Diltiazem disrupts Ca2+-homeostasis and exerts immunotoxic effects on a marine bivalve mollusc, the blood clam (Tegillarca granosa).

The prevalence of pharmaceutical residues like diltiazem in environments raises concerns over their potential threat to non-target organisms. While the immune system poses as a potential target, little is known about the immunotoxicity of diltiazem to aquatic species such as bivalve molluscs. In this study, the binding affinity of diltiazem to the calcium channels of several aquatic species was evaluated by molecular docking. Taking blood clam as a representative, the impacts of diltiazem on Ca2+-homeostasis and immune parameters were also assessed. Our results illustrated diltiazem exhibit a high binding affinity to calcium channels of representative aquatic species. Moreover, Ca2+-homeostasis in the haemocytes of blood clam was significantly disrupted by 4-week exposure to diltiazem. Additionally, apart from exhibiting significantly lower survival rates upon pathogenic challenge, diltiazem-exposed blood clams also suffered markedly impaired immune-related hematic parameters and lower levels of immune factors. Furthermore, diltiazem exposure generally altered the expression of key Ca2+-homeostasis and immune-related genes. Collectively, our data suggest that diltiazem at environmentally relevant concentrations could severely undermine the immunity of blood clam by disrupting Ca2+-homeostasis. Given the high binding affinities of diltiazem to calcium channels of diverse aquatic species and the critical role of Ca2+-homeostasis, the far-reaching impacts of diltiazem pollution on non-target aquatic species warrant closer attention and monitoring.