Using Volatile Oxidation Products to Predict the Inflammatory Capacity of Oxidized Methyl Linoleate

This study evaluated whether the volatile profile of methyl linoleate (MLO) can predict its pro-inflammatory capacity. MLO was subjected to two oxidation conditions simulating ambient storage and high-temperature frying. Free radicals, volatile compounds, and aldehydes were quantified using ESR, HS-SPME-GC-MS, and UPLC-MS/MS. Oxidized MLO was applied to RAW264.7 macrophages to evaluate inflammatory cytokines and oxidative stress responses, and PLSR models were developed to predict cellular outcomes based on volatile fingerprints. Both oxidation conditions induced substantial increases in short-chain and unsaturated aldehydes, with high-temperature oxidation generating markedly higher levels of key volatiles. Oxidized MLO significantly elevated TNF-α, IL-1β, COX-2, ROS, NO, and MDA while reducing SOD activity (p < 0.05), demonstrating strong pro-inflammatory and pro-oxidant effects. Volatile-based PLSR models achieved high predictive performance, with cross-validated and external R2 values approaching 0.9 and RPD values exceeding 2. These findings show that volatile oxidation products reliably reflect the pro-inflammatory potency of oxidized lipids and can support the ranking of oxidized oils and lipid-rich foods, as well as guide processing and dietary strategies.