Epoxyeicosatrienoic acids and soluble epoxide hydrolase: potential therapeutic targets for inflammation and its

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Enzymatic Synthesis of Epoxidized Metabolites of Docosahexaenoic, Eicosapentaenoic, and Arachidonic Acids
13:05

Enzymatic Synthesis of Epoxidized Metabolites of Docosahexaenoic, Eicosapentaenoic, and Arachidonic Acids

Published on: June 28, 2019

Stephanie Norwood, Jie Liao, Bruce D Hammock

    American Journal of Translational Research
    |August 25, 2010
    PubMed

    Insights

    Soluble epoxide hydrolase (sEH) inhibition reduces inflammation and ulceration in colitis models. Increased sEH expression in human ulcerative colitis suggests it is a potential therapeutic target for inflammation-induced carcinoma.

    Area of Science:

    • Biochemistry and Molecular Biology
    • Inflammation and Immunology
    • Gastroenterology and Oncology

    Background:

    • Chronic inflammation is a key driver in human carcinoma development.
    • Non-steroidal anti-inflammatory drugs (NSAIDs) show chemopreventive effects but carry cardiovascular risks.
    • Soluble epoxide hydrolase (sEH) metabolizes anti-inflammatory epoxyeicosatrienoic acids (EETs) into less active forms.

    Purpose of the Study:

    • To investigate the role of sEH in inflammation and inflammation-induced carcinoma.
    • To evaluate the therapeutic potential of sEH inhibition for ulcerative colitis and associated dysplasia/carcinoma.

    Main Methods:

    • Administration of a selective sEH inhibitor (sEHI) in mouse colitis models.
    • Assessment of ulcer incidence and number in treated versus control mice.
    • Immunohistochemical analysis of sEH expression in human ulcerative colitis (UC), UC-induced dysplasia, and UC-induced carcinoma tissues.

    Main Results:

    • sEH inhibition significantly decreased ulcer incidence and the number of ulcers in mouse colitis models.
    • No adverse side effects were observed with sEHI administration in the mouse models.
    • sEH expression was notably increased in human UC, UC-induced dysplasia, and UC-induced carcinoma tissues.

    Conclusions:

    • Inhibition of sEH effectively reduces inflammation and associated tissue damage in preclinical models.
    • Elevated sEH expression in human UC and related cancers indicates its potential as a therapeutic target.
    • sEH inhibition represents a promising novel strategy for managing inflammation and preventing inflammation-induced carcinoma.
    Keywords:
    Epoxyeicosatrienoic acids (EETs)cancercarcinogenesisdihydroxyeicosatrienoic acids (DHETs)inflammationnon-steroidal anti-inflammatory drugs (NSAIDs)soluble epoxide hydrolase (sEH)therapy

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