Hydrogen sulfide donors prevent lipopolysaccharide-induced airway hyperreactivity in an in vitro model of chronic inflammation in mice

We aimed to investigate and compare the effects of rapid (NaHS) and slow (GYY4137 and AP39) hydrogen sulfide (H2S) releasing donors on LPS-induced tracheal hyperreactivity and pro-inflammatory cytokine levels in lung tissues of mice. Tissues were isolated from male BALB/c mice and incubated with LPS (10 mu g/mL) in tissue culture. The subgroups were incubated with NaHS, GYY4137 and mitochondria-targeted donor AP39. LPS incubation did not alter contraction response to carbachol, but enhanced 5-HT and bradykinin-induced contractions in tracheal rings, and elevated IL-1 beta, IL-6 and TNF-alpha levels in lung homogenates. NaHS at 300 mu mol/L and 1000 mu mol/L, GYY4137 at 30 mu mol/L and 100 mu mol/L, and AP39 at 30 nmol/L concentrations inhibited the tracheal hyperreactivity to 5-HT, whereas none of these donors affected the enhanced contraction to bradykinin. GYY4137 was also effective to inhibit 5-HT hyperreactivity acutely. In lung tissues, NaHS prevented the elevation of IL-1 beta level at 1000 mu mol/L, and IL-6 and TNF-alpha levels at 100 mu mol/L concentrations. Incubation with GYY4137 (100 mu mol/L) and AP39 (30 nmol/L and 300 nmol/L) inhibited the increase in IL-6 and TNF-alpha levels, but not IL-1 beta at concentrations that they affected tracheal hyperreactivity. These results indicate that H2S donors can decrease inflammation and prevent airway hyperreactivity.