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Cypermethrin and perfluorooctane sulfonate co-exposure: Synergistic immunotoxicity in ex vivo stimulated whole blood of Nile tilapia ( Oreochromis niloticus )

2026/05/04 by Regina Aparo, Sabrina Natale, Carmelo Iaria +4

paper · doi:10.1093/etojnl/vgag114

Abstract

Abstract Environmental contaminants pose an increasing threat to aquatic organisms, with potential consequences for fish health, aquaculture, and food safety. This study investigated the cytotoxic and immunotoxic effects of perfluorooctane sulfonate (PFOS) and the synthetic pyrethroid cypermethrin (CYP) in Nile tilapia (Oreochromis niloticus) using ex vivo peripheral blood mononuclear cell (PBMC) cultures and whole blood assays. High concentrations of PFOS and CYP reduced PBMC viability in a concentration and time-dependent manner, with CYP exhibiting stronger cytotoxicity. Reactive oxygen species-related oxidative burst and reverse transcriptase quantitative polymerase chain reaction analyses revealed that PFOS (10 μM) and CYP (1 μM) induced oxidative stress and modulated the expression of antioxidant catalase, superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and cytokine cytokines tumor necrosis factor-α, interleukin-1β, and transforming growth factor- β genes, indicating disruption of immune regulation. Importantly, co-exposure to subtoxic concentrations of PFOS (1 μM) and CYP (100 nM) elicited significant cytotoxic and immunotoxic responses, including reduced PBMC viability, increased myeloperoxidase and malondialdehyde levels, increased oxidative burst activity and nitrite production, and altered gene expression. These effects were comparable to those induced by lipopolysaccharide, a proinflammatory control, suggesting a potential interaction between the two contaminants. Although single exposures at these concentrations were largely inactive, the combined treatment revealed the enhanced toxic potential of chemical mixtures in aquatic environments. Overall, these findings emphasize the importance of evaluating combined exposures, as interactions between environmental contaminants may pose greater risks to fish health, aquaculture sustainability, and food safety than individual pollutants alone.

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