| The spin trap 5,5-dimethyl-1-pyrroline N-oxide inhibits lipopolysaccharide-induced inflammatory response in RAW 264.7 cells. | |
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MedLine Citation:
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PMID: 22285597 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Zili Zhai; Sandra E Gomez-Mejiba; Hua Zhu; Florea Lupu; Dario C Ramirez |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-01-17 |
Journal Detail:
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Title: Life sciences Volume: 90 ISSN: 1879-0631 ISO Abbreviation: Life Sci. Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-03-06 Completed Date: 2012-04-23 Revised Date: 2012-10-09 |
Medline Journal Info:
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Nlm Unique ID: 0375521 Medline TA: Life Sci Country: Netherlands |
Other Details:
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Languages: eng Pagination: 432-9 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Experimental Therapeutics Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. zlzhai@yahoo.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Inflammatory Agents / pharmacology* Blotting, Western Cell Line, Tumor Cyclic N-Oxides / pharmacology* Inflammation / chemically induced, prevention & control* Lipopolysaccharides / toxicity Macrophages / drug effects Mice 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 | |
ID/Acronym/Agency:
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5R00ES015415-04/ES/NIEHS NIH HHS; R00 ES015415/ES/NIEHS NIH HHS; R00 ES015415-04/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents; 0/Cyclic N-Oxides; 0/Lipopolysaccharides; 0/Nitrites; 0/Reactive Oxygen Species; 0/Spin Labels; 3317-61-1/5,5-dimethyl-1-pyrroline-1-oxide; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos2 protein, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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