LC-MS/MS Evaluation of Lipid Oxidation Mechanisms: Antioxidant Strategies for Health

Lipid oxidation stress has been an area of interest because of its involvement in various diseases. Recently, we developed a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to analyze lipid hydroperoxide (LOOH) isomers, the primary oxidation products of lipids.

LOOH is formed by the oxidation of unsaturated fatty acids that constitute lipids. Importantly oxidation takes place at different positions within the lipid structure (i.e., hydroperoxyl groups are introduced at different positions) depending on oxidation mechanisms (i.e., enzymatic oxidation, radical oxidation, or singlet oxygen oxidation). Our LC-MS/MS method, by utilizing sodium ions, can induce position-specific fragmentation of the hydroperoxide group of LOOH. Thus, the position of the hydroperoxide group can be accurately determined, and lipid oxidation mechanisms can be evaluated. Such identification of oxidation mechanisms would allow for the efficient prevention of lipid oxidation stress via selection of antioxidants that effectively prevent each oxidation mechanism.

An example of our recent studies, using our LC-MS/MS method, we are currently investigating whether ferroptosis, a new type of cell death, is induced by radical oxidation-induced LOOH, as previous studies have hypothesized. We also participated in several collaborative studies on ferroptosis and discovered that some antioxidants effectively inhibit ferroptosis via its antioxidant properties that trap radicals.

 In this presentation, taking the analysis of phospholipid hydroperoxide (PLOOH) isomers as a specific example of LOOH, I will introduce our LC-MS/MS research on the elucidation of the mechanism of lipid oxidation and diseases (especially ferroptosis) and the antioxidant strategies for health. if time permits, I would also like to introduce the application of our LC-MS/MS method to the field of food research.