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Soluble epoxide hydrolase is a therapeutic target for acute inflammation.


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.

SUBMITTER: Schmelzer KR 

PROVIDER: S-EPMC1168955 | biostudies-literature | 2005 Jul

REPOSITORIES: biostudies-literature

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Soluble epoxide hydrolase is a therapeutic target for acute inflammation.

Schmelzer Kara R KR   Kubala Lukas L   Newman John W JW   Kim In-Hae IH   Eiserich Jason P JP   Hammock Bruce D BD  

Proceedings of the National Academy of Sciences of the United States of America 20050630 28


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 m  ...[more]

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