Environmentally Relevant Concentrations of Propofol-Induced Metabolic Dysfunction in Zebrafish: Mechanistic Insights into Integrated Hepatic Transcriptomic and Metabolomic Analyses

Propofol is increasingly perceived as an emerging threat to aquatic ecosystems, although the ecotoxicity and underlying mechanisms of propofol on aquatic life have not yet been clearly established. In this study, zebrafish (Danio rerio) was exposed to different concentrations of propofol (0.008, 0.04, and 0.2 mg·L–1) to probe the effect of propofol on functional metabolism and the ecological response mechanism in aquatic organisms. Propofol induced severe hepatic damage, including increased interstitial spaces and nuclear malformations at the tissue level. Reactive oxygen species (ROS) production and lipid peroxidation in zebrafish were induced after 28 days of exposure, while the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were substantially increased, suggesting that propofol may influence hepatic tissue injury through exacerbating oxidative damage. Exacerbated levels of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) were indicative of dysregulated lipid metabolism. Comprehensive transcriptomics and metabolomics analyses showed that propofol mainly changed the glycerophospholipid metabolism, citric acid cycle, and purine metabolism, and the disorders of these pathways can aggravate lipid accumulation and oxidative damage. Overall, this study revealed the mechanisms of hepatotoxicity and metabolic dysfunction of propofol on zebrafish, providing constructive insights for a comprehensive assessment of the toxicity risk posed by propofol to aquatic environmental health.