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

Beryllium sulfate (BeSO 4 ) can result the 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, anti-autophagy and anti-ferroptosis. 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; 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.