Roles of Cyclooxygenase-2 and Prostacyclin/IP Receptors in Mucosal Defense against Ischemia/Reperfusion Injury in Mouse Stomach

Kotani, Tohru; Kobata, Atsushi; Nakamura, Eiji; Amagase, Kikuko; Takeuchi, Koji

doi:10.1124/jpet.105.093195

Cited by 26 publications

(44 citation statements)

References 43 publications

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“…Under the experimental conditions, the increased COX-2 expressed in the endothelial cells played a protective role against gastric injury induced by I/R (17,59). However, COX-1 has demonstrated inconsistent findings with regard to its role in gastric mucosa damaged by I /R with some studies assigning it a protective or neutral role (33,60) and another giving it an aggressive role (59).…”

Section: Discussionmentioning

confidence: 94%

“…The nucleotide sequences of the primers were as follows: β-actin: sense, 5' TTG TAA CCA ACT GGG ACG ATA TGG 3' and antisense, 5' GAT CTT GAT CTT CAT GGT GCT AGG 3'; COX-1: sense, 5' CTG CAT GTG GCT GTG GAT GTC ATC 3' and antisense, 5' GGT CTT GGT GAG GCA GAC CAG 3'; COX-2: sense, 5' TGA TGA CTG CCC AAC TCC CAT G 3' and anti-sense, 5' AAT GTT GAA GGT GTC CGG CAG C 3'. The primer sequences for β-actin, COX-1, and COX-2 were based on the sequences of their published cDNA (17,27). The polymerase chain reaction products were detected by electrophoresis on a 1.5% agarose gel in Tris-EDTAacetic acid buffer containing ethidium bromide.…”

Section: Cox Expression By Reverse Transcription Polymerase Chain Reamentioning

confidence: 99%

“…It forms prostaglandins (PGs) that contribute to the maintenance of mucosal integrity (13,14), while COX-2 is an inducible enzyme that is up-regulated by proinflammatory cells, like neutrophils and macrophages, and mediates inflammatory reactions and tumor growth (15,16). It has been reported that COX-2 is important for gastric mucosal defense and repair processes against I /R injuries (17,18). Recently, some reports have suggested that NADPH oxidase might regulate COX-2 expression and PG synthesis in vascular smooth muscle cells, esophageal adenocarcinoma cells, and macrophages (19 -22).…”

Section: Introductionmentioning

confidence: 99%

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Roles of NADPH Oxidase in Occurrence of Gastric Damage and Expression of Cyclooxygenase-2 During Ischemia/Reperfusion in Rat Stomachs

Nakagiri

Murakami

2009

J Pharmacol Sci

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Abstract. NADPH oxidase is an enzyme that converts molecular oxygen into reactive oxygen species, which cause severe damage in several organs. Cyclooxygenase (COX)-2 is an inducible enzyme that is important in gastric mucosal defense and repair processes. It is unclear whether NADPH oxidase is related to COX expression in the gastric mucosa, so we investigated the correlation. Under urethane anesthesia, a male Sprague Dawley rat stomach was mounted in an ex-vivo chamber, and ischemia/reperfusion (I/R) was performed through a cannula in the femoral vein. I /R significantly increased NADPH oxidase activity, H 2 O 2 production, and myeloperoxidase (MPO) activity. In contrast, ischemia alone clearly enhanced both NADPH oxidase activity and H 2 O 2 production but not MPO activity. Pretreatment with the NADPH oxidase inhibitor diphenylene iodonium (DPI) suppressed I/R-induced mucosal damage. On the other hand, the selective COX-2 inhibitor rofecoxib exhibited a tendency to enhance the severity of gastric damage induced by I /R, although the selective COX-1 inhibitor SC-560 and the nonselective COX inhibitor indomethacin had no effect. I/R also increased the expression of COX-2, and this increase was suppressed by pretreatment with DPI. These findings suggest that the increase in NADPH oxidase activity is involved in the occurrence of gastric mucosal damage induced by I /R and that this enzyme activity may be causally related to the upregulation of COX-2 during I /R.

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Section: Discussionmentioning

confidence: 94%

Section: Cox Expression By Reverse Transcription Polymerase Chain Reamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Roles of NADPH Oxidase in Occurrence of Gastric Damage and Expression of Cyclooxygenase-2 During Ischemia/Reperfusion in Rat Stomachs

Nakagiri

Murakami

2009

J Pharmacol Sci

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“…An aliquot of the reverse transcription reaction product served as a template for 35 PCR cycles consisting of 1-min denaturation at 94˚C, 0.5 min annealing at 56˚C, and 1-min extension at 72˚C in a thermal cycler. A portion of the PCR mixture was electrophoresed in a 1.5% agarose gel in Tris-EDTA-acetic acid buffer, and the gel was stained with ethidium bromide and photographed (20).…”

Section: Methodsmentioning

confidence: 99%

R-etodolac induces E-cadherin and suppresses colitis-related mouse colon tumorigenesis

Inoue

Murano²,

Yoda³

et al. 2010

Oncol Rep

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Abstract. Colorectal cancer is one of the most serious complications of ulcerative colitis (UC), and the risk of UCassociated neoplasia increases as the region and duration of the disease increase. Selective cyclooxygenase (COX)-2 inhibitors effectively diminish carcinogenesis in a murine UC model. However, this may exacerbate colitis. The selective COX-2 inhibitor etodolac is marketed as a racemic mixture of the R-and S-enantiomers. The biochemical and pharmacological effects of etodolac are caused by the S-enantiomer, while the R-enantiomer lacks COX-inhibitory activity. In this study, we evaluated the effect of R-etodolac on colitisrelated mouse colon tumorigenesis. The mice received 1,2-dimethlhydrazine (DMH), and then chronic colitis was induced by administration of two cycles of DSS (each cycle: 3% DSS for 7 days followed by distilled water for 14 days). The mice were sacrificed 28 days after the completion of both cycles. Mice were divided into the following groups: group A served as a disease control; group B received a low (2-mg/kg) dose of R-etodolac every 3 days during the entire period; group C received a high (10-mg/kg) dose of R-etodolac on the same schedule as group B; and group D served as a normal control. Administration of R-etodolac decreased the disease activity index during the DSS administration cycle. The mean number of tumors was 17.8, 15.2, 6.0, and 0 in groups A-D, respectively. In group C, R-etodolac significantly suppressed the occurrence of neoplasia (p<0.05). Although R-etodolac treatment did not affect COX-2 expression, it significantly enhanced expression of E-cadherin in both neoplastic lesions and background mucosa (i.e., lesionfree colon). Thus, administration of R-etodolac exerts a suppressive effect on the development of neoplasia in a murine model of DSS-induced colitis without exacerbation of the colitis. These results suggest that R-etodolac could be useful in the prevention of UC-associated neoplasia.

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“…Some experimental studies have demonstrated that free radicals, lipid peroxidation and neutrophils infiltration in gastric mucosa play important roles in the pathogenesis of acute gastric lesions induced by I/R (Andrews et al, 1994a;Kitahora & Guth, 1987). Moreover, it has been demonstrated that various other factors, such as prostaglandins and nitric oxide (NO), play pathogenic roles in these gastric lesions (Kotani et al, 2006;Naito et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Protective effect of rutin against acute gastric mucosal lesions induced by ischemia-reperfusion

Liu

Gou

et al. 2013

Pharmaceutical Biology

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Context: Rutin, a flavonoid commonly present in onions, apples and tea, has been suggested to have a variety of pharmacological activities, including immunomodulator, anti-inflammatory and antioxidant activities. Objectives: The present study was to examine the protective effects of rutin on gastric mucosal damage induced by gastric ischemia-reperfusion (I/R) in rats. Materials and methods: Rutin (50, 100, 200 mg/kg) was administered intragastrically for five consecutive days before ischemia. Sixty minutes after the last administration of rutin, under anesthesia, the celiac artery was clamped for 30 min, and then the clamp was removed for 60 min reperfusion. After reperfusion, the stomach was removed for biochemical and histological examinations. Results: As compared with the I/R group (116.7 AE 21.5), administration of rutin at doses of 50, 100 and 200 mg/kg significantly prevented the increase of gastric mucosal injury index induced by gastric I/R (73.4 AE 14.8, 65.9 AE 9.6 and 26.9 AE 5.7, respectively). ED 50 value was 138.7 mg/kg. Moreover, rutin at doses of 50, 100 and 200 mg/kg showed an inhibition on the increased myeloperoxidase (24.6, 41.3 and 53.1% reduction) activity and malondialdehyde levels (27.4, 40.3 and 50.7% reduction) in gastric mucosa. Also, the elevation of inducible NO synthase (iNOS) activity as well as the decrease of constitutive NO synthase (cNOS) in the gastric mucosa were significantly prevented by rutin pretreatment. Conclusion: These results suggested that rutin has a protective effect against gastric mucosal injury induced by gastric I/R and that the gastroprotection was related to the NOS/NO pathway and its antioxidant activity.

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Roles of Cyclooxygenase-2 and Prostacyclin/IP Receptors in Mucosal Defense against Ischemia/Reperfusion Injury in Mouse Stomach

Cited by 26 publications

References 43 publications

Roles of NADPH Oxidase in Occurrence of Gastric Damage and Expression of Cyclooxygenase-2 During Ischemia/Reperfusion in Rat Stomachs

Roles of NADPH Oxidase in Occurrence of Gastric Damage and Expression of Cyclooxygenase-2 During Ischemia/Reperfusion in Rat Stomachs

R-etodolac induces E-cadherin and suppresses colitis-related mouse colon tumorigenesis

Protective effect of rutin against acute gastric mucosal lesions induced by ischemia-reperfusion

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