The present study investigated the role of the endogenous
cystathionine gamma-lyase (CSE) /
hydrogen sulfide pathway in the pathogenesis of
pulmonary fibrosis. Rats treated with intratracheal
bleomycin were exposed either to the H2S donor
NaHS or to saline. The results on day 7 showed that plasma H2S concentration and pulmonary CSE activity (H2S production rate) were significantly lower in rats treated with
bleomycin and saline (
fibrosis-alone) than in controls, whereas on day 28 plasma H2S concentration was higher and pulmonary CSE activity was the same as that of controls. The relative CSE
mRNA level in the lungs of rats treated with
bleomycin was significantly higher than control values on days 7 and 28. After exposure to
NaHS, the total lung
hydroxyproline content and the
malondialdehyde (MDA) content were both significantly lower, with no difference observed between
NaHS high-dose and low-dose treatments. Further, MDA formation stimulated by the
free radical-generating system (FRGS) in vitro was lower in lung tissue incubated with
NaHS than it was in tissue incubated with FRGS alone. These results suggest that
NaHS administration ameliorated the
pulmonary fibrosis induced by
bleomycin in rats and that this protective effect of H2S may be mediated by its antioxidative action.