Cytoprotective action of carbenoxolone sodium on ethanol-induced gastric lesions in rats and its inhibition by indomethacin

Wan, B. Y. C.; Gottfried, Sidney P.

doi:10.1111/j.2042-7158.1985.tb04956.x

Cited by 15 publications

(16 citation statements)

References 15 publications

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“…Furthermore, in patients with peptic ulcer disease administration of carbenoxolone was reported to increase the secretion of prostaglandin E2 into the gastric lumen (Rask-Madsen et al, 1983). However, as shown by our results, pretreatment with indomethacin in a dose that causes near-maximal suppression of gastric mucosal prostaglandin formation only partially antagonized the protective activity of carbenoxolone against ethanol-induced rat gastric mucosal damage confirming results published by Wan & Gottfried (1985). The present findings demonstrate that the indomethacin-resistant part of the gastroprotective activity of carbenoxolone is sensitive to inhibition of NO biosynthesis.…”

Section: Discussionsupporting

confidence: 91%

“…This correlation further supports the concept that local pharmacological effects of carbenoxolone, e.g. the increase in mucosal blood flow (Wan & Gottfried, 1985), might be related to increased activity of the endogenous NO system due to the inhibitory action on phosphodiesterases. It remains to be investigated, to what extent the gastroprotection observed with other phosphodiesterase inhibitors such as papaverine (Hagel et al, 1982) is related to increased biological activity of locally formed NO.…”

Section: Discussionsupporting

confidence: 83%

“…Carbenoxolone protects the gastric mucosa against a variety of noxious agents in experimental animals (Derelanko & Long, 1981;Martin et al, 1984) and accelerates peptic ulcer-healing in man (Doll et al, 1962) without inhibiting acid secretion (Baron, 1977). The gastroprotective effect is diminished, but not abolished, by the cyclo-oxygenase inhibitor, indomethacin (Wan & Gottfried, 1985) suggesting that endogenous prostanoids mediate part of the gastroprotection. Other mediators could contribu~te to the carbenoxolone effect.…”

Section: Introductionmentioning

confidence: 99%

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Effect of carbenoxolone on the biological activity of nitric oxide: relation to gastroprotection

Dembińska-Kieć

Pallapies

Simmet

et al. 1991

British J Pharmacology

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1 The interactions between carbenoxolone and nitric oxide (NO) were examined by investigating their effects on human platelet aggregation, on rat aortic strips precontracted by phenylephrine and on protection of rat gastric mucosa against ethanol-induced injury.2 Carbenoxolone (100-300,UM) caused a significant and concentration-dependent potentiation of rat peritoneal neutrophil (RPN)-, 3-morpholino-sydnonimine (SIN-1)-or iloprost-induced inhibition of platelet aggregation. Higher concentrations (5001uM) of carbenoxolone alone markedly inhibited platelet aggregation. Pretreatment with carbenoxolone (100-300pM) antagonized the reversal of the RPN-or SIN-1-induced antiaggregatory effect by oxyhaemoglobin (10Mm).3 Rat aortic strips with intact endothelium precontracted by phenylephrine (0.1-0.31uM) were relaxed by carbenoxolone (100-300,uM) in a concentration-dependent manner. Relaxations were abolished by mechanical removal of the endothelium or by incubation with methylene blue (10pM) or NG-nitro-L-arginine (L-NNA, 100pgM). Sodium nitroprusside (10 nM)-induced relaxations of endothelium-denuded rat aortic strips were potentiated by carbenoxolone (100 UM). 4 The carbenoxolone (200mg kg-1, p.o.)-induced gastroprotection against ethanol was antagonized by L-NNA (5-4Omgkg-1) in a dose-dependent manner. Pretreatment of rats with indomethacin (lOmgkg 1, s.c.) increased the effect of L-NNA. 5 The results suggest that the activity of carbenoxolone in the experimental systems tested is due to phosphodiesterase inhibition, although radical scavenging properties of the drug could contribute to some of the effects observed. In the rat gastric mucosa both increased prostaglandin levels and effects on the NO system could contribute to the protective action of carbenoxolone.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

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Effect of carbenoxolone on the biological activity of nitric oxide: relation to gastroprotection

Dembińska-Kieć

Pallapies

Simmet

et al. 1991

British J Pharmacology

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“…Carbenoxolone increases mucus secretion to protect the gastric mucosa from injury [30]. The participation of PGs and NO in the carbenoxolone‐induced gastroprotective effect has been shown in previous reports [4,7] . Furthermore, we have demonstrated carbenoxolone‐augmented gastric NO and PGs’ levels on ethanol‐induced gastric injury, which could be related to the increase of mucus secretion induced by carbenoxolone pretreatment.…”

Section: Discussionmentioning

confidence: 93%

Carbenoxolone gastroprotective mechanism: participation of nitric oxide/cGMP/KATP pathway in ethanol-induced gastric injury in the rat

Chávez-Piña¹,

Tapia-Álvarez²,

Reyes-Ramínrez³

et al. 2010

Fundamental &Amp; Clinical Pharmacology

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Carbenoxolone, a semi-synthetic triterpenoid, exhibits gastroprotective activity related to the participation of nitric oxide (NO); however, the complete NO/(c) GMP/K(ATP) channels pathway for carbenoxolone is unknown. Therefore the aim of this study was to examine the NO/(c) GMP/K(ATP) channels pathway as the gastroprotective mechanism of carbenoxolone in the ethanol-induced gastric injury model in the rat. Oral administration of carbenoxolone (30 mg/kg, p.o.) exhibited gastroprotective effect against ethanol-induced gastric injury in rats. Pretreatment with N(G) -nitro-l-arginine methyl ester (L-NAME, 70 mg/kg, i.p.); 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ, guanylate cyclase inhibitor, 10 mg/kg, i.p.); or glibenclamide (K(ATP) channels inhibitor, 1 mg/kg, i.p.) reversed the gastroprotective effect of carbenoxolone for ethanol-induced gastric injury. Furthermore, gastric prostaglandins and NO levels increased after carbenoxolone administration in ethanol-induced gastric injury in rats. In conclusion, our results suggest that the increase of NO levels in gastric tissue after pretreatment with carbenoxolone activates the NO/(c)GMP/K(ATP) channels pathway, the principal gastroprotective mechanism of carbenoxolone.

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“…Carbenoxolone (Sigma-Aldrich Co.) was used as a model gastroprotective drug (Wan & Gottfried 1985). The drugs were prepared freshly each time and administered suspended in 0.5% Tween 80 by the intragastric route.…”

Section: Drug and Dosagementioning

confidence: 99%

Gastroprotective effect of Astragaloside IV: role of prostaglandins, sulfhydryls and nitric oxide

Navarrete

Arrieta

Terrones

et al. 2005

Journal of Pharmacy and Pharmacology

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This investigation evaluated the gastroprotective activity of Astragaloside IV, a cycloartane-type triterpene glycoside isolated from Astragalus zahlbruckneri. Gastric mucosal damage was induced in rats by intragastric ethanol (1 mL/rat). Rats treated orally with Astragaloside IV suspended in Tween 80 at 3, 10 and 30 mg kg(-1), showed 15, 37 and 52% gastroprotection, respectively. The gastroprotection observed at 30 mg kg(-1) for this compound was attenuated in rats pretreated with N(G)-nitro-L arginine methyl ester (70 mg kg(-1), i.p), a nitric oxide (NO)-synthase inhibitor, suggesting that the gastroprotective mechanism of this glycoside involves, at least in part, the participation of NO. The gastroprotective effect of Astragaloside IV was not affected by the inhibition of prostaglandin synthesis with indometacin (10 mg kg(-1), s.c.) nor by the block of endogenous sulfhydryls with N-ethylmaleimide (NEM, 10 mg kg(-1), s.c.). Carbenoxolone was used as a gastroprotective model drug and showed a dose-dependent gastroprotective effect (25, 43 and 88% of gastroprotection, at 3, 10 and 30 mg kg(-1), respectively). The partial participation of prostaglandins, sulfhydryls and NO was observed in the gastroprotective mechanism of carbenoxolone.

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Cytoprotective action of carbenoxolone sodium on ethanol-induced gastric lesions in rats and its inhibition by indomethacin

Cited by 15 publications

References 15 publications

Effect of carbenoxolone on the biological activity of nitric oxide: relation to gastroprotection

Effect of carbenoxolone on the biological activity of nitric oxide: relation to gastroprotection

Carbenoxolone gastroprotective mechanism: participation of nitric oxide/cGMP/KATP pathway in ethanol-induced gastric injury in the rat

Gastroprotective effect of Astragaloside IV: role of prostaglandins, sulfhydryls and nitric oxide

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