Submicron Particulate Matter (PM1)-Induced Pulmonary Injury and Epigallocatechin-3-Gallate Intervention: Modulation of Disorders in Amino Acid, Glycerophospholipid, and Energy Metabolism.

Emerging evidence indicates that submicron particulate matter (PM1) poses greater respiratory health risks than coarser particles (e.g., PM2.5). Yet its specific toxicological mechanisms and effective mitigation strategies remain insufficiently understood. This study demonstrated that PM1 exposure induced significant dose-dependent pulmonary oxidative stress and inflammatory response in vivo and in vitro. Metabolomic analysis revealed that PM1 triggered more complex metabolic alterations than those induced by PM2.5, including disorders in amino acid metabolism, glycerophospholipid metabolism, and energy metabolism. A notable hormesis-like effect was observed in energy metabolism, where fatty acid β-oxidation was stimulated at a low dose but inhibited at high doses. It was also found that ten metabolites strongly correlated with the severity of oxidative stress and inflammatory response as potential biomarkers. Furthermore, both in vivo and in vitro experiments confirmed that epigallocatechin-3-gallate (EGCG) intervention effectively alleviated PM1-induced lung injury by restoring redox balance, suppressing inflammatory responses, and modulating the metabolic disorders. Our findings not only provided a new insight into the underlying mechanism of PM1 toxicity, advocating for enhanced regulatory attention and risk assessment specifically targeted at PM1, but also highlighted the potential of EGCG as a promising nutritional intervention against the adverse health effects of PM1 exposure.