The Role Of Hydrogen Sulfide In A Mouse Model Of Ozone-induced Oxidative Stress

Background and Objective Exposure to ozone is associated with airway inflammation, airway epithelial cell damage, oxidative stress and airway hyperresponsiveness( AHR). Hydrogen sulfide(H2S), as a newly discovered signaling gasotransmitter, may play an important role in the inflammatory and oxidative stress response. Endogenous H2 S is generated mainly by two enzymes, cystathionine-γ-lyase(CSE) and cystathionine-β-synthetase(CBS). The aim of this study was to investigate whether these adverse effects of ozone can be prevented by H2 S.Methods The mice were randomly divided into air exposed groups and ozone-exposed(3ppm for 3 hours) groups. Before each exposure, the mice were given intraperitoneal injection of sodium hydrosulfide(Na HS, H2 S donor) or propargylglycine(PPG, inhibitor of CSE, an H2S-synthesizing enzyme) and studied 24 hours later. The control group received phosphate buffered saline(PBS). In another in vitro study,we examined the modulating action of Na HS on large-conductance calcium activated K+channels BK channels(BKCa) from mouse airway smooth muscle cells using patch clamp techniques.Results Acute ozone exposure downregulated the H2S/CSE, CBS system. Ozone exposure decreased serum levels of H2 S, as well as the expression of CBS and CSE m RNA and protein. Exogenous H2 S donor Na HS ameliorated ozone-induced AHR, airway inflammation, oxidative stress, airway epithelial cell apoptosis, and downregulation of H2S/CSE, CBS system. Moreover, Na HS inhibited the phosphorylation of p38 mitogen-activated protein kinase(p38 MAPK) and heat shock protein 27(HSP27), but Na HS increased Akt( also known as protein kinase B) phosphorylation. However, blocking endogenous CSE with PPG reduced the level of endogenous H2 S, and aggravated lung tissue damage induced by ozone. In vitro experiments showed that Na HS increased Ca2+-dependent potassium outward currents of airway smooth muscle cells.Conclusions The results indicate that Na HS protects against ozone-induced oxidative stress. The protective effect is attributable to inhibition of p38 MAPK/HSP-27 pathway, and activation of Akt. In addition, H2 S increases BKCa channel of airway smooth muscle cells. H2 S may be of potential therapeutic value in the treatment of airway inflammatory diseases that have an oxidative stress basis.