISO Abbreviation:  Life Sci.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-06     Completed Date:  2012-04-23     Revised Date:  2014-09-09    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  432-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Anti-Inflammatory Agents / pharmacology*
Blotting, Western
Cell Line, Tumor
Cyclic N-Oxides / pharmacology*
Inflammation / chemically induced,  prevention & control*
Lipopolysaccharides / toxicity
Macrophages / drug effects
Nitric Oxide Synthase Type II / metabolism
Nitrites / metabolism
Reactive Oxygen Species / metabolism
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Spin Labels*
Grant Support
5R00ES015415-04/ES/NIEHS NIH HHS; R00 ES015415/ES/NIEHS NIH HHS; R00 ES015415-04/ES/NIEHS NIH HHS
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Cyclic N-Oxides; 0/Lipopolysaccharides; 0/Nitrites; 0/Reactive Oxygen Species; 0/Spin Labels; 7170JZ1QF3/5,5-dimethyl-1-pyrroline-1-oxide; EC Oxide Synthase Type II; EC protein, mouse

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