Protective effects of lipid mediators, obtained from docosahexaenoic acid via soybean lipoxygenase, on lipopolysaccharide‑induced acute lung injury through the NF‑κB and Nrf2/HO‑1 signaling pathways

Acute lung injury (ALI), marked by acute and chronic inflammation, causes damage to alveolar epithelial and capillary endothelial cells. The present study investigated lipid mediators (LM) effects on lipopolysaccharide (LPS)‑induced RAW264.7 cells and ALI mice. LM, comprising 17S‑monohydroxy docosahexaenoic acid (DHA), resolvin D5 and protectin DX (in a 3:47:50 ratio), were derived from DHA via soybean Lipoxygenase and demonstrated anti‑inflammatory properties. In vitro experiments revealed that LM decreased nitric oxide (NO) and prostaglandin E2 (PGE2) levels caused by LPS via downregulating inducible nitric oxide synthase and cyclooxygenase‑2. Additionally, LM inhibited the inflammation by suppressing NF‑κB signaling. The results also indicated that LM reduced oxidative stress by lowering Reactive Oxygen Species and malondialdehyde (MDA) levels while enhancing glutathione (GSH) content and superoxide dismutase (SOD) activities, probably through activation of nuclear factor erythroid 2‑related factor 2 (Nrf2)/heme oxygenase‑1 (HO‑1) signaling pathway. Moreover, the benefits of LM on inflammation and oxidative stress were reversed when pretreated with ML385, an Nrf2 inhibitor. In vivo studies revealed that LM reduced the lung wet/dry ratio, increased GSH, catalase and SOD activities, along with lowered myeloperoxidase and MDA levels. In addition, LM reduced inflammatory cytokine levels in serum and bronchoalveolar lavage fluid. Mechanistically, LM inhibited NF‑κB signaling and activated Nrf2/HO‑1 signaling pathways.

NF‑κB; acute lung injury; inflammation; nuclear factor erythroid 2‑related factor 2/heme oxygenase‑1; oxidative stress.