Helicobacter pylori infection potentiates aspirin induced gastric mucosal injury in Mongolian gerbils

Yoshida, Norimasa; Sugimoto, Naohito; Hirayama, Fumihiro; Nakamura, Y.; Naito, Yuji; Yoshikawa, Toshikazu

doi:10.1136/gut.50.5.594

Cited by 31 publications

(25 citation statements)

References 33 publications

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“…Several studies have demonstrated that NSAIDs enhance H. pylori-induced gastric mucosal inflammation and injury [7-10, 28, 43, 44]-for example, Takahashi et al reported that NS-398, a COX-2-specific inhibitor, and indomethacin, a dual COX inhibitor, promoted H. pylori-induced neutrophil infiltration and lymphoid follicle formation [44]; Tanigawa et al showed that inhibition of COX-1 (by use of SC-560) or COX-2 (by use of NS-398) enhanced neutrophil infiltration into gastric mucosa in H. pylori-infected mice [28]; and Yoshida et al reported that H. pylori infection potentiated aspirin-induced gastric mucosal injury in Mongolian gerbils [10]. However, other studies have shown that NSAIDs have no effect or even protective effects on H. pylori-induced gastritis-Kim et al reported that indomethacin and NS-398 decreased gastric inflammation induced by H. pylori infection in mice [11], and, in a clinical study conducted by Scheiman et al, rofecoxib, a COX-2 inhibitor, did not significantly affect gastritis scores [12].…”

Section: Discussionmentioning

confidence: 98%

“…Helicobacter pylori infection is a major cause of chronic gastritis, peptic ulceration, and gastric carcinoma [3]. Studies have shown that COX-2 is induced in gastric mucosa during H. pylori infection [4][5][6] and that NSAIDs enhance H. pylori-induced gastric inflammation and ulceration [7][8][9][10][11][12]. However, the role played by COX-2 in H. pylori-induced gastric inflammation is not entirely understood.…”

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confidence: 99%

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Effects of Cyclooxygenase‐1 and ‐2 Gene Disruption onHelicobacter pylori–Induced Gastric Inflammation

Xia

Chen

et al. 2006

J INFECT DIS

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Effects of Cyclooxygenase‐1 and ‐2 Gene Disruption onHelicobacter pylori–Induced Gastric Inflammation

Xia

Chen

et al. 2006

J INFECT DIS

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“…These data suggest that lipid peroxida-tion plays a significant role in the pathogenesis of the gastric mucosal injury induced by indomethacin, similar to experimental gastric injuries produced by stress, 6,7 ischemia-reperfusion, 8 and Helicobacter pylori infection. 9 Although the measurement of TBA-reactive substances is not specific for lipid peroxides, it is one of the oldest and most frequently used methods for measuring the peroxidation of fatty acid, cellular membranes, and food products. The increase in TBA-reactive substances in the gastric mucosa after indomethacin administration has been demonstrated by similar animal studies 10-14 and human biopsy samples.…”

Section: Oxidative Stress In Indomethacin-induced Gastric Mucosal Injmentioning

confidence: 99%

Oxidative stress involvement and gene expression in indomethacin-induced gastropathy

Naito

Yoshikawa

2006

Redox Report

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It has been proposed that neutrophil- and oxygen radical-dependent microvascular injuries are important prime events that lead to gastric mucosal injury induced by indomethacin. Reactive oxygen species (ROS) produced by activated neutrophils after indomethacin treatment cause gastric mucosal injury via ROS-mediated oxidation of important biomolecules such as lipid, protein, and DNA. In addition, it has been revealed that indomethacin-induced gastric mucosal injury occurs via gastric epithelial cell apoptosis. However, there is little known about the mechanism of indomethacin-triggered cellular response and apoptotic signaling in gastric mucosal cells. In the present study, we summarize the evidence that supports the involvement of oxidative stress and apoptosis in indomethacin-induced gastropathy, and review the gene expression profiles of gastric epithelial cells after indomethacin treatment determined by DNA microarray analysis.

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“…Animal models could be useful to address this issue. For example, some reports have demonstrated that NSAID-induced gastric lesions in mongolian gerbils are exacerbated by infection with H. pylori (7)(8)(9), although the molecular mechanism governing this exacerbation is unclear.…”

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confidence: 99%

Suppression of Expression of Endoplasmic Reticulum Chaperones by Helicobacter pylori and Its Role in Exacerbation of Non-steroidal Anti-inflammatory Drug-induced Gastric Lesions

Namba

Hoshino

Suemasu

et al. 2010

Journal of Biological Chemistry

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Both the use of non-steroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, and infection with Helicobacter pylori are major causes of gastric ulcers. Although some clinical studies suggest that infection with H. pylori increases the risk of developing NSAID-induced gastric lesions, the molecular mechanism governing this effect is unknown. We recently found that in cultured gastric cells, expression of endoplasmic reticulum (ER) chaperones (such as 150-kDa oxygenregulated protein (ORP150) and glucose-regulated protein 78 (GRP78)) is induced by NSAIDs and confers protection against NSAID-induced apoptosis, which is important in the development of NSAID-induced gastric lesions. In this study we have found that co-culture of gastric cells with H. pylori suppresses the expression of ER chaperones. This suppression was regulated at the level of transcription and accompanied by a reduction in the level of activating transcription factor 6 (ATF6), one of the transcription factors for ER chaperone genes. In vivo, inoculation of mice with H. pylori suppressed the expression of ER chaperones at gastric mucosa both with and without administration of indomethacin. Inoculation with H. pylori also stimulated formation of indomethacin-induced gastric lesions and mucosal cell death. In addition, we found that heterozygous ORP150-deficient mice are sensitive to the development of indomethacin-induced gastric lesions and mucosal cell death. The results of this study suggest that H. pylori exacerbates NSAID-induced gastric lesions through suppression of expression of ER chaperones, which stimulates NSAID-induced mucosal cell death.The balance between aggressive and defensive factors determines whether gastric ulcers develop. The gastric mucosa is challenged by a variety of aggressive factors, and of these, both non-steroidal anti-inflammatory drugs (NSAIDs) 2 and Helicobacter pylori are major causes of gastric lesions. Therefore, an important question is whether infection with H. pylori increases the risk of developing NSAID-induced gastric lesions (in other words, if eradication of H. pylori would reduce the risk of developing NSAID-induced gastric lesions). Recent clinical studies suggest that infection with H. pylori increases the risk of developing NSAID-induced gastric lesions (1-4); however, some studies have shown the opposite effect (5, 6). Animal models could be useful to address this issue. For example, some reports have demonstrated that NSAID-induced gastric lesions in mongolian gerbils are exacerbated by infection with H. pylori (7-9), although the molecular mechanism governing this exacerbation is unclear.An inhibitory effect of NSAIDs on cyclooxygenase (COX) activity and the resulting decrease in the gastric level of prostaglandins (PGs), especially PGE 2 , was believed to be the only explanation for the gastric side effects of NSAIDs because PGE 2 is a strong protective factor for gastric mucosa (10). However, the increased incidence of gastrointestinal lesions and the decrease in PG levels induced by NSA...

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Helicobacter pylori infection potentiates aspirin induced gastric mucosal injury in Mongolian gerbils

Cited by 31 publications

References 33 publications

Effects of Cyclooxygenase‐1 and ‐2 Gene Disruption onHelicobacter pylori–Induced Gastric Inflammation

Effects of Cyclooxygenase‐1 and ‐2 Gene Disruption onHelicobacter pylori–Induced Gastric Inflammation

Oxidative stress involvement and gene expression in indomethacin-induced gastropathy

Suppression of Expression of Endoplasmic Reticulum Chaperones by Helicobacter pylori and Its Role in Exacerbation of Non-steroidal Anti-inflammatory Drug-induced Gastric Lesions

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