087 | Synergistic collapse of redox homeostasis in human hepatic and renal cells: perfluorooctane sulfonate as a priming factor for oxidative pathophysiology

Graziano Vinci¹, Marika Cordaro², Rosanna Di Paola³ | ¹Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina, Italy; ²Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Italy; ³Department of Veterinary Sciences, University of Messina, Italy.

Endocrine disruptors (EDs) have emerged as a major public health concern due to their ability to interfere with hormonal regulation and disrupt metabolic, reproductive, and developmental processes. These compounds are now pervasive in the environment and frequently detected in air, water, and soil, where they can bioaccumulate in living organisms. Among them, perfluorooctane sulfonate (PFOS) is one of the most extensively studied due to its extensive industrial and commercial applications. In addition, the chemical stability makes PFOS contribute to its environmental persistence and bioaccumulation potential. Despite substantial environmental monitoring data, the molecular and cellular effects of PFOS remain insufficiently understood. Its impact on human cell models representing key target organs, such as kidney (HEK293) and liver (HepG2) cells, could be better characterized. The present study aimed to investigate the cellular response to PFOS exposure (200 µM) in these two human-derived cell lines. We evaluated the compound’s ability to induce oxidative stress by measuring reactive oxygen species (ROS) generation, as well as its capacity to modulate pro-inflammatory cytokines, including IL-6, TNF, and IL-10. Our findings reveal that PFOS alone, at non-cytotoxic concentrations, does not produce significant oxidative or inflammatory effects. However, co-exposure with hydrogen peroxide (300 µM) markedly enhanced ROS production and upregulated pro-inflammatory mediators, suggesting a synergistic effect that amplifies cellular stress responses. These results underscore the importance of assessing combined chemical exposures when evaluating the toxicological potential of EDs.