Hydrogen sulfide alleviates beryllium sulfate‐induced ferroptosis and ferritinophagy in 16HBE cells

Abstract Beryllium sulfate (BeSO 4 ) can result to lung injuries, such as leading to lipid peroxidation and autophagy, and the treatment of beryllium disease has not been well improved. Ferroptosis is a regulated cell death process driven by iron‐dependent and lipid peroxidation, while ferritinophagy is a process mediated by nuclear receptor coactivator 4 (NCOA4), combined with ferritin heavy chain 1 (FTH1) degradation and release Fe 2+ , which regulated intracellular iron metabolism and ferroptosis. Hydrogen sulfide (H 2 S) has the effects of antioxidant, antiautophagy, and antiferroptosis. This study aimed to investigate the effect of H 2 S on BeSO 4 ‐induced ferroptosis and ferritinophagy in 16HBE cells and the underlying mechanism. In this study, BeSO 4 ‐induced 16HBE cell injury model was established based on cellular level and pretreated with deferoxamine (DFO, a ferroptosis inhibitor), sodium hydrosulfide (NaHS, a H 2 S donor), or NCOA4 siRNA and, subsequently, performed to detect the levels of lipid peroxidation and Fe 2+ and the biomarkers of ferroptosis and ferritinophagy. More importantly, our research found that DFO, NaHS, or NCOA4 siRNA alleviated BeSO 4 ‐induced ferroptosis and ferritinophagy by decreasing the accumulation of Fe 2+ and lipid peroxides. Furthermore, the relationship between ferroptosis, ferritinophagy, H 2 S, and beryllium disease is not well defined; therefore, our research is innovative. Overall, our results provided a new theoretical basis for the prevention and treatment of beryllium disease and suggested that the application of H 2 S, blocking ferroptosis, and ferritinophagy may be a potential therapeutic direction for the prevention and treatment of beryllium disease.