Impact of per- and polyfluoroalkyl substances structure on oxidative stress and lipid metabolism disruption in HepG2 Cells

Area of Science:

• Environmental toxicology
• Cell biology
• Metabolomics

Background:

• Per- and polyfluoroalkyl substances (PFASs) are persistent pollutants linked to ecosystem and human health risks.
• Oxidative stress and lipid metabolism disorders are key mechanisms in PFAS-induced liver toxicity.
• Understanding the differential toxicity of various PFASs based on chain length and functional groups is crucial.

Purpose of the Study:

• To investigate the cytotoxicity of different PFASs in HepG2 cells.
• To elucidate the mechanisms underlying PFAS hepatotoxicity, focusing on oxidative stress and lipid metabolism.
• To compare the toxicity of long-chain versus short-chain and carboxylate versus sulfonate PFASs.

Main Methods:

• HepG2 cells were exposed to varying concentrations of PFOA, PFOS, PFBA, and PFBS.
• Cytotoxicity was assessed by measuring cell viability.
• Oxidative stress markers (ROS, MDA), lipid metabolism (metabolomics, TG content), and related gene expression were analyzed.

Main Results:

• All tested PFASs reduced cell viability in a dose-dependent manner.
• Long-chain PFASs (PFOA, PFOS) induced significant oxidative stress and lipid accumulation.
• Metabolomics revealed substantial disruption of lipid metabolism, correlating with reduced cell viability.
• Long-chain and sulfonate PFASs exhibited higher toxicity than short-chain and carboxylate PFASs, respectively.

Conclusions:

• PFASs exert toxicity by exacerbating oxidative stress and lipid accumulation via lipid metabolism disorders.
• Differential toxicity exists among PFASs, with long-chain and sulfonate compounds being more potent.
• Findings provide a basis for enhanced risk assessment and management of PFAS exposure.