Lipidomics Investigation Reveals the Reversibility of Hepatic Injury by Silica Nanoparticles in Rats After a 6‐Week Recovery Duration

Given the inevitable human exposure owing to its increasing production and utilization, the comprehensive safety evaluation of silica nanoparticles (SiNPs) has sparked concerns. Substantial evidence indicated liver damage by inhaled SiNPs. Notwithstanding, few reports focused on the persistence or reversibility of hepatic injuries, and the intricate molecular mechanisms involved remain limited. Here, rats are intratracheally instilled with SiNPs in two regimens (a 3‐month exposure and a subsequent 6‐week recovery after terminating SiNPs administration) to assess the hepatic effects. Nontargeted lipidomics revealed alterations in lipid metabolites as a contributor to the hepatic response and recovery effects of SiNPs. In line with the functional analysis of differential lipid metabolites, SiNPs activated oxidative stress, and induced lipid peroxidation and lipid deposition in the liver, as evidenced by the elevated hepatic levels of ROS, MDA, TC, and TG. Of note, these indicators showed great improvements after a 6‐week recovery, even returning to the control levels. According to the correlation, ROC curve, and SEM analysis, 11 lipids identified as potential regulatory molecules for ameliorating liver injury by SiNPs. Collectively, the work first revealed the reversibility of SiNP‐elicited hepatotoxicity from the perspective of lipidomics and offered valuable laboratory evidence and therapeutic strategy to facilitate nanosafety. SiNPs are frequently encountered in the environment, and the liver is vital to SiNPs accumulation and removal after introduction into the body. Here, subchronic exposure to SiNPs induces hepatic oxidative stress and lipid deposition. Nevertheless, these phenomena are greatly alleviated when rats are given a 6‐week recovery. Lipidomics analysis reveals 11 lipids as potential mediators to ameliorate liver injury by SiNPs.