Role of Gastric Mucosal Constitutive and Inducible Nitric Oxide Synthases in the Development of Stress-Induced Gastric Mucosal Lesions in Rats

Nishida, Keiji; Ohta, Yoshiji; Ishiguro, Isao

doi:10.1006/bbrc.1997.6972

Cited by 41 publications

(40 citation statements)

References 19 publications

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“…However, NO generated by iNOS may be involved in leukocyte adhesion, inflammatory cell infiltration and parenchyma cell dysfunction (Kobata et al, 2007;Lanteri et al, 2003), all have a deleterious influence on the gastric mucosal integrity. Experimental evidence also showed a drastic increase in iNOS activity and a decrease in cNOS activity in the gastric mucosal in rats with WIR stress (Nishida et al, 1997). In the present study, the alterations of cNOS and iNOS activity in the gastric mucosa induced by gastric I/R were significantly reversed by pretreatment with rutin, suggesting that the gastroprotective effect of rutin might be related to the maintenance of cNOS activity and inhibition of iNOS activity.…”

Section: Discussionsupporting

confidence: 72%

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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Section: Discussionsupporting

confidence: 72%

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

Liu

Gou

et al. 2013

Pharmaceutical Biology

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“…Previous studies have revealed that WIRE stress-induced gastric mucosal damage involves increased gastric juice secretion, gastric peristalsis, gastrocirculation disturbances in mucosal tissues, reduced prostaglandin levels, low turnover of gastric mucosa and NO-induced changes in gastric mucus cells (23)(24)(25). Among these patterns, NO-mediated regulation is particularly important as it is associated with host defense and inflammatory responses (26) and also plays a pivotal role in gastric mucosal protection against damage induced by ethanol, stress, endotoxins and drugs (27). NOS activity is particularly high in gastric tissues (28), where NO helps maintain gastric tissue integrity (29), controls gastromucosal-derived blood flow (30) and increases gastric mucus synthesis and secretion (28).…”

Section: Discussionmentioning

confidence: 99%

Protective effect of Acer mono Max. sap on water immersion restraint stress-induced gastric ulceration

Park

Son

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Acer mono Max. sap (AmMs) is called 'Gol-Li-Su' or 'Go-Lo-Soe' in Korean, which means 'water beneficial to the bones'. It is reported that the sap contains several types of minerals and sugars. In particular, the calcium concentration of the sap is 36.5 times higher than that of commercial mineral water. Apart from its anti-osteoporosis effect, no reports have addressed the biological activities of AmMs against degenerative diseases. In the present study, we investigated whether AmMs alleviates gastric ulcer-related symptoms in a stress-induced mouse model. To assess the effect of AmMs on gastric ulcer-like symptoms, we carried out a water immersion restraint (WIRE) test and found that AmMs has potential in alleviating gastric ulcers in a concentration-dependent manner. These results indicate that the nutritional factors of the sap mitigate the gastric ulcer-related symptoms caused by stress-induced gastric lesions in mice. AmMs-treated mice exhibited a significant decrease in the ulcer index as compared to those treated with omeprazole or L-arginine. To examine one potential mechanism underlying this effect, we performed reverse transcription-polymerase chain reaction to ascertain whether molecular markers were associated with the mitigation of the gastric lesions. Epithelial and/or tissue nitric oxide synthase (NOS) was assessed to determine whether or not the genes were down-regulated dose-dependently by the sap. The levels of these enzymes were found to be lower in the tissue samples treated with AmMs compared with the levels in the control samples. These findings collectively suggest that AmMs significantly protects the gastric mucosa against WIRE stress-induced gastric lesions, at least in part, by alleviating inducible NOS and/or neuronal NOS expression. IntroductionAcute gastric mucosal injury is a serious clinical problem worldwide. The symptoms cause severe gastric ulceritis and, with sustained exposure, eventually lead to gastric cancer. Researchers have developed many in vivo gastric lesion models: the water immersion restraint (WIRE) stress model, the indomethacin-induced model and the ethanol-induced model using animals (1). The WIRE model has previously been used to observe various aspects affecting the formation of and recovery from gastric mucosal lesions, including sulphydryls, prostaglandins, growth factors and polyamines (2). WIRE stress-induced gastric lesions have also been used to study the roles of cell death and gastric acid secretion in ulcerogenesis (3).In general terms, gastric lesions are a disorder of the gastric blockade, which typically protects against cavernous problems caused by hydrogen ions and other toxic substances generated in the lumen (4). One main component of the gastric barrier is gastric microcirculation; a disturbance in gastric mucosal perfusion results in the formation of lesions and ulcers, such as those that present in animal models of ischemic gastric lesions (5). Gastric blood flow is classically controlled by signaling molecules, such as prostagland...

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“…Reactive oxygen species (ROS) and nitric oxide ( • NO) generation, lipid peroxidation, and neutrophil infiltration in the gastric mucosal tissue play a critical role in the pathogenesis of WIRS-induced gastric mucosal lesions (2)(3)(4)(5).…”

mentioning

confidence: 99%

Effect of Dietary Vitamin E Supplementation on Liver Oxidative Damage in Rats with Water-Immersion Restraint Stress

Ohta

Yashiro

Ohashi

et al. 2015

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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Water-immersion restraint stress (WIRS), which is characterized with both psychological stress and physical stress, is widely used to induce reproducible stress ulcers in experimental animals (1). Reactive oxygen species (ROS) and nitric oxide ( • NO) generation, lipid peroxidation, and neutrophil infiltration in the gastric mucosal tissue play a critical role in the pathogenesis of WIRS-induced gastric mucosal lesions (2-5). Iwai et al. (6) have reported that, in rats with 6 h of WIRS, the level of liver lipid peroxide (LPO), which is generated via ROS, increases with concomitant increases in the levels of serum LPO and liver cell damage markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) activities and that pre-administration of gamazumi fruit juice or (2)-epigallocatechin gallate, each of which possesses antioxidant activity, for 2 wk attenuates all these stress-induced changes. Furthermore, the same authors have reported that not only an increase in LPO level but also decreases in superoxide dismutase (SOD) activity and reduced glutathione (GSH) level occur without changes in catalase and glutathione peroxidase activities in the liver of rats with 6 h of WIRS and that preadministration of gamazumi crude extract possessing antioxidant activity to rats with 6 h of WIRS for 2 wk attenuates the increased LPO level and the decreased SOD activity and GSH level in the liver (7). We have reported that, in the liver of rats exposed to WIRS over a 6-h period, cell damage occurs before the appearance of oxidative stress with disruption of antioxidant defense systems associated with decreased ascorbic acid (vitamin C) and GSH levels and SOD activity and enhanced lipid peroxidation, enhanced • NO generation, and neutrophil infiltration in the tissue, although the vitamin E level does not change in the liver tissue (8). We have also shown that a single pre-administration of l-ascorbic acid protects against oxidative damage in the liver of rats with 6 h of WIRS by attenuating disrupted antioxidant defense systems and enhanced lipid peroxidation, enhanced• NO generation, and neutrophil infiltration in Asaminami-ku, Hiroshima 731-0153, Japan (Received October 20, 2014) Summary We examined how dietary supplementation of vitamin E protects against liver oxidative damage in rats with water-immersion restraint stress (WIRS). Before WIRS exposure, rats received a normal diet (ND) or vitamin E-supplemented diet (VESD) (500 IU a-tocopherol/kg diet) at a mean dose of 15 g/animal/d for 4 wk. The two diet groups had serum transaminases and lactate dehydrogenase activities and adrenocorticotropic hormone, corticosterone, and glucose levels to a similar extent. VESD-fed rats had higher liver a-tocopherol concentrations and lower liver ascorbic acid, total coenzyme Q9 (CoQ9), reduced CoQ9, reduced CoQ10, and lipid peroxide (LPO) concentrations than ND-fed rats. When the two diet groups were exposed to 6 h of WIRS, the serum liver cell damage index enzyme activities incr...

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Role of Gastric Mucosal Constitutive and Inducible Nitric Oxide Synthases in the Development of Stress-Induced Gastric Mucosal Lesions in Rats

Cited by 41 publications

References 19 publications

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

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

Protective effect of Acer mono Max. sap on water immersion restraint stress-induced gastric ulceration

Effect of Dietary Vitamin E Supplementation on Liver Oxidative Damage in Rats with Water-Immersion Restraint Stress

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