Selenite protects human peripheral blood mononuclear cells (PBMCs) from CdCl₂ cytotoxicity

The potential role of selenium (Se) in modulating cadmium (Cd) cytotoxicity in human peripheral blood mononuclear cells (PBMCs) was investigated by assessing pro- and anti-inflammatory as well as redox biomarkers. We also examined the potential synergistic effects of SARS-CoV-2 N-protein with Cd in PBMCs. PBMCs were isolated from adults and treated for 48 h with sodium selenite (Na₂SeO₃; 0.04, 0.4, and 4 µM) and cadmium chloride (CdCl₂; 0.1 and 1 µM), in the presence or absence of SARS-CoV-2 N-protein. We measured total Se and Cd levels, cell viability, cytotoxicity, intracellular reactive oxygen species (ROS) production, and gene expression. Na₂SeO₃ antagonized CdCl₂-induced toxicity in PBMCs. This protective effect was associated with increased expression of antioxidant selenoprotein mRNAs, including GPX1, GPX4, TXNRD1, SELENOP, SELENOS, and SELENOK. Notably, even low concentrations of Na₂SeO₃ effectively protected PBMCs from Cd-induced toxicity, reversing cell death and restoring MTT reduction. Cd exposure slightly increased DCFH oxidation, which was abolished by Na₂SeO₃. While Cd did not markedly elevate ROS, it consistently increased inflammatory markers. Importantly, Na₂SeO₃ upregulated anti-inflammatory mRNAs (IL-4, IL-10), even in the presence of CdCl₂. These findings suggest that, regardless of SARS-CoV-2 N-protein presence, sufficient Se levels-and consequently, proper selenoprotein expression-are crucial for modulating inflammation, preventing ROS overproduction, and mitigating oxidative stress in human PBMCs.