Inhibitory effects of hydrogen sulphide on pulmonary fibrosis in smoking rats via attenuation of oxidative stress and inflammation

Abstract

Accumulating evidence has demonstrated that hydrogen sulphide (H2S) is involved in the pathogenesis of various respiratory diseases. In the present study, we established a rat model of passive smoking and investigated whether or not H2S has protective effects against pulmonary fibrosis induced by chronic cigarette smoke exposure. Rat lung tissues were stained with haematoxylin-eosin and Masson's trichrome. The expression of type I collagen was detected by immunohistochemistry. Oxidative stress was evaluated by detecting serum levels of malondialdehyde, superoxide dismutase and glutathione peroxidase and measuring reactive oxygen species generation in lung tissue. Inflammation was assessed by measuring serum levels of inflammatory cytokines, including high-sensitivity C-reactive protein, tumour necrosis factor-α, interleukin (IL)-1β and IL-6. The protein expression of Nrf2, NF-κB and phosphorylated mitogen-activated protein kinases (MAPKs) in the pulmonary tissue was determined by Western blotting. Our findings indicated that administration of NaHS (a donor of H2S) could protect against pulmonary fibrosis in the smoking rats. H2S was found to induce the nuclear accumulation of Nrf2 in lung tissue and consequently up-regulate the expression of antioxidant genes HO-1 and Trx-1 in the smoking rats. Moreover, H2S could also reduce cigarette smoking-induced inflammation by inhibiting the phosphorylation of ERK 1/2, JNK and p38 MAPKs and negatively regulating NF-κB activation. In conclusion, our study suggests that H2S has protective effects against pulmonary fibrosis in the smoking rats by attenuating oxidative stress and inflammation.