Comprehensive multi-omics approaches reveal the hepatotoxic mechanism of perfluorohexanoic acid (PFHxA) in mice

Perfluorohexanoic acid (PFHxA), one of the short-chain perfluoroalkyl acids (PFAAs), is considered as a substitute of perfluorooctane sulfonate (PFOS). This emerging organic pollutant is persistent and highly bioavailable to humans, raising concerns about its potential health risks. There are currently few researches on the toxicity of PFHxA. Liver has been suggested to be the main target of PFHxA toxicity, and the mechanism remains unclear. Herein, we investigated the transcriptomic, proteomic, and metabolomic landscape in PFHxA-exposed mice. Using these approaches, we identified several valuable biological processes involved in the process of liver injury, comprising fatty acid biosynthesis and degradation pathways, which might be induced by peroxisome proliferator-activated receptor (PPAR) signaling pathway. These processes further promoted oxidative stress and induced liver injury. Meanwhile, abnormalities in purine metabolism and glutathione metabolism were observed during the liver injury induced by PFHxA, indicating the production of oxidative stress. Finally, our present multi-omics studies provided new insights into the mechanisms involved in PFHxA-induced liver injury.