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Participation of the anti-inflammatory and antioxidative activity of docosahexaenoic acid on indomethacin-induced gastric injury model
Adverse gastrointestinal (GI) effects caused by nonsteroidal anti-inflammatory drugs (NSAIDs), including indomethacin, are recognized as the major limitation to their clinical use. NSAID-induced gastric damage is generated by cyclooxygenase inhibition, activation of inflammatory processes, and oxida...
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Published in: | European journal of pharmacology 2018-01, Vol.818, p.585-592 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Adverse gastrointestinal (GI) effects caused by nonsteroidal anti-inflammatory drugs (NSAIDs), including indomethacin, are recognized as the major limitation to their clinical use. NSAID-induced gastric damage is generated by cyclooxygenase inhibition, activation of inflammatory processes, and oxidative stress. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, has shown gastroprotective effects; however, the molecular mechanisms underlying these effects have not been fully explained. As a result, the aim of this study was to examine DHA's anti-inflammatory and antioxidative actions in a mouse model of indomethacin-induced gastric injury. Oral administration of DHA (3, 10, 30, and 100mg/kg) caused a reduction in indomethacin-induced gastric hemorrhagic lesions. We found that the gastroprotective effects of DHA treatment (100mg/kg) were accompanied by decreases in several parameters: in leukocyte recruitment; gastric levels of myeloperoxidase; leukotriene B4; intercellular adhesion molecule-1; tumor necrosis factor alpha; and nuclear translocation of nuclear factor-кB. Concurrently, we observed an improvement in antioxidant defenses produced by the increase in superoxide dismutase and glutathione activities but not catalase; in addition, a decrease in some oxidative damage markers such as malondialdehyde and carbonyl proteins in lipids and proteins was observed. Furthermore, resolvin D1 production and expression of free fatty acid receptor 4 were stimulated by DHA. Therefore, this study identified the antioxidant and anti-inflammatory actions of DHA as the main mechanisms involved in DHA's gastroprotective effects against indomethacin-induced gastric damage. |
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ISSN: | 0014-2999 1879-0712 |
DOI: | 10.1016/j.ejphar.2017.11.015 |