Hydrogen Sulfide Alleviates Peritoneal Fibrosis via Attenuating Inflammation and TGF-β1 Synthesis

Abstract

Background/Aims: Peritoneal fibrosis is one of the long-term complications in peritoneal dialysis (PD) patients. Recent evidences have suggested that hydrogen sulfide (H₂S) is beneficial in treating various fibrotic diseases, including pulmonary fibrosis, cirrhosis, kidney fibrosis and cardiac hypertrophy. However, no information is known about the effect of H₂S on peritoneal fibrosis. In the present study, we investigated the effect of H₂S on peritoneal fibrosis and explored its potential mechanisms. Methods: We developed a model of peritoneal fibrosis by intraperitoneally injecting 4.25%-glucose PD fluids and lipopolysaccharide to Sprague-Dawley rats. The rats received daily intraperitoneal injections of NaHS (56 μg/kg), an H₂S donor. After 28 days, the peritoneal equilibration test (PET) was used to assess peritoneal function. At the end of dialysis, the rats were killed and parietal peritoneum was harvested for microscopic examination and immunohistochemistry. Results: On the 28th day, the parietal peritoneum of the PD rats markedly thickened as a result of increased depositions of type III collagen and fibronectin. Moreover, the number of ED-1-positive cells and the expressions of monocyte chemoattractant protein-1, transforming growth factor-β1 (TGF-β1), α-smooth muscle actin and CD31 were significantly increased in the fibrotic peritoneum. Administration of NaHS markedly decreased the biomarkers of inflammation, fibrosis and angiogenesis in the peritoneum. NaHS also improved peritoneal function assessed by PET. Conclusion: Exogenous H₂S ameliorates the pathologic process of peritonitis via attenuating inflammatory events and TGF-β1 synthesis. These results suggest that H₂S may be a potential therapy against peritoneal fibrosis during chronic PD. In the future, compounds releasing H₂S at controlled rate will be assessed as potential candidates to treat peritoneal fibrosis.