Cytoprotective and Ulcer Healing Properties of Prostaglandin E&lt;sub&gt;2&lt;/sub&gt;, Colloidal Bismuth and Sucralfate in Rats

Konturek, Stanisław J.; Stachura, Jerzy; Radecki, T; Drozdowicz, Danuta; Brzozowski, Tomasz

doi:10.1159/000199579

Cited by 56 publications

(42 citation statements)

References 12 publications

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“…dose-dependently inhibited food intake stimulated by ghrelin in rats with GF. At the dose used in the present study, indomethacin has been shown previously to inhibit gastric PGE 2 generation by ϳ90% without itself causing any mucosal damage (Konturek et al, 1987). The doses of SC560 and rofecoxib were selected on the basis of previous studies showing that these agents almost completely suppress PGE 2 generation in exudate of air pouch inflammation and inhibit gastric PGE 2 production in mucosa with preexisting gastric ulcer (Lesch et al, 1998;Brzozowski et al, 2001).…”

Section: Methodsmentioning

confidence: 99%

Prostaglandin/Cyclooxygenase Pathway in Ghrelin-Induced Gastroprotection against Ischemia-Reperfusion Injury

Brzozowski

Konturek²,

Śliwowski³

et al. 2006

J Pharmacol Exp Ther

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Ghrelin is involved in the control of food intake, but its role in gastroprotection against the formation of gastric mucosal injury has been little elucidated. We studied the effects of peripheral (i.p.) and central (i.c.v.) administration of ghrelin on gastric secretion and gastric mucosal lesions induced by 3 h of ischemia/reperfusion (I/R) with or without inhibition of ghrelin growth hormone secretagogue type 1a receptor (GHS-R1a) by using ghrelin antagonist, D-Lys 3 -GHRP-6; blockade of cycloox-and COX-2 (rofecoxib); and bilateral vagotomy or capsaicin denervation. I/R produced typical gastric erosions, a significant fall in the gastric blood flow (GBF), an increase in gastric myeloperoxidase (MPO) activity and malonyldialdehyde (MDA) content, and the up-regulation of mucosal ghrelin mRNA. Ghrelin dose-dependently increased gastric acid secretion and significantly reduced I/R-induced gastric erosions, while producing a significant rise in the GBF and mucosal PGE 2 generation and a significant fall in MPO activity and MDA content. The protective and hyperemic activities of ghrelin were significantly attenuated in rats pretreated with D-Lys 3 -GHRP-6 and capsaicin denervation and completely abolished by vagotomy. Indomethacin, SC560, and rofecoxib, selective COX-1 and COX-2 inhibitors, attenuated ghrelin-induced protection that was restored by supplying the methyl analog of prostaglandin (PG) E 2 . The expression of mRNA for COX-1 was unaffected by ghrelin, but COX-2 mRNA and COX-2 protein were detectable in I/R injured mucosa and further up-regulated by exogenous ghrelin. We conclude that ghrelin exhibits gastroprotective and hyperemic activities against I/R-induced erosions, the effects that are mediated by hormone activation of GHS-R1a receptors, COX-PG system, and vagal-sensory nerves.

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Section: Methodsmentioning

confidence: 99%

Prostaglandin/Cyclooxygenase Pathway in Ghrelin-Induced Gastroprotection against Ischemia-Reperfusion Injury

Brzozowski

Konturek²,

Śliwowski³

et al. 2006

J Pharmacol Exp Ther

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“…As expected, PG analogs significantly enhanced the spontaneous healing of acetic acid ulcers and prevented a delay in ulcer healing by repeated indomethacin treatment. [93][94][95][96][97] Penney et al 98) demonstrated that misoprostol reversed the delayed healing effect of aspirin via an effect on epithelial regeneration. Arakawa et al 99) examined the effects of rebamipide, a novel PG-inducer, on healing and relapse of acetic acid ulcers in rats.…”

Section: Mucosal Defensive Drugsmentioning

confidence: 99%

An Overview of Acetic Acid Ulcer Models<br>—The History and State of the Art of Peptic Ulcer Research—

Okabe

Amagase

2005

Biological & Pharmaceutical Bulletin

208

166

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Four types of experimental chronic ulcer models, named acetic acid ulcer models, have been developed to examine the healing process of peptic ulcers, screen anti-ulcer drugs, and better evaluate the adverse effects of various anti-inflammatory drugs on the gastrointestinal mucosa. The model easily and reliably produces round, deep ulcers in the stomach and duodenum, allowing acetic acid ulcer production in mice, rats, Mongolian gerbils, guinea pigs, cats, dogs, miniature pigs, and monkeys. These ulcer models highly resemble human ulcers in terms of both pathological features and healing process. The models have been established over the past 35 years and are now used throughout the world by basic and clinical scientists. One of the characteristic features of acetic acid ulcers in rats is the spontaneous relapse of healed ulcers Ͼ100 d after ulceration, an endoscopically confirmed phenomenon. Indomethacin significantly delays the healing of acetic acid ulcers, probably by reducing endogenous prostaglandins and inhibiting angiogenesis in ulcerated tissue. Helicobacter pylori significantly delays healing of acetic acid ulcers and causes relapse of healed ulcers at a high incidence in Mongolian gerbils. Anti-secretory drugs (e.g. omeprazole), prostaglandin analogs, mucosal defense agents (e.g. sucralfate), and various growth factors all significantly enhance healing of acetic acid ulcers. Gene therapy with epidermal growth factor and vascular endothelial growth factor applied to the base of acetic acid ulcers in rats is effective in enhancing ulcer healing. Since an inhibitor of nitric oxide syntase prevents ulcer healing, nitric oxide might be involved in the mechanism underlying ulcer healing. We conclude that acetic acid ulcer models are quite useful for various studies related to peptic ulcers.

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“…Since Konturek et al (37) indicated that ulcer healing rate is dependent on its initial size, it is possible that shrinkage of ulcer size causes ulcer healing. In the present study, we found that the length of the ruptured muscularis mucosa in aged animals was significantly less than that in young animals, indicating that aging promotes tissue contraction.…”

Section: Gastric Motilitymentioning

confidence: 99%

Changes in Gastric Function and Healing of Chronic Gastric Ulcers in Aged Rats

Tsukimi

Okabe

1995

Japanese Journal of Pharmacology

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ABSTRACT-The present study was designed to determine the relationship between changes in gastric function caused by aging and the healing of gastric ulcers. Male Fischer-344 rats (young, 2 months; aged, 24-26 months) were used. Gastric ulcers were induced by luminal application of an acetic acid solution (60%, 0.2 ml, 45 sec). The basal and histamine-stimulated gastric acid secretions in aged animals were significantly lower than those in young animals. However, the serum gastrin levels were almost the same in the two groups. Gastric mucosal blood flow and mucosal cell proliferation were also decreased in aged animals. Gastric contractile activity induced by electrical vagal stimulation was almost the same in the two groups, while the gastric relaxative response was significantly reduced in aged animals. The development and healing rate of gastric ulcers in aged animals were almost the same as those in young animals. Histologically, regeneration of the ulcerated mucosa was significantly reduced and tissue contraction occurred in aged animals, as compared to in young animals. We concluded that aging had little or no influence on the development and healing rate of gastric ulcers in rats, but the quality of ulcer healing was quite different between young and aged animals, probably resulting from various gastric dysfunctions related to ulcer healing. It is well-known that aging causes many functional changes in the body. Several investigators have already reported changes in functions such as gastric secretion (1, 2) and the serum gastrin level (3 -6), gastric mucosal blood flow (7), bicarbonate secretion (8), and mucosal cell proliferation (4) in the stomach of aged animals. O'Brien et al. (9) reported that aging had no influence on the spontaneous healing of acetic acid ulcers in 2-and 12-monthold rats. In general, gastric acid secretion, gastric mucosal blood flow and mucosal cell proliferation are considered to be profoundly involved in ulcer healing (10). Recently, we reported the importance of tissue contraction in the healing of gastric ulcers in rats (11,12). The aim of this study was to compare the functional changes in the stomachs of young (2-month-old) and aged (24-to 26-month-old) rats and to compare the development and healing of chronic gastric ulcers in the two groups. AnimalsYoung (2-month-old, 180 -200 g) and aged (24-to 26-month-old, 420-450 g) male Fischer-344 rats (Charles River, Kanagawa) were used. The animals had free access to laboratory rat chow (CE-2; Nihon Clea, Osaka) and tap water. The animals were deprived of food for 24 hr before the experiments unless stated otherwise. Drinking water was freely available to the animals up to 2 hr before the experiments. During fasting, all animals were kept in mesh-bottom cages to prevent coprophagy. All experiments were performed with paired young and aged animals, and 4 to 10 animals were used for each group. Induction of acetic acid-induced gastric ulcersAcetic acid-induced gastric ulcers were induced by luminal application of an acetic acid so...

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Cytoprotective and Ulcer Healing Properties of Prostaglandin E<sub>2</sub>, Colloidal Bismuth and Sucralfate in Rats

Cited by 56 publications

References 12 publications

Prostaglandin/Cyclooxygenase Pathway in Ghrelin-Induced Gastroprotection against Ischemia-Reperfusion Injury

Prostaglandin/Cyclooxygenase Pathway in Ghrelin-Induced Gastroprotection against Ischemia-Reperfusion Injury

An Overview of Acetic Acid Ulcer Models<br>—The History and State of the Art of Peptic Ulcer Research—

Changes in Gastric Function and Healing of Chronic Gastric Ulcers in Aged Rats

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Cytoprotective and Ulcer Healing Properties of Prostaglandin E<sub>2</sub>, Colloidal Bismuth and Sucralfate in Rats

Cited by 56 publications

References 12 publications

Prostaglandin/Cyclooxygenase Pathway in Ghrelin-Induced Gastroprotection against Ischemia-Reperfusion Injury

Prostaglandin/Cyclooxygenase Pathway in Ghrelin-Induced Gastroprotection against Ischemia-Reperfusion Injury

An Overview of Acetic Acid Ulcer Models<br>&mdash;The History and State of the Art of Peptic Ulcer Research&mdash;

Changes in Gastric Function and Healing of Chronic Gastric Ulcers in Aged Rats

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An Overview of Acetic Acid Ulcer Models<br>—The History and State of the Art of Peptic Ulcer Research—