Diazoxide, a K<sub>ATP</sub>opener, accelerates restitution of ethanol or indomethacin‐induced gastric ulceration in rats independent of polyamines

Rahgozar, M; Pazoki‐Toroudi, Hamidreza; Bakhtiarian, Azam; Djahanguiri, B

doi:10.1046/j.1440-1746.2001.02433.x

Cited by 38 publications

(28 citation statements)

References 22 publications

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“…It has also been shown that NSAIDs contribute to ulcer formation and delay ulcer healing by inhibiting intestinal epithelial cell migration and mucosal restitution [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…Restitution occurs within minutes to hours following injury in vivo or in vitro, because this process requires cell migration but not cell proliferation or differentiation [17][18][19][20]. While it is established that NSAIDs promote ulceration by interfering with restitution [14][15][16], the signaling pathways mediating this effect have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Depolarization and decreased surface expression of K+ channels contribute to NSAID-inhibition of intestinal restitution

Freeman

Narváez

McCoy

et al. 2007

Biochemical Pharmacology

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Non-steroidal anti-inflammatory drugs (NSAIDs) contribute to gastrointestinal ulcer formation by inhibiting epithelial cell migration and mucosal restitution; however, the drug-affected signaling pathways are poorly defined. We investigated whether NSAID inhibition of intestinal epithelial migration is associated with depletion of intracellular polyamines, depolarization of membrane potential (E m ) and altered surface expression of K + channels. Epithelial cell migration in response to the wounding of confluent IEC-6 and IEC-Cdx2 monolayers was reduced by indomethacin (100 μM), phenylbutazone (100 μM) and NS-398 (100 μM) but not by SC-560 (1 μM). NSAIDinhibition of intestinal cell migration was not associated with depletion of intracellular polyamines. Treatment of IEC-6 and IEC-Cdx2 cells with indomethacin, phenylbutazone and NS-398 induced significant depolarization of E m , whereas treatment with SC-560 had no effect on E m . The E m of IEC-Cdx2 cells was: −38.5±1.8 mV under control conditions; −35.9±1.6 mV after treatment with SC-560; −18.8±1.2 mV after treatment with indomethacin; and −23.7±1.4 mV after treatment with NS-398. Whereas SC-560 had no significant effects on the total cellular expression of K v 1.4 channel protein, indomethacin and NS-398 decreased not only the total cellular expression of K v 1.4, but also the cell surface expression of both K v 1.4 and K v 1.6 channel subunits in IEC-Cdx2. Both K v 1.4 and K v 1.6 channel proteins were immunoprecipitated by K v 1.4 antibody from IEC-Cdx2 lysates, indicating that these subunits co-assemble to form heteromeric K v channels. These results suggest that NSAID inhibition of epithelial cell migration is independent of polyamine-depletion, and is associated with depolarization of E m and decreased surface expression of heteromeric K v 1 channels.

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“…It has also been shown that NSAIDs contribute to ulcer formation and delay ulcer healing by inhibiting intestinal epithelial cell migration and mucosal restitution [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Depolarization and decreased surface expression of K+ channels contribute to NSAID-inhibition of intestinal restitution

Freeman

Narváez

McCoy

et al. 2007

Biochemical Pharmacology

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“…Contact of gastric mucosal epithelium with ethanol results in the release of endothelins, decrease of nitric oxide synthase, and attenuation of nitric oxide synthesis that will lead to reduced blood supply to the gastric mucosal cells. [2,3] Restriction of the microvascular circulation of the gastric epithelium ensures nutrient and oxygen deprivation to the affected mucosae, accumulation of arachidonic metabolites, generation of reactive oxygen species, polymorphonuclear (PMN) infiltration and adhesions, depletion of gastric mucus, plasma leakages of sodium and potassium ions, and edema. [4][5][6] These unfavorable gastric activities may overwhelm the antioxidant capacity of the system, which lead to oxidative stress that could result in gastric cell membrane damage, apoptosis, exfoliation, epithelial erosion, and formation of gastric ulcer.…”

mentioning

confidence: 99%

“…[5] Tissue necrosis factor-α (TNF-α) along with adenosine, histamine, and leukotrienes are considered as the mediators of early vascular injury in ethanol-induced gastric damage. [2,3,7] TNF-α causes polymorphonuclear (PMN) migration through upregulation of the expression of adhesion molecules in neutrophils and endothelial cells. The migration of PMN is an essential ingredient in the several pathways leading to gastric mucosal disruption.…”

mentioning

confidence: 99%

Modulation of Vascular Endothelial Growth Factor (VEGF) and Tissue Necrosis Factor Alpha (TNFα) by the Ethanol Stem Bark Extract of Boswellia dalzielli H Attenuates Ethanol Induced Gastric Ulcer in Albino Rats.

Yusuf

Salami

Babakura

et al. 2018

EJMO

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Objectives:The modulation of vascular endothelial growth factor, antioxidants, and tissue necrosis factor alpha (TNF-α) using ethanol stem bark extract of Boswellia dalzielii H. was evaluated in an ethanol-induced gastric ulcer albino rat model. Methods: Thirty albino rats of either sex (200-250 g) were starved for 48 h but were allowed drinking water with 8% sucrose to avoid dehydration. The rats were placed on wire gauze above the base of the cage to prevent coprophagy. At the end of the fasting period, the rats were equally divided and assigned to six treatment groups. Group A served as control and 5 ml/kg distilled water was orally administered to the rats without further treatment. Rats in group B were given 5 ml/kg distilled water and served as negative control. Rats in groups C, D, and E were pretreated with 100, 200, and 400 mg/kg of the ethanol stem bark extract of B. dalzielii H, respectively. Group F received 50 mg/kg ranitidine. After 1 h, all the rats in groups B-F were each given absolute ethanol 1 ml/200 g body weight of rat. All treatments were by intragastric lavage. One hour after the treatment with ethanol, all the rats in the experiment (groups A-F) were euthanized with an overdose of anesthetic ether and their stomachs were excised. The stomachs were cut along the greater curvature and washed in warm normal saline. Each stomach was stretched out and pinned on board. Results:The results of the study revealed that pretreatment with ethanol stem bark extract of B. dalzielii H. decreased gross and histological gastric mucosal damage caused by intragastric administration of absolute ethanol in a dosedependent manner when compared with controls. The gastric ulcer index and gastric tissue level of malondialdehyde (MDA) and TNF-α were significantly reduced (p<0.001), whereas the gastric tissue level of superoxide dismutase, catalase, total antioxidant capacity, and vascular endothelial growth factor (VEGF) was significantly increased (p<0.001) when compared with the controls. Conclusion: The plant extract attenuated gastric mucosal damage induced by ethanol via upregulation in the expression of gastric tissue VEGF, reinforcement of the antioxidant system, and reduction in the gastric tissue level of MDA and the pro-inflammatory cytokine TNF-α.

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“…In fact, K ATP channel function has been quite extensively studied in several gastrointestinal models. The K ATP channel opener diazoxide has been shown to attenuate the damage and/or accelerate the restitution of indomethacin-and ethanol-induced intestinal and gastric injury in rats and mice (2,87,98,113,114,122,142), whereas K ATP channel inhibition worsened damage parameters. Moreover, the gastroprotective effect of different compounds, such as the steroid saponin hecogenin (122), the antidepressant drug citalopram (124), or prostaglandins (108), seems dependent on K ATP channel function.…”

Section: Mechanisms Responsible For Control Of Cell Migration/prolifementioning

confidence: 99%

Evidence of K⁺ channel function in epithelial cell migration, proliferation, and repair

Girault

Brochiero

2014

American Journal of Physiology-Cell Physiology

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Diazoxide, a K_ATPopener, accelerates restitution of ethanol or indomethacin‐induced gastric ulceration in rats independent of polyamines

Abstract: The K(ATP) channels may play an important role in the gastric mucosal restitution independent of polyamines. Acid inhibition cannot reverse EAGU.

Cited by 38 publications

References 22 publications

Depolarization and decreased surface expression of K+ channels contribute to NSAID-inhibition of intestinal restitution

Depolarization and decreased surface expression of K+ channels contribute to NSAID-inhibition of intestinal restitution

Modulation of Vascular Endothelial Growth Factor (VEGF) and Tissue Necrosis Factor Alpha (TNFα) by the Ethanol Stem Bark Extract of Boswellia dalzielli H Attenuates Ethanol Induced Gastric Ulcer in Albino Rats.

Evidence of K⁺ channel function in epithelial cell migration, proliferation, and repair

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Diazoxide, a KATPopener, accelerates restitution of ethanol or indomethacin‐induced gastric ulceration in rats independent of polyamines

Abstract: The K(ATP) channels may play an important role in the gastric mucosal restitution independent of polyamines. Acid inhibition cannot reverse EAGU.

Cited by 38 publications

References 22 publications

Depolarization and decreased surface expression of K+ channels contribute to NSAID-inhibition of intestinal restitution

Depolarization and decreased surface expression of K+ channels contribute to NSAID-inhibition of intestinal restitution

Modulation of Vascular Endothelial Growth Factor (VEGF) and Tissue Necrosis Factor Alpha (TNFα) by the Ethanol Stem Bark Extract of Boswellia dalzielli H Attenuates Ethanol Induced Gastric Ulcer in Albino Rats.

Evidence of K+ channel function in epithelial cell migration, proliferation, and repair

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Diazoxide, a K_ATPopener, accelerates restitution of ethanol or indomethacin‐induced gastric ulceration in rats independent of polyamines

Evidence of K⁺ channel function in epithelial cell migration, proliferation, and repair