Induction of oxidative stress and the associated lipid peroxidation is a prevalent mechanism through which certain metal(loid)s exert nephrotoxic effects in mammals. Research on the toxic impacts of metal(loid)s in free-ranging large mammals at high trophic positions is exceedingly rare, yet crucial for understanding environmental exposure scenarios relevant to both human and animal risk assessment. Renal cortex tissues (N=457) of free-ranging brown bears (Ursus arctos) from the Dinara-Pindos population sampled in Croatia were analysed herein for toxic metal(loid)s and the underlying biological and environmental drivers of variation, with their time trend monitored during the 2009-2022 period. In 28 individuals from the 2021-2022 period, we additionally investigated associations between metal(loid)s and oxidative stress and damage biomarkers in renal cortex cells. The principal generalized linear models used to approximate variations in biomarkers of oxidative stress and damage included non-essential As, Cd, Pb, Tl and U, and essential Co, Cu, Fe and Zn. Age class and season of sampling had no impact on biomarker levels, except for lipid peroxidation, LP (April ↑). Age, sex (females ↑), body condition index (↓) and season of sampling significantly influenced metal(loid)s levels. Non-specific mammalian thresholds were crossed for Cd and Pb toxicity in 1-16% and 2% of population, respectively. Renal levels of metal(loid) did not exhibit a clear trend over the 13-year period. The levels found in this study were higher than in sympatric carnivorous and herbivorous species, but in line with findings in ursids worldwide. Potential adverse health effects from environmental exposure in brown bears may arise from disruption of oxidative balance, as evidence clearly indicated associated changes in catalase activity (↑), glutathione content (↑), LP (↓), reactive oxygen species (↓), total antioxidant capacity (↑) in the renal cortex due to the presence of the most toxicologically relevant Cd and Pb.
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