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

Abstract

We aimed to investigate and compare the effects of rapid (NaHS) and slow (GYY4137 and AP39) hydrogen sulfide (H₂ S) 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 µg/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-1β, IL-6 and TNF-α levels in lung homogenates. NaHS at 300 µmol/L and 1000 µmol/L, GYY4137 at 30 µmol/L and 100 µmol/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-1β level at 1000 μmol/L, and IL-6 and TNF-α levels at 100 μmol/L concentrations. Incubation with GYY4137 (100 µmol/L) and AP39 (30 nmol/L and 300 nmol/L) inhibited the increase in IL-6 and TNF-α levels, but not IL-1β at concentrations that they affected tracheal hyperreactivity. These results indicate that H₂ S donors can decrease inflammation and prevent airway hyperreactivity.

Keywords: AP39; GYY4137; airway hyperreactivity; airway inflammation; hydrogen sulfide.