Environmentally relevant doses of gadolinium (GdCl3; Gd2O3) trigger immune and antioxidant effects in non-target organisms: Cellular and tissue responses in the gills of mussel Mytilus galloprovincialis

The current abundance of gadolinium (Gd) in aquatic ecosystems is attributable to its wide use in several fields ( i.e. metallurgy, electronic devices production), above all medical imaging and treatment. Various harmful effects of Gd have been largely documented on human cells, likely due to its chemical affinity with Ca 2+ . However, these effects are still poorly evaluated in aquatic organisms, especially invertebrates. Therefore, this work aims to unveil the impact of two forms of Gd (gadolinium chloride, GdCl 3 ; gadolinium oxide nanoparticles, Gd 2 O 3 ) on the gills of mussels Mytilus galloprovincialis , following exposure for 28 days to two environmental doses (1 μg/L; 10 μg/L) of GdCl 3 and Gd 2 O 3 , by investigating on tissue organization, antioxidant system, immune responses, energy metabolism, and neurotransmission system. Despite the lack of a relevant Gd bioaccumulation in mussel gills, after exposure to both Gd forms a marked haemocyte infiltration was observed in gill tissues at every exposure time-points (T7; T15; T28), suggesting a potential immune response involvement, further supported by an imbalance in mucopolysaccharide secretions and an enhancement in the alkaline phosphatase activity at T7. At T28, a disruption in the antioxidant system, evaluated by gene expression and enzymatic activity of the main antioxidant and detoxifying enzymes (GST, CAT, SOD), was reported, together with changes in lactate dehydrogenase (LDH) activity suggesting activation of anaerobic metabolism. Overall, this study highlights the ability of Gd to induce significant physiological disruptions even in the absence of substantial bioaccumulation, underscoring its potential ecological risk at environmentally relevant concentrations.