2025 Volume 25 Issue 11 Pages 495-502
Ferroptosis is an iron-dependent form of regulated cell death characterized by excessive lipid peroxidation, and has been implicated in various human diseases and organ pathologies. However, assessment of lipid peroxidation has required invasive tissue sampling, rendering the noninvasive detection of ferroptosis in humans highly challenging.
In this study, we employed oxidative volatolomics to comprehensively analyze the volatile oxidized lipids (VOLs) generated during ferroptosis. VOLs derived from polyunsaturated fatty acids were produced through iron-dependent lipid peroxidation and released extracellularly as ferroptosis progressed. These VOLs were specifically generated during hepatic ferroptosis in mouse models of acetaminophen-induced liver injury and metabolic dysfunction-associated steatohepatitis metabolic dysfunction-associated steatohepatitis (MASH), and were further detectable in the exhaled breath of patients with MASH. Specific VOLs released via iron-dependent lipid peroxidation may serve as in vivo indicators of ferroptosis and hold promise as breath biomarkers for noninvasive monitoring of cellular health in humans.
