A subcellular study on reactive oxygen species generation by PFAS in HepG2 cells

Area of Science:

• Environmental toxicology
• Cellular biology
• Biochemistry

Background:

• Per- and polyfluoroalkyl substances (PFAS) are linked to liver toxicity, but mechanisms remain unclear.
• Understanding PFAS-induced reactive oxygen species (ROS) formation is crucial for assessing hepatotoxicity.

Purpose of the Study:

• Investigate the origin of PFAS-induced ROS and their role in HepG2 cell viability.
• Assess structure-activity relationships of PFASs based on headgroup and carbon-chain length.
• Determine the involvement of mitochondria and peroxisomes in PFAS-induced ROS generation.

Main Methods:

• Exposed HepG2 cells to various PFASs with different headgroups and chain lengths.
• Utilized quercetin and mito-tempo antioxidants to assess ROS links to cell viability.
• Measured peroxisomal and mitochondrial activity, lysosomal leakage, and lipid peroxidation.

Main Results:

• PFAS exposure increased ROS generation and decreased HepG2 cell viability.
• Both quercetin and mito-tempo reduced PFAS-induced ROS, but only quercetin improved cell viability after PFCA and PFSA exposure.
• PFASs did not affect peroxisomal or mitochondrial activity within 24 hours; lysosomal leakage and lipid peroxidation were secondary effects.
• PFOA and PFOS exposure reduced catalase activity, suggesting endogenous antioxidant inhibition.

Conclusions:

• PFAS-induced ROS generation may stem from inhibiting endogenous antioxidants in HepG2 cells.
• A headgroup-dependent mechanism is implicated, with perfluoroalkyl carboxylic acids (PFCAs) and perfluorosulfonic acids (PFSAs) potentially causing hepatotoxicity via different pathways.