ORIGINAL ABSTRACT

This study investigated the immunomodulatory effects of PFOS and glyphosate (GLY), both individually and in combination, on the whole blood of three ruminant species (cow, goats, and sheep) exposed ex vivo to environmentally relevant concentrations. The research focused on key biomarkers of oxidative stress (MDA), inflammation (myeloperoxidase activity, nitrite production), and immune function (TNFα and IL-6 cytokine production, both at baseline and following LPS stimulation). Results indicated species-specific differences in oxidative stress response, with sheep and goats showing higher MDA levels under combined PFOS and GLY exposure. Furthermore, co-exposure exacerbated inflammatory responses (MDA activity and NO2- production) in LPS-stimulated sheep and goats. Critically, a synergistic effect of PFOS and GLY co-exposure significantly increased both TNFα and IL-6 production across all species, even without LPS stimulation, suggesting a heightened pro-inflammatory state. These findings raise concerns about the potential of these contaminants to disrupt immune homeostasis in grazing animals, impacting their health, productivity, and disease resistance, and potentially posing risks to human health through food chain contamination. The study highlights the need for further research to elucidate the underlying molecular mechanisms and assess the long-term effects of chronic exposure to these contaminants on animal health and potential human health risks.