Multilevel Screening Strategy to Identify the Hydrophobic Organic Components of Ambient PM_2.5 Associated with Hepatocellular Steatosis

Abstract

Hepatic steatosis is the first step in a series of events that drives hepatic disease and has been considerably associated with exposure to fine particulate matter (PM 2.5 ). Although the chemical constituents of particles matter in the negative health effects, the specific components of PM 2.5 that trigger hepatic steatosis remain unclear. New strategies prioritizing the identification of the key components with the highest potential to cause adverse effects among the numerous components of PM 2.5 are needed. Herein, we established a high-resolution mass spectrometry (MS) data set comprising the hydrophobic organic components corresponding to 67 PM 2.5 samples in total from Taiyuan and Guangzhou, two representative cities in North and South China, respectively. The lipid accumulation bioeffect profiles of the above samples were also obtained. Considerable hepatocyte lipid accumulation was observed in most PM 2.5 extracts. Subsequently, 40 of 695 components were initially screened through machine learning-assisted data filtering based on an integrated bioassay with MS data. Next, nine compounds were further selected as candidates contributing to hepatocellular steatosis based on absorption, distribution, metabolism, and excretion evaluation and molecular dockingin silico. Finally, seven components were confirmed in vitro. This study provided a multilevel screening strategy for key active components in PM 2.5 and provided insight into the hydrophobic PM 2.5 components that induce hepatocellular steatosis.