Analysing the role of COX-2 in acute oesophagitis and in melatonin-exerted protection against experimental reflux oesophagitis in rats

Singh, Pratibha; Singh, Neetu; Palit, Gautam

doi:10.1111/j.2042-7158.2011.01358.x

Cited by 9 publications

(11 citation statements)

References 35 publications

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“…This observation is in line with previous data from our laboratory that NO is involved in the mucosal defense of the esophagus against acid‐ and pepsin‐induced damage caused by the esophageal perfusion of exogenous acid and bile . This is also consistent with the notion that NO cooperates with prostaglandins derived from COX‐1 in the protection of esophageal mucosa against acid reflux as reported before in experimental model of esophagitis in rats . However, the COX‐2‐derived prostaglandins have proinflammatory role in the acute reflux esophagitis because the increase in PGE 2 generation during the onset of acid reflux was completely eliminated with the concurrent treatment with celecoxib, a specific COX‐2 inhibitor .…”

Section: Discussionsupporting

confidence: 91%

“…This is also consistent with the notion that NO cooperates with prostaglandins derived from COX‐1 in the protection of esophageal mucosa against acid reflux as reported before in experimental model of esophagitis in rats . However, the COX‐2‐derived prostaglandins have proinflammatory role in the acute reflux esophagitis because the increase in PGE 2 generation during the onset of acid reflux was completely eliminated with the concurrent treatment with celecoxib, a specific COX‐2 inhibitor . Moreover, exogenous dmPGE 2 exacerbated esophageal injury, increased COX‐2 expression and produced the rise in MPO activity in rats with experimental reflux esophagitis .…”

Section: Discussionsupporting

confidence: 90%

“…However, the COX‐2‐derived prostaglandins have proinflammatory role in the acute reflux esophagitis because the increase in PGE 2 generation during the onset of acid reflux was completely eliminated with the concurrent treatment with celecoxib, a specific COX‐2 inhibitor . Moreover, exogenous dmPGE 2 exacerbated esophageal injury, increased COX‐2 expression and produced the rise in MPO activity in rats with experimental reflux esophagitis . Singh et al.…”

Section: Discussionmentioning

confidence: 99%

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Esophagoprotection mediated by exogenous and endogenous melatonin in an experimental model of reflux esophagitis

Konturek

Brzozowska

Targosz

et al. 2013

Journal of Pineal Research

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Reflux esophagitis is a common clinical entity in western countries with approximately 30% of the population experiencing the symptoms at least once every month. The imbalance between the protective and aggressive factors leads to inflammation and damage of the esophageal mucosa. We compared the effect of exogenous melatonin and melatonin derived endogenously from L-tryptophan with that of pantoprazole or ranitidine in acid reflux esophagitis due to ligation of the rat pylorus and the limiting ridge between the forestomach and the corpus. Four hours after the induction of gastric reflux, an increase in mucosal lesions associated with edema of the submucosa and with the infiltration of numerous neutrophils and the fall in esophageal blood flow (EBF) were observed. Both melatonin and L-tryptophan or pantoprazole significantly reduced the lesion index (LI) and raised the EBF. Pinealectomy that significantly decreased plasma melatonin levels aggravated LI and these effects were reduced by melatonin and L-tryptophan. Luzindole, the MT2 receptor antagonist, abolished the melatonin-induced reduction in LI and the rise in EBF. L-NNA and capsaicin that augmented LI and decreased EBF, also significantly reduced melatonin-induced protection and hyperemia; both were restored with L-arginine and calcitonin gene-related peptide (CGRP) added to melatonin. Upregulation of IL-1β and TNF-α mRNAs and plasma IL-1β and TNF-α levels were significantly attenuated by melatonin and L-tryptophan. We conclude that melatonin protects against acid reflux-induced damage via activation of MT2 receptors mediated by NO and CGRP released from sensory nerves and the suppression of expression and release of TNF-α and IL-1β.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Esophagoprotection mediated by exogenous and endogenous melatonin in an experimental model of reflux esophagitis

Konturek

Brzozowska

Targosz

et al. 2013

Journal of Pineal Research

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“…BB is known to inhibit inflammatory cytokines, such as TNF-α, IL-1β and IL-6, and inflammatory mediators, such as NO (produced by iNOS) and PGE2 (produced by COX-2) (20–25,27–29). In the present study, the gastric volume and the pH of the gastric juice in the RE rats were not significantly altered following treatment with BB, so the BB-treated rats were stimulated by gastric acid to the same extent as the RE control rats.…”

Section: Discussionmentioning

confidence: 99%

“…BB has been demonstrated to suppress proinflammatory responses through AMP-activated protein kinase (AMPK) activation (17–19) and to inhibit inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, and inflammatory mediators, such as nitric oxide [NO; produced by inducible nitric oxide synthase (iNOS)] and prostaglandin E2 [PGE2; produced by cyclooxygenase (COX)-2] (20–25). …”

Section: Introductionmentioning

confidence: 99%

Berberine protects against esophageal mucosal damage in reflux esophagitis by suppressing proinflammatory cytokines

Choo

Roh

2013

Experimental and Therapeutic Medicine

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This study was performed to investigate the effects of berberine (BB) in a rat model of gastroesophageal reflux disease (GERD), induced by pylorus and forestomach ligation. We evaluated cytotoxicity and proinflammatory biomarkers (nitric oxide, interleukin (IL)-1β and prostaglandin E2) in RAW 264.7 cells in vitro and anti-inflammatory effects in vivo. A total of 54 Sprague Dawley rats were divided into six groups: intact control rats; reflux esophagitis (RE) control rats; RE rats treated with 20 mg/kg omeprazole and RE rats treated with BB at doses of 20, 40 and 60 mg/kg, respectively. All rats were fasted. RE was induced by pylorus and forestomach ligation one hour subsequent to the oral treatment. Six hours subsequent to the surgery, the rats were sacrificed, blood was collected from the abdominal vein and the esophagus and stomach were dissected. The gastric volume and the pH of the gastric juice were evaluated, prior to the esophagus being cut longitudinally and an inner mucosal area being imaged, to analyze mucosal damage indices. Proinflammatory biomarkers in the serum, including tumor necrosis factor (TNF)-α, IL-1β, IL-6 and monocyte chemoattractant protein (MCP)-1 were analyzed using an enzyme-linked immunosorbent assay (ELISA) kit, while the mRNA expression of TNF-α, IL-1β, IL-6 and plasminogen activator inhibitor (PAI)-1 was analyzed using a quantitative polymerase chain reaction (qPCR). Esophagic tissue damage in the BB groups was dose-dependently decreased compared with that in the RE control group. This result was consistent with significant reductions in the levels of proinflammatory biomarkers in the serum and in the expression of proinflammatory mRNA, specifically, TNF-α, IL-1β, IL-6 and PAI-1. The results suggest that the anti-inflammatory and protective effects of BB may attenuate the severity of RE and prevent esophageal mucosal damage, in addition to validating the use of BB as a pharmacological treatment for esophageal reflux disease.

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Critical Evaluation of Animal Models of Gastrointestinal Disorders

Johnson

Meerveld

2017

Handbook of Experimental Pharmacology

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Preclinical research remains an important tool for discovery and validation of novel therapeutics for gastrointestinal disorders. While in vitro assays can be used to verify receptor-ligand interactions and test for structural activity of new compounds, only whole-animal studies can demonstrate drug efficacy within the gastrointestinal system. Most major gastrointestinal disorders have been modeled in animals; however the translational relevance of each model is not equal. The purpose of this chapter is to provide a critical evaluation of common animal models that are being used to develop pharmaceuticals for gastrointestinal disorders. For brevity, the models are presented for upper gastrointestinal disorders involving the esophagus, stomach, and small intestine and lower gastrointestinal disorders that focus on the colon. Particular emphasis is used to explain the face and construct validity of each model, and the limitations of each model, including data interpretation, are highlighted. This chapter does not evaluate models that rely on surgical or other non-pharmacological interventions for treatment.

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Analysing the role of COX-2 in acute oesophagitis and in melatonin-exerted protection against experimental reflux oesophagitis in rats

Abstract: Our results suggest that COX-2 plays an important pro-inflammatory role during acute reflux oesophagitis in rats and its inhibition contributes significantly to melatonin-exerted protection against reflux oesophagitis.

Cited by 9 publications

References 35 publications

Esophagoprotection mediated by exogenous and endogenous melatonin in an experimental model of reflux esophagitis

Esophagoprotection mediated by exogenous and endogenous melatonin in an experimental model of reflux esophagitis

Berberine protects against esophageal mucosal damage in reflux esophagitis by suppressing proinflammatory cytokines

Critical Evaluation of Animal Models of Gastrointestinal Disorders

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