Metabolomics-based investigation of PFOS-induced molecular perturbations across multiple rat organs

Abstract

This study aimed to investigate the perfluorooctane sulfonic acid (PFOS)-induced metabolic alterations in several organs and establish the potential mechanisms underlying the organ toxicity. A nuclear magnetic resonance-based metabolomics approach was employed to analyze metabolic alterations in multiple organs and serum of male rats exposed to varying doses of PFOS. We observed significant alterations in metabolites associated with inflammation (e.g., uridine diphosphate glucose), energy metabolism (e.g., adenosine monophosphate and adenosine triphosphate), amino acid (e.g., branched-chain amino acids), carbohydrate metabolism, and oxidative stress modulation (e.g., glutathione and taurine) in several organs. These alterations could be linked to inflammation, fibrosis, mitochondrial dysfunction, insulin resistance, and oxidative stress. Succinate accumulation was observed in the heart and liver, suggesting the susceptibility of these organs to mitochondrial dysfunction. Overall, our findings revealed potential key molecular events triggered by PFOS exposure, contributing to a deeper understanding of the possible adverse effects on multiple organs.