Hydrogen sulfide attenuates the pathogenesis of pulmonary fibrosis induced by bleomycin in rats

Fang, Liping; Li, Hong LiH.; Tang, Chaoshu; Geng, Bin; Qi, Yongcheng; Liu, Xinmin LiuX.

doi:10.1139/y09-039

Cited by 52 publications

(51 citation statements)

References 29 publications

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“…21 Moreover, low doses of NaHS (78 and 392 μg/kg/day body weight, twice daily) also reduced pulmonary fibrosis induced by bleomycin. 11 Previous studies demonstrated that H 2 S level in vertebrate blood varied from 10–300 μmol/l by the methylene blue assay. 22, 23 Using a sensitive fluorescent probe, 24 we found the plasma H 2 S level in normal rat was ∼30–40 μmol/l, whereas its counterpart in the UUO rat was 20–30 μmol/l.…”

Section: Discussionmentioning

confidence: 99%

“…10 Emerging evidence also demonstrates that H 2 S exhibits antifibrotic effects in the lung, heart, and liver. 11, 12, 13 Furthermore, H 2 S bears some similarities to the other two gaseous molecules, nitric oxide and carbon monoxide, both of which protect the kidney from renal fibrosis. 14, 15 Taken together, we hypothesize that H 2 S may attenuate renal fibrosis.…”

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confidence: 99%

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Hydrogen sulfide inhibits the renal fibrosis of obstructive nephropathy

Song

Wang

et al. 2014

Kidney International

112

131

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Hydrogen sulfide has recently been found decreased in chronic kidney disease. Here we determined the effect and underlying mechanisms of hydrogen sulfide on a rat model of unilateral ureteral obstruction. Compared with normal rats, obstructive injury decreased the plasma hydrogen sulfide level. Cystathionine-β-synthase, a hydrogen sulfide-producing enzyme, was dramatically reduced in the ureteral obstructed kidney, but another enzyme cystathionine-γ-lyase was increased. A hydrogen sulfide donor (sodium hydrogen sulfide) inhibited renal fibrosis by attenuating the production of collagen, extracellular matrix, and the expression of α-smooth muscle actin. Meanwhile, the infiltration of macrophages and the expression of inflammatory cytokines including interleukin-1β, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in the kidney were also decreased. In cultured kidney fibroblasts, a hydrogen sulfide donor inhibited the cell proliferation by reducing DNA synthesis and downregulating the expressions of proliferation-related proteins including proliferating cell nuclear antigen and c-Myc. Further, the hydrogen sulfide donor blocked the differentiation of quiescent renal fibroblasts to myofibroblasts by inhibiting the transforming growth factor-β1-Smad and mitogen-activated protein kinase signaling pathways. Thus, low doses of hydrogen sulfide or its releasing compounds may have therapeutic potentials in treating chronic kidney disease.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Hydrogen sulfide inhibits the renal fibrosis of obstructive nephropathy

Song

Wang

et al. 2014

Kidney International

112

131

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“…The kidney also plays a major role in Hcy metabolism [31] and plasma total Hcy increases with the declines of renal function [29]. Hcy, however, in the mammalian tissue can be metabolized further using three endogenous enzymes (CBS, CSE and 3MST) to produce H 2 S. Although H 2 S has been known for decades as a toxic gas with intoxication effects on the central nervous system and respiratory system, recently it has been documented as an important physiological gaseous molecule with antioxidant [13,18], antihypertensive [32], anti-inflammatory [10,16] and antifibrotic [33,34] properties.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide Regulates Homocysteine-Mediated Glomerulosclerosis

et al. 2010

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Background/Aims: In this study we tested the hypothesis that H₂S regulates collagen deposition, matrix metalloproteinases (MMP) and inflammatory molecules during hyperhomocysteinemia (HHcy) resulting in attenuation of glomerulosclerosis and improved renal function. Materials and Methods: A genetic model of HHcy, cystathionine β-synthase heterozygous (CBS+/–) and wild-type (WT) 2-kidney (2K) mice were used in this study and supplemented with or without NaHS (30 µmol/l, H₂S donor) in drinking water for 8 weeks. To expedite the renal damage associated with HHcy, uninephrectomized (1K) mice of similar groups were also used. Results: Results demonstrated that NAD(P)H oxidase (p47^phoxsubunit) and blood pressure were upregulated in WT 1K, CBS+/– 2K and CBS+/– 1K mice with downregulation of H₂S production and reduced glomerular filtration rate. These changes were normalized with H₂S supplementation. Both pro- and active MMP-2 and -9 and collagen protein expressions and glomerular depositions were also upregulated in WT 1K, CBS+/– 2K and CBS+/– 1K mice. Increased expressions of inflammatory molecules, intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1, as well as increased macrophage infiltration, were detected in WT 1K, CBS+/– 2K and CBS+/– 1K mice. These changes were ameliorated with H₂S supplementation. Conclusion: Together, these results suggest that increased oxidative stress and decreased H₂S in HHcy causes matrix remodeling and inflammation resulting in glomerulosclerosis and reduced renal function.

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“…H 2 S is a newly identified endogenous gaseous signaling molecule. Evidences have suggested that H 2 S is protective against inflammation in various fibrosis-related diseases [5,6,7,20,21]. We previously demonstrated, at a relatively low dose (56 µg/kg/day), NaHS protected against UUO by attenuating the infiltration of macrophages and the expression of tumor necrosis factor-alpha in renal cortex [7].…”

Section: Discussionmentioning

confidence: 99%

“…In the past decade, modulation of endogenous H 2 S through either its enzymatic inhibitors or H 2 S-donor compounds represented therapeutic potential for a variety of human diseases related with chronic inflammation and organ fibrosis. Recent evidences demonstrate that exogenous H 2 S attenuates aortic-coarctation-induced cardiac hypertrophy and fibrosis [5], bleomycin-induced pulmonary fibrosis [6], unilateral ureteral obstruction (UUO)-induced kidney fibrosis [7] and carbon tetrachloride-induced cirrhosis [8]. The underlying anti-fibrotic mechanisms of H 2 S may be explained by inhibiting the activation and migration of inflammatory cells as well as myofibroblasts, subsequently attenuating the production of pro-inflammatory cytokines and extracellular matrix (ECM) accumulation [8,9,10].…”

Section: Introductionmentioning

confidence: 99%

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

Lu¹,

Gao²,

et al. 2015

Nephron

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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.

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Hydrogen sulfide attenuates the pathogenesis of pulmonary fibrosis induced by bleomycin in rats

Cited by 52 publications

References 29 publications

Hydrogen sulfide inhibits the renal fibrosis of obstructive nephropathy

Hydrogen sulfide inhibits the renal fibrosis of obstructive nephropathy

Hydrogen Sulfide Regulates Homocysteine-Mediated Glomerulosclerosis

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

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