Effects of sucralfate on gastric prostaglandin and leukotriene synthesis: relationship to protective actions

The mechanism of the protective actions of sucralfate against ethanol-induced gastric mucosal damage in the rat has been investigated. In particular, the role of prostaglandins as mediators of such protection was assessed. Oral administration of sucralfate at a dose causing a significant reduction of ethanol-induced gastric damage (500 mg/kg) did not significantly alter gastric 6-ketoprostaglandin F1α synthesis. Pretreatment with indomethacin at a dose that inhibited gastric cyclooxygenase activity by an average of 88% did not affect the protective actions of sucralfate. To further investigate the mechanism of action of sucralfate, an ex vivo gastric chamber model was used in which sucralfate could be applied to only one side of the mucosa. Sucralfate did not affect gastric prostaglandin synthesis, but did cause a significant increase in leukotriene C4 synthesis, a fall in transmucosal potential difference, and a significant decrease in gastric myeloperoxidase activity on the side exposed to sucralfate. These observations suggest that sucralfate has an irritant action on the mucosa. The release of mediators in response to such irritation may play an important role in the protective action of sucralfate. The present study supports the hypothesis that prostaglandins do not mediate the protection afforded by exposure to sucralfate.

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The role of the vagus nerve in the protective action of acid inhibitors on ethanol-induced gastric mucosal damage in rats

Journal of Gastroenterology and Hepatology ◽

10.1111/j.1440-1746.1992.tb00958.x ◽

1992 ◽

Vol 7 (2) ◽

pp. 178-183 ◽

Cited By ~ 16

Author(s):

C. H. CHO ◽

B. W. CHEN ◽

W. M. HUI ◽

S. K. LAM ◽

C. W. OGLE

Keyword(s):

Vagus Nerve ◽

Protective Action ◽

Mucosal Damage ◽

Gastric Mucosal Damage

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Is there a role for leukotrienes as mediators of ethanol-induced gastric mucosal damage?

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1988.254.1.g117 ◽

1988 ◽

Vol 254 (1) ◽

pp. G117-G123 ◽

Cited By ~ 1

Author(s):

J. L. Wallace ◽

P. L. Beck ◽

G. P. Morris

Keyword(s):

Gastric Mucosa ◽

Prostaglandin E1 ◽

Ex Vivo ◽

Mucosal Damage ◽

Gastric Mucosal Damage ◽

Ethanol Administration ◽

Eicosanoid Synthesis ◽

Fourfold Increase ◽

Ethanol Ethanol

The role of leukotriene (LT) C4 as a mediator of ethanol-induced gastric mucosal damage was investigated. Rats were pretreated with a number of compounds, including inhibitors of leukotriene biosynthesis [4-bromo-2,7-dimethoxy-3H-phenothiazin-3-one (L651,392), 3-amino-[m-(trifluoromethyl)-phenyl]-2-pyrazoline hydrochloride (BW755c), and dexamethasone] and agents that have previously been shown to reduce ethanol-induced damage [prostaglandin E2, 2-decarboxy-2-hydroxymethyl-15-deoxy-16RS-hydroxy-16- methyl prostaglandin E1 (Rioprostil), FPL52694] prior to oral administration of absolute ethanol. Ethanol administration resulted in a fourfold increase in LTC4 synthesis. LTC4 synthesis could be reduced significantly by pretreatment with L651,392 or dexamethasone without altering the susceptibility of the gastric mucosa to ethanol-induced damage. LTC4 release from hemorrhagic tissue was not significantly increased above that from samples of nonhemorrhagic tissue from the same stomachs. Furthermore, changes in LTB4 synthesis paralleled the changes in LTC4 synthesis observed after ethanol administration. The effects of ethanol on gastric eicosanoid synthesis were further examined using an ex vivo gastric chamber preparation that allowed for application of ethanol to only one side of the stomach. Such treatment resulted in significant increases in LTC4 synthesis on both sides of the stomach (compared with controls), although the increase on the challenged side was significantly greater than that on the nonchallenged side. These studies, thus, confirm that ethanol can stimulate gastric leukotriene synthesis independent of the production of hemorrhagic damage. Inhibition of LTC4 synthesis does not confer protection to the mucosa, suggesting that LTC4 does not play an important role in the etiology of ethanol-induced gastric damage.

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Role of Lipoxygenases and the Lipoxin A4/Annexin 1 Receptor in Ischemia-Reperfusion-Induced Gastric Mucosal Damage in Rats

Pharmacology ◽

10.1159/000244017 ◽

2009 ◽

Vol 84 (5) ◽

pp. 294-299 ◽

Cited By ~ 15

Author(s):

Brigitta M. Peskar ◽

Karlheinz Ehrlich ◽

Rufina Schuligoi ◽

Bernhard A. Peskar

Keyword(s):

Ischemia Reperfusion ◽

Mucosal Damage ◽

Gastric Mucosal Damage ◽

Lipoxin A4 ◽

Annexin 1

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Abstract 110: Adiponectin Inhibits TNF-a-Induced Vascular Inflammatory Response via Caveolin-Mediated Ceramidase Recruitment and Activation

Circulation Research ◽

10.1161/res.113.suppl_1.a110 ◽

2013 ◽

Vol 113 (suppl_1) ◽

Author(s):

Yajing Wang ◽

Wayne Lau ◽

Erhe Gao ◽

Walter Koch ◽

Xin Ma

Keyword(s):

Inflammatory Response ◽

Protective Action ◽

Receptor Subtype ◽

Protective Actions ◽

Nitrative Stress ◽

S1p Receptor ◽

Anti Inflammatory ◽

Or Gene ◽

First Time

Anti-inflammatory and vascular protective actions of adiponectin (APN) are well-recognized. However, many fundamental questions remain unanswered. The current study attempted to identify the APN receptor subtype responsible for APN’s vascular protective action, and investigate the role of ceramidase activation in APN anti-inflammatory signaling. Wild type (WT) or gene manipulated HUVEC were treated with TNFα in the presence and absence of APN. The effect of APN on TNFα-induced inflammatory and oxidative/nitrative stress was determined. In WT HUVEC, APN significantly reduced TNFα-induced ICAM-1 expression and attenuated TNFα-induced superoxide and peroxynitrite formation (P<0.01). These anti-inflammatory actions were virtually abolished by AdipoR1-, but not AdipoR2-, knockdown (KD). Treatment with APN significantly increased neutral ceramidase (nCDase) activity (3.7-fold, P<0.01). AdipoR1-KD markedly (P0.05), reduced APN-induced nCDase activation. More importantly, siRNA mediated nCDase-KD markedly blocked the effect of APN upon TNFα-induced ICAM-1 expression (P0.05), and modestly inhibited APN anti-inflammatory effect (P87% of APN-induced nCDase activation was lost. Whereas APN treatment failed to inhibit TNFα-induced ICAM-1 expression, treatment with S1P or SEW (S1P receptor agonist) remained effective in Cav1-KD cells in reducing TNFα-induced ICAM-1 expression (P<0.01). AdipoR1 and Cav1 co-localized and co-precipitated in HUVECs. APN treatment did not affect this interaction. Moreover, re-expression of WT Cav1 in Cav1-KD cells restored nCDase activation in response to APN (P<0.01 vs. vehicle), whereas re-expression of a mutated Cav1 blocking AdipoR1/Cav1 interaction failed to restore APN-mediated nCDase activation. Finally, there is weak basal Cav1/nCDase interaction, which significantly increased following APN treatment. These results demonstrate for the first time that APN inhibits TNFα-induced inflammatory response via Cav1-mediated ceramidase recruitment and activation in an AdipoR1- dependent fashion.

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Role of taurocholic acid in production of gastric mucosal damage after ingestion of aspirin.

BMJ ◽

10.1136/bmj.1.5951.183 ◽

1975 ◽

Vol 1 (5951) ◽

pp. 183-185 ◽

Cited By ~ 17

Author(s):

K M Cochran ◽

J F Mackenzie ◽

R I Russell

Keyword(s):

Mucosal Damage ◽

Taurocholic Acid ◽

Gastric Mucosal Damage

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Role of Leukotrienes in Gastric Mucosal Damage and Protection

Prostaglandins and Leukotrienes in Gastrointestinal Diseases ◽

10.1007/978-3-642-73316-1_18 ◽

1988 ◽

pp. 81-87 ◽

Cited By ~ 2

Author(s):

B. M. Peskar

Keyword(s):

Mucosal Damage ◽

Gastric Mucosal Damage

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Role of sensory afferents in the myoelectric response to acute enteric inflammation in the rabbit

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1997.273.2.g447 ◽

1997 ◽

Vol 273 (2) ◽

pp. G447-G455 ◽

Cited By ~ 3

Author(s):

T. Shea-Donohue ◽

J. M. Goldhill ◽

E. Montcalm-Mazzilli ◽

C. Colleton ◽

V. M. Pineiro-Carrero ◽

...

Keyword(s):

Neural Control ◽

Ex Vivo ◽

Neutrophil Infiltration ◽

Mucosal Damage ◽

Myoelectric Activity ◽

Sensory Afferents ◽

Rabbit Small Intestine ◽

Sustained Inhibition

The role of sensory afferents in inflammation-induced alterations in myoelectric activity in vivo was investigated in the rabbit small intestine. Isolated ileal loops were implanted with serosal electrodes and exposed to ricin or vehicle after pretreatment with 125 mg/kg of subcutaneous (125 mg over 3 days) or intraluminal (640 microM) capsaicin. After 5 h of myoelectric recording, the loops were prepared for histology and for ex vivo generation of eicosanoids. Capsaicin exacerbated mucosal damage after exposure to ricin but did not alter neutrophil infiltration. Subcutaneous capsaicin alone elevated slow-wave frequency and spike events and transiently suppressed the myoelectric response to ricin. In contrast, intraluminal capsaicin alone did not alter myoelectric activity but produced a sustained inhibition of the response to ricin. Eicosanoid production was unchanged by capsaicin alone. Intraluminal capsaicin blocked increases in leukotriene C4 and prostaglandin E2 during inflammation, an effect that paralleled its inhibition of myoelectric activity. Thus the contribution of sensory afferents to altered motility during acute ileitis involves the release of mucosal inflammatory mediators that influence neural control of smooth muscle.

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