TY - JOUR
T1 - Participation of the anti-inflammatory and antioxidative activity of docosahexaenoic acid on indomethacin-induced gastric injury model
AU - Pineda-Peña, Elizabeth Arlen
AU - Martínez-Pérez, Yoalli
AU - Galicia-Moreno, Marina
AU - Navarrete, Araceli
AU - Segovia, José
AU - Muriel, Pablo
AU - Favari, Liliana
AU - Castañeda-Hernández, Gilberto
AU - Chávez-Piña, Aracely Evangelina
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2018/1/5
Y1 - 2018/1/5
N2 - 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 100 mg/kg) caused a reduction in indomethacin-induced gastric hemorrhagic lesions. We found that the gastroprotective effects of DHA treatment (100 mg/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.
AB - 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 100 mg/kg) caused a reduction in indomethacin-induced gastric hemorrhagic lesions. We found that the gastroprotective effects of DHA treatment (100 mg/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.
KW - Anti-inflammatory
KW - DHA
KW - Docosahexaenoic acid
KW - Gastric injury
KW - Indomethacin
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=85034834330&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2017.11.015
DO - 10.1016/j.ejphar.2017.11.015
M3 - Artículo
C2 - 29154839
AN - SCOPUS:85034834330
SN - 0014-2999
VL - 818
SP - 585
EP - 592
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -