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Proc Natl Acad Sci U S A. 2005 Jul 12;102(28):9772-7. Epub 2005 Jun 30.

Soluble epoxide hydrolase is a therapeutic target for acute inflammation.

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1
Department of Entomology, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA.

Abstract

As of 2004, >73 million people were prescribed antiinflammatory medication. Despite the extensive number of current products, many people still suffer from their diseases or the pharmacological properties (side effects) of the medications. Therefore, developing therapeutic strategies to treat inflammation remains an important endeavor. Here, we demonstrate that the soluble epoxide hydrolase (sEH) is a key pharmacologic target for treating acute systemic inflammation. Lipopolysaccharide-induced mortality, systemic hypotension, and histologically evaluated tissue injury were substantially diminished by administration of urea-based, small-molecule inhibitors of sEH to C57BL/6 mice. Moreover, sEH inhibitors decreased plasma levels of proinflammatory cytokines and nitric oxide metabolites while promoting the formation of lipoxins, thus supporting inflammatory resolution. These data suggest that sEH inhibitors have therapeutic efficacy in the treatment and management of acute inflammatory diseases.

PMID:
15994227
PMCID:
PMC1168955
DOI:
10.1073/pnas.0503279102
[Indexed for MEDLINE]
Free PMC Article
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