Dose dependent decrease in LTB4 formation of rat leukocytes by the administration of EPA ethyl ester.
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概要
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To clarify the anti-inflammatory effect of eicosa-pentaenoic acid (EPA), we investigated the effect of EPA administration on A23187-stimulated LTB<SUB>4</SUB> formation by rat leukocytes. LTB<SUB>4</SUB> is known to be an important mediator of inflammation and the decreased formation of LTB<SUB>4</SUB> is thought to be one of the important mechanism of anti-inflammatory effect of EPA. EPA ethyl ester (EPA-E) administration (100 mg, 300 mg and 1, 000 mg/kg/day) for 4 weeks dose dependently suppressed the formation of LTB<SUB>4</SUB> and increase in the formation of LTB<SUB>5</SUB> with the increase in EPA content in rat leukocytes. The content of docosapentaenoic acid (DPA) also dose-dependently increased and the content of arachidonic acid (AA) and docosahexaenoic acid (DHA) were decreased by the administration of 300 mg and 1000 mg of EPA-E daily. The formation of LTB<SUB>4</SUB> in stimulated leukocytes and the content of AA are positively correlated.<BR>FMLP-induced chemotactic activity of leukocytes were suppressed with the EPA-E treatment but FMLP stimulated β-glucuronidase release was not affected by EPA administration.<BR>In conclusion, highly purified EPA-E administration reduced the formation of proinflammatory LTB<SUB>4</SUB>, increased the LTB<SUB>5</SUB>, which would competitively inhibit the action of LTB<SUB>4</SUB> and suppressed the chemotactic activity of leukocytes, these might result in the suppression of inflammatory response.
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