Hydrogen Sulfide Attenuates Hydrogen Peroxide-Induced Injury in Human Lung Epithelial A549 Cells

Lung tissues are frequently exposed to a hyperoxia environment, which leads to oxidative stress injuries. Hydrogen sulfide (H₂S) is widely implicated in physiological and pathological processes and its antioxidant effect has attracted much attention. Therefore, in this study, we used hydrogen peroxide (H₂O₂) as an oxidative damage model to investigate the protective mechanism of H₂S in lung injury. Cell death induced by H₂O₂ treatment could be significantly attenuated by the pre-treatment of H₂S, resulting in a decrease in the Bax/Bcl-2 ratio and the inhibition of caspase-3 activity in human lung epithelial cell line A549 cells. Additionally, the results showed that H₂S decreased reactive oxygen species (ROS), as well as neutralized the damaging effects of H₂O₂ in mitochondria energy-producing and cell metabolism. Pre-treatment of H₂S also decreased H₂O₂-induced suppression of endogenous H₂S production enzymes, cystathionine-beta-synthase (CBS), cystathionine-gamma-lyase (CSE), and 3-mercapto-pyruvate sulfurtransferase (MPST). Furthermore, the administration of H₂S attenuated [Ca²⁺] overload and endoplasmic reticulum (ER) stress through the mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, H₂S might be a potential therapeutic agent for reducing ROS and ER stress-associated apoptosis against H₂O₂-induced lung injury.