Intranasal treatment with hydrogen sulfide releasing donors can prevent bleomycin-induced pulmonary fibrosis in mice

Pulmonary fibrosis is a chronic, progressive lung disease with a high mortality and there is a significant need for new therapeutic approaches. Hydrogen sulfide (H₂S) is a gas mediator and shown to has anti-fibrotic effects. In this study, we have investigated the potential of H₂S releasing donors (rapid-releasing NaHS and slow-releasing GYY4137) in the treatment of bleomycin-induced pulmonary fibrosis model in mice. Bleomycin (2U/kg) was administered intratracheally to male C57Bl/6 mice. NaHS or GYY4137 (1-3mg/kg) treatments were started on 7^th day via intranasal route, applied each day for two weeks. Samples were collected 24 hours after the last application. NaHS (3mg/kg) treatment slightly prevented the lung compliance and the decrease of total protein and TNF-α levels in BALF, but there was no improvement neither in Aschroft scores nor the fibrotic protein expression levels of the lung tissues. GYY4137 (1mg/kg) prevented the decrease in lung compliance (0.027±0.002ml/cmH₂O vs. 0.019±0.002ml/cmH₂O in bleomycin group; n=5-7), showed a tendency to decrease lymphocyte cell counts (41.60±2.84% vs. 56.19±11.71% in bleomycin group; n=5-7) and total protein concentration in BALF (826.78±129.57mg/ml vs. 1593.93±319.35 in bleomycin group; n=5-7), and decreased Ashcroft scores (2.33±0.88 vs. 4.33±0.96 in bleomycin group; n=5-7). Treatment with a higher dose (3mg/kg) of GYY4137 was not effective. These findings suggest that, slow H₂S releasing donors which mimic the endogenous production may be a new therapeutic approach for pulmonary fibrosis, however, the dose should be justified. Supported by Health Institutes of Türkiye (TUSEB) (4569).