Effects of Docosahexaenoic Acid (DHA) on oxidative stress parameters, inflammation, and resolvin D1 expression in a mouse model of neuroinflammation

Background: Neuroinflammation is a defense mechanism of the central nervous system against injury, involving the activation of glial cells and the release of pro-inflammatory mediators. When prolonged or excessive, this response can contribute to neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis, and anxio-depressive disorders. Docosahexaenoic acid (DHA), the main omega-3 fatty acid in the brain, is the precursor of specialized pro-resolving mediators (SPMs), including resolvin D1 (RvD1). However, its capacity to modulate RvD1 production in the context of neuroinflammation remains poorly documented.Aim and Objectives: To evaluate the effect of DHA supplementation on oxidative stress and inflammatory parameters, as well as on RvD1 expression, in a murine model of neuroinflammation.Materials and Methods: Thirty male BALB/c mice (11.7 – 30.2 g) were divided into three groups of 10 mice each: control (H2O); LPS (500 µg/kg, i.p., 7 days); and LPS+DHA (55 mg/kg, orally). Neuroinflammation was induced by intraperitoneal administration of lipopolysaccharide (LPS, 500 µg/kg, 7 days). Animals were then treated with DHA (55 mg/kg, orally) for 7 days. Twenty-four hours after the last treatment, blood samples were collected, after which the animals were sacrificed and the brains removed. Oxidative stress parameters (NO, nNOS, MDA, SOD, GPx) and inflammatory parameters (TNF-α, IL-1β, IL-6, IL-10), as well as RvD1 levels, were measured in serum and brain homogenates by ELISA.Results: DHA restored serum GPx activity (45.08 µmol/mL) and reduced serum SOD activity, NO levels, and nNOS expression, as well as brain MDA levels (14.8 µmol/mg). It increased brain RvD1 concentrations (from 786 to 2880 pg/mg, p = 0.04) and serum RvD1 concentrations (from 1046 pg/mL to 3710 pg/mL, p ≤ 0.0001).Conclusion: Our results suggest that DHA supplementation significantly attenuates brain oxidative stress and stimulates RvD1 production.