Mucosal acid causes gastric mucosal microcirculatory disturbance in nonsteroidal anti-inflammatory drug-treated rats

Funatsu, Toshiyuki; Chono, Koji; Hirata, Tetsuya; Keto, Yoshihiro; Kimoto, Aishi; Sasamata, Masao

doi:10.1016/j.ejphar.2006.10.023

Cited by 26 publications

(21 citation statements)

References 22 publications

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“…The primary pathology of NSAID-induced acute gastric mucosal damage is likely to be mucosal lesions due to inhibition of cyclooxygenase that prevents prostaglandin biosynthesis which in turn inhibits the release of mucus (Kauffman, 1989;Hudson et al, 1992), and reduction in gastric mucosal damage is likely to be mucosal lesions due to ischemia. The main mechanism by which NSAIDs reduce gastric mucosal blood flow is thought to be inhibition of COX-1 (Funatsu et al, 2007). This inhibition leads to a deficiency in endogenous prostaglandin E 2 and PGI 2 which in turn cause microcirculatory disturbances in the gastric mucosa (Shorrock & Rees, 1989).…”

Section: Discussionmentioning

confidence: 99%

Gastric antiulcer, antisecretory and cytoprotective properties of celery (Apium graveolens) in rats

Al‐Howiriny

Alsheikh

Alqasoumi

et al. 2010

Pharmaceutical Biology

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Section: Discussionmentioning

confidence: 99%

Gastric antiulcer, antisecretory and cytoprotective properties of celery (Apium graveolens) in rats

Al‐Howiriny

Alsheikh

Alqasoumi

et al. 2010

Pharmaceutical Biology

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“…Therefore, we believe that to prevent aspirin-induced gastric mucosal injury, the 24-h intragastric pH should be maintained at higher than 4 by concomitant treatment with a PPI. The role of gastric acid in the pathogenesis of NSAIDinduced gastric mucosal injury was intensively studied by Funatsu et al [23]. They studied the gastric mucosal microcirculation in rats treated with diclofenac in the absence and presence of acid.…”

Section: Discussionmentioning

confidence: 99%

Relationship Between Low-Dose Aspirin-Induced Gastric Mucosal Injury and Intragastric pH in Healthy Volunteers

et al. 2009

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“…Studies using selective COX-1 or COX-2 inhibitors have indicated that the gastric ulcerogenic properties of NSAIDs are caused by inhibition of both COX-1 and COX-2 (Wallace et al, 2000;Tanaka et al, 2001). However, several reports suggest that other elements such as free radicals, disturbances of microcirculation, and hypermotility may be involved in the pathogenic mechanisms (Naito and Yoshikawa, 2006;Funatsu et al, 2007;Takeuchi, 2012). Furthermore, it has been reported that other risk factors, including diabetes and concomitant use of other agents, aggravate gastric lesions induced by NSAIDs (Pradeepkumar Singh et al, 2011;Takeuchi et al, 2011;Kwiecien et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Acetaminophen on Ibuprofen-Induced Gastric Mucosal Damage in Rats with Associated Suppression of Matrix Metalloproteinase

Fukushima

Monoi

Mikoshiba

et al. 2014

J Pharmacol Exp Ther

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause gastric mucosal damage as a side effect. Acetaminophen, widely used as an analgesic and antipyretic drug, has gastroprotective effects against gastric lesions induced by absolute ethanol and certain NSAIDs. However, the mechanisms that underlie the gastroprotective effects of acetaminophen have not yet been clarified. In the present study, we examined the role and protective mechanism of acetaminophen on ibuprofen-induced gastric damage in rats. Ibuprofen and acetaminophen were administered orally, and the gastric mucosa was macroscopically examined 4 hours later. Acetaminophen decreased ibuprofeninduced gastric damage in a dose-dependent manner. To investigate the mechanisms involved, transcriptome analyses of the ibuprofen-damaged gastric mucosa were performed in the presence and absence of acetaminophen. Ingenuity pathway analysis (IPA) software revealed that acetaminophen suppressed the pathways related to cellular assembly and inflammation, whereas they were highly activated by ibuprofen. On the basis of gene classifications from the IPA Knowledge Base, we identified the following five genes that were related to gastric damage and showed significant changes in gene expression: interleukin-1b (IL-1b), chemokine (C-C motif) ligand 2 (CCL2), matrix metalloproteinase-10 (MMP-10), MMP-13, and FBJ osteosarcoma oncogene (FOS). Expression of these salient genes was confirmed using real-time polymerase chain reaction. The expression of MMP-13 was the most reactive to the treatments, showing strong induction by ibuprofen and suppression by acetaminophen. Moreover, MMP-13 inhibitors decreased ibuprofeninduced gastric damage. In conclusion, these results suggest that acetaminophen decreases ibuprofen-induced gastric mucosal damage and that the suppression of MMP-13 may play an important role in the gastroprotective effects of acetaminophen.

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Mucosal acid causes gastric mucosal microcirculatory disturbance in nonsteroidal anti-inflammatory drug-treated rats

Cited by 26 publications

References 22 publications

Gastric antiulcer, antisecretory and cytoprotective properties of celery (Apium graveolens) in rats

Gastric antiulcer, antisecretory and cytoprotective properties of celery (Apium graveolens) in rats

Relationship Between Low-Dose Aspirin-Induced Gastric Mucosal Injury and Intragastric pH in Healthy Volunteers

Protective Effects of Acetaminophen on Ibuprofen-Induced Gastric Mucosal Damage in Rats with Associated Suppression of Matrix Metalloproteinase

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