Antioxidative and anti-inflammatory actions of docosahexaenoic acid and eicosapentaenoic acid in renal epithelial cells and macrophages.
Oxidative stress due to excessive reactive species (RS) and weakened antioxidant defenses is causally associated with inflammation and inflammatory mediators. To investigate the effects of the major fish oil ingredients, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on oxidative stress-related inflammatory status, we conducted in vitro experiments utilizing rat renal epithelial cells (NRK-52E) and murine macrophages (RAW 264.7) by assessing their effects on the generation of cyclooxygenase (COX)-2-derived and xanthine oxidase (XOD)-derived RS, reduced glutathione (GSH) levels, and antioxidative enzyme activities. Additionally, 6-keto-prostaglandin (PG) F1alpha, PGE2, and nitrite levels were measured in lipopolysaccharide-stimulated RAW 264.7 macrophages. Results showed that the generation of RS from arachidonic acid through the COX-2 and XOD pathways was effectively suppressed by DHA and EPA, while GSH levels and antioxidative enzyme activities were significantly enhanced by DHA and EPA. Furthermore, levels of inflammatory mediators (thromboxane B2, PGE2, and 6-keto-PGF1alpha) and nitrite were effectively down-regulated by DHA and EPA. These results strongly indicate that DHA and EPA exert antioxidative and anti-inflammatory actions by reducing the cellular levels of RS, pro-inflammatory mediators, and nitrite levels and by maintaining higher GSH levels and antioxidative enzyme activities.
Kim
You Jung
YJ
Department of Cosmetology, Pusan Women's College, Busan, Republic of Korea.
Chung
Hae Young
HY
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000032:analysis; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects; D005978:Glutathione / Q000032:analysis; D007684:Kidney Tubules / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D009573:Nitrites / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013929:Thromboxane B2 / Q000032:analysis; D014969:Xanthine Oxidase / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D009573:Nitrites; D017382:Reactive Oxygen Species; D004281:Docosahexaenoic Acids; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015118:Eicosapentaenoic Acid; D051546:Cyclooxygenase 2; D014969:Xanthine Oxidase; D005978:Glutathione; D015232:Dinoprostone