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.

Hydrogen sulfide attenuates paraquat‐induced epithelial‐mesenchymal transition of human alveolar epithelial cells through regulating transforming growth factor‐β1/Smad2/3 signaling pathway

“…The irreversible and progressive pulmonary fibrosis leading to respiratory function failure is still the main cause of PQ‐induced death (Dinis‐Oliveira et al, ). Recently, increasing evidence indicates that plasma H 2 S is low level in several animal models of fibrotic diseases and a supplement of exogenous H 2 S is able to ameliorate fibrosis in the kidney (Han et al, ; L. Li et al, ; Li, Li, Zeng, Liu, & Yang, ), heart (Li et al, ; Liang et al, ; Liu et al, ), liver (Mani, Cao, Wu, & Wang, ), peritoneum (Lu et al, ), skin and lung (Fang et al, ; Wang et al, ). As a significant process towards fibrogenesis, EMT characterizes the morphological changes associated with the downregulation of epithelial cell markers, such as E‐cadherin, and upregulation of mesenchymal markers, such as vimentin (Cannito et al, ).…”

The protective effect of hydrogen sulfide on systemic sclerosis associated skin and lung fibrosis in mice model

“…In the 1990s, it was discovered that endogenous H 2 S participated in anti-inflammation, anti-oxidation, and the regulation of cell proliferation and apoptosis (Gao et al 2012 ; Moody and Calvert 2011 ; Vandiver and Snyder 2012 ). Past studies have confirmed that exogenous H 2 S attenuates aortic-coarctation-induced cardiac hypertrophy and fibrosis (Huang et al 2012 ), inhibit renal interstitial fibrosis caused by obstructive nephropathy (Song et al 2014 ), relieve peritoneal mesothelial cell injury caused by high-glucose peritoneal dialysis fluids (Lu et al 2015 ) and carbon tetrachloride-induced cirrhosis (Tan et al 2011 ). The potential mechanisms of H 2 S anti-fibrotic may be account for inhibiting the activation and migration of inflammatory cells likewise myofibroblasts, subsequently decrease the production of pro-inflammatory cytokines and extracellular matrix accumulation (Li et al 2008 ; Tan et al 2011 ).…”

Effects of hydrogen sulphide donor, sodium hydrosulphide treatment on the erectile dysfunction in L‐NAME‐induced hypertensive rats

“…In a study by Hou et al (), exogenous H 2 S can partially prevent ageing‐related kidney dysfunction by decreasing collagen deposition in mice. A recent study demonstrated that H 2 S alleviated peritoneal fibrosis via attenuating inflammation (Lu et al, ). The finding suggests that the antifibrotic effects of NaHS through NF‐κB and H 2 S pathways may contribute to the amelioration of diminished erectile function related to hypertension.…”