Anti-Inflammatory and Cytoprotective Actions of Hydrogen Sulfide: Translation to Therapeutics

Wallace, John L.; Blackler, Rory W.; Chan, Melissa; Silva, Gabriela; Elsheikh, Wagdi; Flannigan, Kyle L.; Gamaniek, Iulia; Mańko, Anna; Wang, Lu; Motta, Jean-Paul; Buret, André G.

doi:10.1089/ars.2014.5901

Cited by 137 publications

(103 citation statements)

References 107 publications

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“…Rats and mice were provided one of two diets (Harlan Teklad) for 6 wk. One diet ("B-Def") lacked vitamins B 6 , B 9 , and B 12 (49). The control diet was identical except that it contained the abovementioned vitamins and folate.…”

Section: Methodsmentioning

confidence: 99%

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Impaired hydrogen sulfide synthesis and IL-10 signaling underlie hyperhomocysteinemia-associated exacerbation of colitis

Flannigan

Agbor

Blackler

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Inflammatory bowel diseases (IBDs) are debilitating conditions with no known cure. Recent evidence suggests that elevated intestinal hydrogen sulfide (H 2 S) synthesis promotes healing and reduces inflammation. H 2 S is synthesized from cysteine largely via vitamin B 6 -dependent enzymes. People with IBD are also at increased risk of hyperhomocysteinemia, a condition that is often caused by vitamin B deficiency. Dietary induction of vitamin B deficiency markedly increased serum homocysteine levels and worsened colitis in rodents. The latter was due to the absence of the typical injury-induced elevation of H 2 S synthesis. Interleukin-10 plays a key role in increasing H 2 S synthesis, attenuating the severity of colitis, and reducing serum homocysteine levels. The H 2 S–interleukin 10 axis may be a viable target for therapy of IBD.

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Section: Methodsmentioning

confidence: 99%

“…In recent years, hydrogen sulfide (H 2 S) has become recognized as an important signaling molecule in many organs and tissues (8), and particularly as an anti-inflammatory and cytoprotective mediator (9). H 2 S is produced throughout the gastrointestinal (GI) tract, and its synthesis is markedly increased following mucosal injury (10-13).…”

mentioning

confidence: 99%

Impaired hydrogen sulfide synthesis and IL-10 signaling underlie hyperhomocysteinemia-associated exacerbation of colitis

Flannigan

Agbor

Blackler

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…H 2 S is a novel gasotransmitter that has been shown to exert an important role in regulating vascular tone [13]. There is a rapidly expanding body of evidence for important roles of H 2 S in protecting against tissue injury, reducing inflammation, and promoting repair [14]. In animal studies, H 2 S has been shown to play a role in both promoting and inhibiting inflammation and appears to increase survival in animal model of sepsis and shock [15].…”

Section: Introductionmentioning

confidence: 99%

Carvedilol Could Ameliorate Acetaminophen Overdose Hepatotoxicity. Endogenous H2S Contributes Such Effect: A Comparative Biochemical Evaluation

Allam¹,

Shoman²

2017

Am. J. Biomed. Sci.

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This study was designed to evaluate the effect of acute overdose of acetaminophen exposure, and determine the curative effect of carvedilol and explore the role of endogenous H 2 S. Four groups of rats (n=10): groups I: control group, group II: acetaminophen (APAP) hepatotoxictoxic group, group III: APAP hepatotoxictoxic + carvedilol (CVD) treated group and group IV: APAP hepatotoxictoxic + CVD + hydrogen sulfide (H 2 S) blocker; dl-propargylglycine (PAG) treated group. Animals of groups II, III, IV were given a single overdose of APAP; (2 g/kg) by oral gavages. Groups III and IV received CVD (10 mg/kg/day) by oral gavages, treatment was started 1 hr before APAP administration for 14 days. Animals of group IV received intraperitoneal injection of PAG (45 µmol/kg/day) for 14 days before CVD administration. On the 15th day, blood samples were obtained for estimation of liver enzymes activity levels and animals were sacrificed. Liver was extracted for histological examination and estimation of antioxidant enzymes activity and malondialdhyde (MDA) levels in liver tissue homogenate. Serum liver enzymes activity and MDA levels were significantly higher with significantly lower antioxidant enzymes activity in group II than in groups I and III. Serum liver enzymes activity and MDA levels were significantly higher with reduced antioxidant enzymes activity in group IV than in group III. We concluded that acute acetaminophen exposure destroyed hepatic architecture and altered enzymes activity. Carvedilol has a curative effect through preserved activity of antioxidants. Endogenous H 2 S significantly contributes to carvedilol mediated effect.

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“…However, they do not affect the survival of normal human cells. Several recent studies have shown that H 2 S-releasing NSAIDs, which were initially developed by Wallace et al as anti-inflammatory drugs having no side effects on the gastrointestinal tract, exhibit enhanced chemopreventive effects in cancer cells (7). These compounds inhibit cancer cell proliferation and promote apoptosis, as well as cell cycle arrest.…”

mentioning

confidence: 99%

“…The effects of H 2 S and related compounds on various types of cancers and their ability to suppress cancer development have been described previously (6,7). According to Szabo and colleagues, the production of H 2 S by CBS is increased in colorectal and ovarian cancers and both play an important role in promoting cellular bioenergetics, proliferation, and migration (1).…”

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confidence: 99%

Signaling of Hydrogen Sulfide and Polysulfides

Kimura

2015

Antioxidants & Redox Signaling

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It has been almost two decades since the first demonstration of hydrogen sulfide (H 2 S) as a physiological mediator of cognitive function and vascular tone. H 2 S is physiologically important because it protects various organs from ischemia-reperfusion injury besides regulating inflammation, oxygen sensing, cell growth, and senescence. The production, metabolism, and regulation of H 2 S have been studied extensively. H 2 S modulates target proteins through sulfhydration (or sulfuration) or by the reduction of cysteine disulfide bonds. A large number of novel H 2 S-donating compounds are being developed owing to the therapeutic potential of H 2 S. Recently, polysulfides, rather than H 2 S, have been identified as molecules that sulfhydrate (or sulfurate) their target proteins. Antioxid. Redox Signal. 22, 347-349.

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Anti-Inflammatory and Cytoprotective Actions of Hydrogen Sulfide: Translation to Therapeutics

Cited by 137 publications

References 107 publications

Impaired hydrogen sulfide synthesis and IL-10 signaling underlie hyperhomocysteinemia-associated exacerbation of colitis

Impaired hydrogen sulfide synthesis and IL-10 signaling underlie hyperhomocysteinemia-associated exacerbation of colitis

Carvedilol Could Ameliorate Acetaminophen Overdose Hepatotoxicity. Endogenous H2S Contributes Such Effect: A Comparative Biochemical Evaluation

Signaling of Hydrogen Sulfide and Polysulfides

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