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

J Cell Mol Med. 2014 Jun;18(6):1098-103. doi: 10.1111/jcmm.12254. Epub 2014 Mar 13.


Accumulating evidence has demonstrated that hydrogen sulphide (H2 S) 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 H2 S 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 H2 S) could protect against pulmonary fibrosis in the smoking rats. H2 S 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, H2 S 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 H2 S has protective effects against pulmonary fibrosis in the smoking rats by attenuating oxidative stress and inflammation.

Keywords: hydrogen sulphide; inflammation; oxidative stress; pulmonary fibrosis; smoking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air Pollutants / pharmacology
  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Electrophoretic Mobility Shift Assay
  • Enzyme-Linked Immunosorbent Assay
  • Hydrogen Sulfide / pharmacology*
  • Immunoenzyme Techniques
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Male
  • Mice
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects*
  • Phosphorylation / drug effects
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / metabolism
  • Pulmonary Fibrosis / pathology
  • Pulmonary Fibrosis / prevention & control*
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Smoking / adverse effects*


  • Air Pollutants
  • NF-kappa B
  • Reactive Oxygen Species
  • Hydrogen Sulfide