Gastrointestinal Safety and Anti-Inflammatory Effects of a Hydrogen Sulfide–Releasing Diclofenac Derivative in the Rat

Wallace, John L.; Caliendo, Giuseppe; Santagada, Vincenzo; Cirino, Giuseppe; Fiorucci, Stefano

doi:10.1053/j.gastro.2006.11.042

Cited by 243 publications

(201 citation statements)

References 33 publications

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“…Immunoreactivity for CSE was also observed in the vascular smooth-muscle cells of penile vessels and in the penile artery. These data are in line with the current belief that CSE rather than CBS is more important in H 2 S production at the vascular level (28). In addition, peripheral nerves showed a positive stain to CSE, in contrast to CBS, suggesting that CSE may modulate the L-Cys/H 2 S pathway in peripheral cavernous nerves of man.…”

Section: Discussionsupporting

confidence: 91%

Hydrogen sulfide as a mediator of human corpus cavernosum smooth-muscle relaxation

Bianca

Sorrentino

Maffia

et al. 2009

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

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Section: Discussionsupporting

confidence: 91%

Hydrogen sulfide as a mediator of human corpus cavernosum smooth-muscle relaxation

Bianca

Sorrentino

Maffia

et al. 2009

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

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185

120

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“…Previous studies have documented that the mechanism of aspirin-induced gastric damage involves an inhibition of cytoprotective prostaglandin E 2 production via COX-1/ COX-2 enzymatic activity and the prominent fall in GBF leading to the formation of severe hemorrhagic lesions of gastric mucosa [5,[29][30][31][32][33]. On the other hand, recent studies reported that the endogenous gaseous mediators H 2 S, CO, and NO contribute to the maintenance of gastric mucosal integrity and prevent the formation of gastric mucosal lesions induced by various noxious stimuli, such as exposure to stress or administration of ethanol, bisphosphonates, and NSAIDs, including aspirin [5,17,19,21,22,26,34].…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide, afferent sensory nerves, and antioxidative enzymes in the mechanism of protection mediated by tricarbonyldichlororuthenium(II) dimer and sodium hydrosulfide against aspirin-induced gastric damage

et al. 2017

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Background Aspirin exerts side effects within the gastrointestinal tract. Hydrogen sulfide (H 2 S) and carbon monoxide (CO) have been implicated in gastroprotection but the mechanism of beneficial action of these gaseous mediators against aspirin-induced damage has not been fully studied. We determined the involvement of afferent sensory neurons, calcitonin-gene-related peptide (CGRP), lipid peroxidation, and nitric oxide (NO) biosynthesis in gastroprotection of H 2 S-releasing NaHS and CO-releasing tricarbonyldichlororuthenium(II) dimer (CORM-2) against aspirin-induced injury. Methods Wistar rats with or without capsaicin-induced denervation of sensory neurons were pretreated with vehicle, CORM-2 (5 mg/kg intragastrically), or NaHS (5 mg/kg intragastrically) with or without capsazepine (5 mg/kg intragastrically) or N G -nitro-L-arginine (L-NNA, 20 mg/kg intraperitoneally). The areas of aspirin-induced lesions and gastric blood flow (GBF) were assessed by planimetry and laser flowmetry respectively. Gastric mucosal messenger RNA and/or protein expression of CGRP, heme oxygenase 1, inducible nitric oxide synthase, cyclooxygenase 2, interleukin-1b, glutathione peroxidase 1 (GPx-1), and superoxide dismutase was determined by real-time PCR or Western blot. Malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) content was determined by colorimetric assay. Results Aspirin caused gastric lesions, decreased GBF, and raised MDA content, but pretreatment with NaHS and CORM-2 reduced these effects. Capsaicin-induced denervation or co-treatment with capsazepine reversed the gastroprotective and vasodilatory effects of NaHS but not those of CORM-2. L-NNA reversed NaHS-induced gastroprotection and partly reduced CORM-2-induced gastroprotection. NaHS and CORM-2 decreased MDA and 4-HNE content, restoring GPx-1 protein expression. Conclusions We conclude that H 2 S-but not CO-mediated gastroprotection against aspirin-induced injury involves afferent sensory nerves and partly NO activity. NaHS and CORM-2 prevented aspirin-induced gastric mucosal lipid peroxidation via restoration of microcirculation and antioxidative GPx-1 protein expression.

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“…However, in this study, the anti-inflammatory effect of H 2 S was observed by comparing the effects of H 2 S-releasing NSAID (diclophenac) and H 2 S-non-releasing NSAID (14). H 2 S-releasing drugs were shown to have anti-inflammatory effects (28). In the study of Sidhapuriwala et al (29) investigating the anti-inflammatory effect of H 2 S using NaHS, an H 2 S donor, at 10 mg/kg, a decrease in the inflammation in pancreas and lungs secondary to edematous pancreatitis was observed.…”

Section: Discussionmentioning

confidence: 90%

The anti-inflammatory effect of hydrogen sulphide on acute necrotizing pancreatitis in rats

et al. 2017

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Objective: The aim of this study was to investigate the dose-dependent anti-inflammatory effectof the Hydrogen sulfidedonor sodiumhydrosulphide on acute necrotizing pancreatitis in rats. Material and Methods:A total of 42 male Sprague-Dawley rats were divided into 4 groups: sham+saline (group 1), sham+NaHS (group 2), acute necrotizing pancreatitis+saline (group 3), and acute necrotizing pancreatitis+NaHS (group 4). Acute pancreatitis was induced in rats in groups 3 and 4 with the infusion of glycodeoxycholic acidinto the biliopancreatic canal and infusion of cerulein parenterally. In group 4, 10 mg/kg NaHS was administered intraperitoneally after cerulein infusion.Tests for liver and kidney function, interleukin-6, lactate dehydrogenase in bronchoalveolar lavage, and malonyaldehyde and myeloperoxidase activities in pancreas and lung tissue were performed, and histopathologic examination of pancreas was conducted. Results:In groups 3, a significant increase in amylase, alanine aminotransferase, urea, interleukine-6, lungmalondialdehydeand myeloperoxidase activities, pancreas myeloperoxidase activity, edema, and necrosis in pancreas tissue and a significant decrease in serum calcium levels were detected (p<0.05). In group 4, addition of NaHS resulted in a significant decrease in lactate dehydrogenase level in bronchoalveolar lavage, amount of urea, lung myeloperoxidase activity, and pancreatic edema (p<0.05). Conclusion:Although not in pancreatic necrosis, hydrogen sulphide has an anti-inflammatory effect especially in the inflammatory process in lung and edema in pancreasin acute necrotizing pancreatitis at particular doses. With further studies evaluating the anti-inflammatory effects of hydrogen sulphide, we believe it can be used in the treatment of edematous acute pancreatitis and the related complications in lungs.

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Gastrointestinal Safety and Anti-Inflammatory Effects of a Hydrogen Sulfide–Releasing Diclofenac Derivative in the Rat

Cited by 243 publications

References 33 publications

Hydrogen sulfide as a mediator of human corpus cavernosum smooth-muscle relaxation

Hydrogen sulfide as a mediator of human corpus cavernosum smooth-muscle relaxation

Nitric oxide, afferent sensory nerves, and antioxidative enzymes in the mechanism of protection mediated by tricarbonyldichlororuthenium(II) dimer and sodium hydrosulfide against aspirin-induced gastric damage

The anti-inflammatory effect of hydrogen sulphide on acute necrotizing pancreatitis in rats

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