Mechanistic Insights into Cadmium Sulfide Nanoparticles-Induced Digestive Gland Damage in <i>Corbicula fluminea</i>: Comparison with Cadmium Ions

The extensive use of cadmium sulfide nanoparticles (CdS-NPs), along with their natural formation through the complex biogeochemical transformation of anthropogenic cadmium ions (Cd²⁺), poses substantial risks to ecosystems and human health. Despite this, the mechanisms underlying the toxicity of CdS-NPs remain unclear. A key question is whether their toxicity arises from the nanoparticulate form of cadmium (Cd) or from the release of Cd²⁺. To explore this, we exposed freshwater clams <i>(Corbicula fluminea)</i> to environmentally relevant concentrations (0.01-1 mg/L) of CdS-NPs or Cd²⁺ for 10 days. Hematoxylin and eosin (HE) staining revealed significant damage to the digestive gland in both cases. Although CdS-NPs released some Cd²⁺ (≤10.4%), transcriptomic and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses indicated different toxicity mechanisms. CdS-NPs primarily induce ferroptosis, triggered by lysosomal dysfunction that releases Fe²⁺ into the cytoplasm, disrupting the cellular iron metabolism. In contrast, Cd²⁺ primarily induces an autophagic response, as evidenced by the upregulation of autophagy-related markers and activation of apoptosis pathways linked to mitochondrial membrane permeabilization. Overall, our findings suggest that the toxicity of CdS-NPs is not solely derived from Cd²⁺, highlighting the need to evaluate the risks posed by metal sulfide nanoparticles to benthic ecosystems.