Cadmium induces the secretion of SASP factors regulated by MAPK and NF-κB signaling pathways in HEK293 cells: A possible mechanism of acute kidney damage induced by cadmium.

Cadmium (Cd) is a highly toxic environmental pollutant, which can accumulate in the kidney, induce cell damage and trigger inflammatory responses. However, the specific regulation mechanism of nephrotoxicity induced by Cd remains unclear. This study was conducted to investigate the toxic effects of Cd on human embryonic kidney 293 (HEK293) cells and explore its potential mechanisms. Cell viability was assessed with MTT assay. Reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were evaluated through DCFH-DA staining and Rhodamine staining. Apoptosis was detected with Hoechst 33258 staining. The expression of the DNA damage biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG) was detected with the 8-OHdG ELISA kit. Senescence-associated secretory phenotype (SASP) factors and signaling pathways were analyzed by Western blot. The results showed that Cd exposure could induce oxidative stress and cellular inflammation. It could also impair MMP, contribute to cell apoptosis and activate MAPK and NF-κB signaling pathways. Finally, exposure to Cd triggered DNA damage and SASP production. However, NF-κB inhibitor BAY11-7082 and antioxidant NAC could inhibit these effects by suppressing NF-κB and MAPK signaling pathways. The present study revealed the specific mechanisms of Cd toxicity in HEK293 cells and provided useful information for elucidating the nephrotoxicity of Cd.