Effect of geranylgeranylacetone on aspirin-induced changes in gastric glycoproteins.

Oketani, Kiyoshi; Murakami, Manabu; Fujisaki, Hideaki; Wakabayashi, Tsuneo; Hotta, Kyoko

doi:10.1254/jjp.33.593

Cited by 37 publications

(15 citation statements)

References 11 publications

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“…Previous stud ies on its action on the gastric mucosa showed that TPA mitigated the reduction in mucosal blood flow in restrained water im mersion stress [7], preventing the decrease in gastric glycoproteins [25] and stimulating endogenous bicarbonate secretion [26], The administration of TPA in the present study inhibited decreases in EC values. In this connection, when gastric mucosal injury is induced by hydrochloric acid, the conver sion of ATP to ADP by ATPase is increased and the conversion of ATP to cAMP by ade nylate cyclase diminishes, while prostacy clins, which have a mucosal protective ef fect, enhance both of these transformations and therefore cause a drop in the ATP/ADP ratio as well as in the value of the EC [27], On the other hand, cimetidine confers cytoprotection by retarding both of these trans formations and thereby inhibits decreases in the ATP/ADP ratio and the EC.…”

Section: Discussionsupporting

confidence: 51%

Changes in Gastric Mucosal Content of Adenosine, Xanthine and Hypoxanthine Induced by Restrained Water Immersion Stress: Antiulcer Effects of Tetraprenylacetone

Itoh

Suzuki²,

Matsubara³

et al. 1991

Digestion

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The purpose of this study was to clarify the involvement of adenine nucleotide metabolism and substrates of the xanthine-xanthine oxidase system as the source of oxygen free radicals in a rat model of restrained water immersion stress ulceration. The gastric mucosal concentrations of adenine-5’-triphosphate (ATP), adenine-5´-diphosphate (ADP), adenine-5´-monophosphate (AMP) and thiobarbituric-acid (TBA)-reactant substances were measured after 4, 8 and 12 h restrained water immersion stress. The gastric mucosal concentrations of the nucleoside adenosine, the purine bases xanthine and hypoxanthine, and the final metabolic product uric acid, were measured after 4 h of restrained water immersion stress. The concentrations of ATP diminished significantly after 4, 8 and 12 h of restrained water immersion stress. However, the observed stress-induced changes in ADP were not significant. AMP concentrations increased significantly after 4, 8 and 12 h of stress. The adenylate pool (ATP + ADP + AMP) dropped significantly from the prestress value after 4, 8 and 12 h of stress, and the concomitant energy charge (EC = ATP + 0.5 ADP/ATP + ADP+ AMP) decreased significantly after 4 and 8 h of stress compared with the prestress value. Gastric mucosal concentrations of TBA-reactant substances displayed a significant increase after 4 h of stress, and remained unchanged after 8 and 12 h of stress from the level after 4 h. Four hours of restrained water immersion stress induced an increase in adenosine and uric acid concentrations and a decrease in the hypoxanthine concentration of the gastric mucosa. In addition, the protective effect of tetraprenylacetone (TPA) with respect to energy metabolism impairment and the production of active oxygen was investigated. Administration of TPA inhibited the ulcer formation, the reduction in energy charge values after 4 and 8 h of restrained water immersion stress and the increase in TBA-reactant substances after 4 h of restrained water immersion stress. TPA administration also inhibited the increase in adenosine and uric acid concentrations as well as the decrease in the hypoxanthine concentrations of the gastric mucosa caused by restrained water immersion stress. These results suggest that TPA exerted a cytoprotective action by virtue of its ability to counteract the adenine nucleotide metabolism and its action on the substrates of the xanthine-xanthine oxidase system.

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Section: Discussionsupporting

confidence: 51%

Changes in Gastric Mucosal Content of Adenosine, Xanthine and Hypoxanthine Induced by Restrained Water Immersion Stress: Antiulcer Effects of Tetraprenylacetone

Itoh

Suzuki²,

Matsubara³

et al. 1991

Digestion

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“…There have been numerous reports indicating that GGA exerts its mucoprotective effects through the induction of HSP and the stimulation of mucin secretion in the gastric mucosa [9,10,11,24,25,26]. GGA is an acyclic polyisoprenoid compound that protects against gastric injury induced by cold or water-immersion restraint stresses, and by non-steroidal anti-inflammatory drugs [10,27,28].…”

Section: Discussionmentioning

confidence: 99%

“…Geranylgeranylacetone (GGA) is a mucoprotective drug developed in Japan that has been shown to not only induce mucous secretion in the stomach, but to also upregulate heat shock proteins (HSPs) in gastric epithelial cells [11,12,13,14]. GGA is now widely used to treat patients with gastric ulcers or chronic gastritis regardless of H. pylori infection, both in Japan and other Asian countries [15,16,17,18].…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Effectiveness of Geranylgeranylacetone with Cimetidine in Gastritis Patients with Dyspeptic Symptoms and Gastric Lesions: A Randomized, Double-Blind Trial in Japan

et al. 2007

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Background and Aim: Controversy remains regarding the treatment of choice for chronic gastritis patients with dyspeptic symptoms when Helicobacter pylori eradication is not indicated or fails for their gastric lesions. A multicenter, randomized, double-blind trial was performed to compare the effectiveness of geranylgeranylacetone (GGA), a mucoprotective drug, against cimetidine (CIT), an H₂-receptor antagonist, on the treatment of erosions and petechial hemorrhage in H. pylori-infected patients with dyspeptic symptoms. Methods: 128 H. pylori-positive gastritis patients with mucosal erosions and/or petechial hemorrhage were randomized to receive 150 mg GGA t.i.d. or 400 mg CIT b.i.d. for 2 weeks. Improvement and cure rates on endoscopic findings, symptom disappearance rates, and changes in mucosal neutrophil infiltration were compared. Results: Endoscopic improvement rates were significantly higher in the GGA group (n = 50) than in the CIT group (n = 54; 86.0 vs. 64.8%, p = 0.014). Endoscopic cure rates were also significantly higher for GGA than for CIT (80.0 vs. 55.6%, p = 0.012). Symptom disappearance rates were 52.0% for GGA and 42.6% for CIT, but the difference was not significant. There was also no significant difference in mucosal neutrophil infiltration between the groups. Conclusion: GGA treatment appears to be more effective than CIT for chronic gastritis-associated erosion and petechial hemorrhage.

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“…Thirty minutes later, all rats were given intragastrically 1 ml o f absolute ethanol and after 30 min the animals were killed by decapitation and their stomachs removed. The dose of GGA used in the experiments was chosen based on earlier stud ies which demonstrated that GGA at 200 mg/kg was most effective in the prevention of gastric mucosal damage in rats [12,15,16].…”

Section: Animal Preparationmentioning

confidence: 99%

Protection against Alcohol-Induced Gastric Mucosal Injury by Geranylgeranylacetone: Effect of Indomethacin

et al. 1988

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The mechanism of gastric mucosal protection by an antiulcer agent, geranylgeranylacetone (GGA), against ethanol-induced injury was investigated. The experiments were conducted with groups of rats with and without intraperitoneal indomethacin pretreatment. Animals received intragastrically either a dose of GGA (200 mg/kg) or a vehicle, followed 30 min later by 1 ml of absolute ethanol. The rats were sacrificed after 30 min and the gastric mucosa was subjected to macroscopic and histologic assessment and the measurements of adherent mucus, its dimension and chemical composition. In the absence of GGA, ethanol produced advanced macroscopic necrosis ( > 38%) and the extensive necrotic lesions were visible upon histologic examination. Pretreatment with GGA significantly reduced (p < 0.001) the extent and depth of mucosal necrotic lesions caused by ethanol, and this protection was not thwarted by indomethacin. Evaluation of the adherent mucus and its dimension by Alcian blue uptake and inverted microscope technique revealed that GGA was also capable of preventing the untoward effect of indomethacin on the adherent gastric mucus gel and its thickness. Results of chemical analyses established that in the absence of GGA indomethacin caused an increase in mucus protein (15%) and a decrease in its covalently bound fatty acids (67%) and lipids (36%). The decrease in lipids was particularly reflected in the content of phospholipids. Indomethacin, however, had no apparent effect on the composition of gastric mucus elaborated in the presence of GGA. The results suggest that gastric mucosal protective action of GGA is not mediated by endogenous prostaglandins but rather appears to involve the metabolism of mucosal lipids.

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Effect of geranylgeranylacetone on aspirin-induced changes in gastric glycoproteins.

Cited by 37 publications

References 11 publications

Changes in Gastric Mucosal Content of Adenosine, Xanthine and Hypoxanthine Induced by Restrained Water Immersion Stress: Antiulcer Effects of Tetraprenylacetone

Changes in Gastric Mucosal Content of Adenosine, Xanthine and Hypoxanthine Induced by Restrained Water Immersion Stress: Antiulcer Effects of Tetraprenylacetone

Comparison of the Effectiveness of Geranylgeranylacetone with Cimetidine in Gastritis Patients with Dyspeptic Symptoms and Gastric Lesions: A Randomized, Double-Blind Trial in Japan

Protection against Alcohol-Induced Gastric Mucosal Injury by Geranylgeranylacetone: Effect of Indomethacin

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