Hydrogen sulfide mitigates the immunotoxicity and neurotoxicity induced by cadmium in Tegillarca granosa

The blood clam Tegilarca granosa is an economically important shellfish in Asia. The complex living environment often exposes the clams to cadmium (Cd) and hydrogen sulfide (H₂S). H₂S is well-known for its toxic effects, however, it is still unclear whether it can participate in regulating the heavy metal adaptation in clams. Here, we subjected T. granosa to chronic Cd stress (50 μg/L, 14 days) to explore their physiological and molecular response patterns under the addition of 0.2, 0.4, and 0.8 mM H₂S. The results indicated that the Cd stress induced the immune-toxicity and neurotoxicity in the gills and viscera. H₂S could alleviate the toxicity by inducing phagocytosis rate, maintaining AChE and Ca^{2 +}- ATPase activities, reducing MDA and O₂^- contents, promoting the excretion or degradation of Cd, and inhibiting the Ca²⁺ signaling pathway (CaM, CaMK2, CaMKK2). However, high concentrations of H₂S also inhibited the ATPase activities and the apoptotic signaling pathway. Altogether, our results indicated that H₂S has a special regulatory mechanism for Cd toxicity in the clam T. granosa, and this regulation may depend on the Ca²⁺ signaling pathway. Our results would offer insights into the sulfide and Cd - tolerant molecular mechanisms in this species and provide a useful tool for assessing the integrated biological impacts of Cd and sulfide on shellfish.