Identification of biochemical targets of rare earth elements in bivalve mollusks under combined exposure conditions

Rare earth elements (REE) are considered the pollutants of priority, and biological effects are studied poorly. Aim. Our study was devoted to the elucidation of suspected biochemical effects of two representative REEs, gadolinium (Gd) and yttrium (Y), individually and in a mixture with Ca-channel blocker nifedipine (Nfd), using the freshwater bivalve Unio tumidus as a model organism. Materials and Methods. The specimens of swollen river mussel Unio tumidus were treated with GdCl3, 30 nM, YCl3, 30 nM, or their mixture with Nfd (10 μM) for 14 days. The set of metal-binding, reductive state, biotransformation activities, and toxicity in the digestive gland of mussels was selected. Results. All exposures caused the elevation of the ratio of reduced and oxidized forms of nicotinamide adenine dinucleotide (NADH/NAD+ ratio) and increase of the levels of reduced and oxidized glutathione (GSH and GSSG), the total level of cysteine-rich protein metallothionein (MTSH) in the Gd- and Y- groups and non-metalated MTSH in all exposures. The effects on the transformation of Phase I and Phase II enzymes were exposure-dependent. Dynamin-related GTP-ase activity increased in all exposures. The lysosomal membrane integrity and apoptotic activity decreased only in the Gd-group. Conclusion. REEs in low concentrations cause adaptive metabolic responses in the mussels. The changes in the Zn distribution within the cells and Zn-dependent functions were indicated, confirming the impact of REEs on the functionality of the essential metal. In the combined exposure of REEs with a Ca-channel blocker, a cumulative effect was detected.