Lipid mediators obtained from docosahexaenoic acid by soybean lipoxygenase alleviate ovalbumin-induced allergic asthma in mice by reducing airway inflammation and oxidative stress

Abstract

Asthma is a chronic allergic respiratory disease lacking effective therapies. The present study investigated the anti-asthmatic properties of lipid mediators using an ovalbumin (OVA)-induced allergic asthma model. Lipid mediators (LM; 17S-monohydroxy docosahexaenoic acid, resolvin D5 and protectin DX at a ratio of 3:47:50) were derived from docosahexaenoic acid through soybean lipoxygenase. LM treatment significantly alleviated major features of allergic asthma, including inflammatory cell infiltration, with a particular reduction in eosinophils in bronchoalveolar lavage fluid, downregulation of Th2 cytokine expression, attenuation of airway remodeling, and oxidative stress, thereby closely resembling the normal condition. Additionally, a significant increase in the serum levels of interleukin-6 [167.12 +/- 6.25 pg/ml; P<0.0001 vs. negative control (NC) group], tumor necrosis factor-alpha (109.17 +/- 7.17 pg/ml; P<0.0001 vs. NC group) and IgE (90.24 +/- 5.98 ng/ml; P<0.0001 vs. NC group) was observed following OVA challenge; however, oral administration of LM resulted in a notable reduction in these levels to 99.45 +/- 6.12 pg/ml (P<0.001 vs. OVA group), 62.51 +/- 4.03 pg/ml (P<0.001 vs. OVA group) and 56.50 +/- 2.70 ng/ml (P<0.001 vs. OVA group), respectively. Furthermore, the heightened expression of Th2-related cytokines induced by OVA was observed to be restored closely to normal conditions following LM treatment, as demonstrated for both gene and protein expression levels. Histological analysis demonstrated that LM mitigated inflammatory cell infiltration while reducing mucus secretion. Additionally, LM effectively ameliorated oxidative stress in OVA-induced asthma, with a significant increase in the activity of superoxide dismutase (similar to 185% vs. OVA group; P<0.001), elevated levels of glutathione (similar to 74% higher than the OVA group; P<0.001) and reduced content of malondialdehyde (similar to 40% lower than the OVA group; P<0.001) in lung tissues. Collectively, these findings suggested that LM effectively protected lung tissues from inflammation and oxidative stress, thereby representing a promising therapeutic option for the treatment of allergic asthma.