Cadmium affects osmotic phase and regulatory volume decrease in cultured human embryonic kidney cells

The present investigation aims to verify whether cadmium (Cd²⁺), a metal possibly accumulated in body tissues from air and food, affects cell volume regulation capability in cultured human embryonic kidney (HEK 293 Phoenix) cells. The osmotic phase (OP), which is the expected cell swelling due to aquaporins involvement after hyposmotic challenge, and regulatory volume decrease (RVD), bringing cell volume back to control values through Ca²⁺-dependent ion efflux (K+ and Cl–), have been monitored in HEK 293 cells treated with Cd²⁺ (1-10-100 μM) for different time intervals (30 min, 3 h, overnight) and then submitted to 15 % hyposmotic shock. The results show that both 1 and 10 μM Cd²⁺ significantly reduced OP, whereas 100 μM impaired Cd²⁺ RVD mechanisms. The use of glutathione (GSH, 200 μM) confirmed that Cd²⁺ elicited its effect via oxidative damage, being RVD inhibition after Cd²⁺ treatment prevented by this antioxidant compound. Our findings show that: i) HEK 293 cells are a suitable model to assay the effect of xenobiotics on cell homeostasis; ii) Cd²⁺, depending on its concentration, affects cell homeostasis at different levels, i.e. water and ion permeability, responsible for, respectively, OP and RVD mechanism, adding thus more information to the knowledge of Cd²⁺ toxicology.