AUTHOR=Pacchini Sara , Drago Laura , Cortese Martina , Vanzan Giacomo , Piva Elisabetta , Kholdihaghighi Shaghayegh , Barbarossa Andrea , Bardhi Anisa , Schumann Sophia , Fogliano Chiara , Bottacin-Busolin Andrea , Irato Paola , Marion Andrea , Santovito Gianfranco TITLE=From genes to organs: physiological responses of European chub (Squalius cephalus) to chronic PFAS pollution JOURNAL=Frontiers in Toxicology VOLUME=Volume 7 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/toxicology/articles/10.3389/ftox.2025.1654272 DOI=10.3389/ftox.2025.1654272 ISSN=2673-3080 ABSTRACT=Per- and polyfluoroalkyl substances (PFAS) are widespread anthropogenic contaminants known to the scientific community for their persistence and toxicity. Our research aims to evaluate the effect of chronic environmental exposure to PFAS on the antioxidant system of Squalius cephalus. In particular, to better understand how various components of the antioxidant system act together to counteract the adverse effects of PFAS, in the present study we evaluate the gene expression and enzymatic activity of two selenium-dependent glutathione peroxidases (namely GPx-1 and GPx-4) and the catalase, in the two major organs involved in the accumulation and detoxification from pollutants, including PFAS, i.e. liver and caudal kidney. Fish were sampled from four sites in the Veneto region with different concentrations of total dissolved PFAS. To better assess the acclimatisation to the environment, the morphological characteristics of the fish were also examined, as well as the development of organs, through the calculation of some somatic indices. Lipid accumulation was demonstrated histologically in both the liver and caudal kidney, which likely occurs to attenuate the high reactivity of PFAS toward protein content in these organs. The results demonstrate how Squalius cephalus can survive chronic PFAS exposure through cellular and systemic physiological responses.