Elovanoids Suppress Lipid Peroxidation after Experimental Stroke: An LC-MS-based Untargeted Lipidomics Analysis

Abstract

At the onset and progression of neurodegenerative diseases, enhanced reactive oxygen species (ROS) and an overall uncompensated oxidative stress environment evolve. Oxidized phospholipids (OxPLs) cause detrimental perturbations to synaptic membranes and other parts of the nervous system. We tested if the lipid mediators Elovanoids (ELVs) that exert neuroprotective signaling also counteract lipid peroxidation using an experimental ischemic stroke model. Male Sprague-Dawley rats after 2 hours of middle cerebral artery occlusion (MCAo) were used. ELV-N34 was administered intranasally at 1 hour, 24 hours and 48 hours after, and rats were sacrificed on day 3; the brains were removed and sampled into the right and left hemispheres and the cortex, subcortex. Untargeted lipidomics were performed using a Waters Xevo G2-XS QTof system under MSE mode, and collected MS/MS spectra for the OxPLs was processed and searched against a reference spectral library by MS-DIAL software. ELV-N34 reduced oxidized phosphatidylcholine (OxPC) and phosphatidylethanolamine (OxPE) molecular species. We suggest that ELVs target lipid peroxidation as part of their neuroprotective bioactivity.