Insulin-like growth factor-I reduces stress-induced gastric mucosal injury by inhibiting neutrophil activation in mice

ObjectiveWe previously reported that activated neutrophils are critically involved in the development of stress-induced gastric mucosal injury in mice. Caspase activation plays an important role in the pathogenesis of tissue injury by activating neutrophils through an increase in the expression of endothelial monocyte-activating polypeptide-II (EMAP-II), a chemoattractant for neutrophils. Since insulin-like growth factor-I (IGF-I) inhibits caspase activation, it is possible that IGF-I reduces gastric mucosal injury by inhibiting neutrophil activation. In the present study, we examined this possibility in mice subjected to water-immersion restraint stress (WIR).DesignMice were intraperitoneally administered with IGF-I or vehicle before being subjected to WIR. Gastric mucosal injury, gastric myeloperoxidase (MPO) activity, the immunofluorescence intensity of MPO, caspase-3 activity, number of apoptotic cells, EMAP-II expression and activation of Akt and glycogen synthase kinase-3β (GSK-3β) in gastric mucosa were determined in mice subjected to WIR. Neutropenia was induced by administration of methotrexate (MTX).ResultsAdministration of IGF-I at dosages higher than 200 μg/kg significantly reduced gastric mucosal injury and inhibited increases in gastric MPO activities after 8 h of WIR. Administration of MTX also reduced the gastric mucosal injury as well as inhibiting increases in both gastric mucosal MPO activities and circulating neutrophil number. IGF-I (500 μg/kg) inhibited the increases in both gastric MPO activity and the immunofluorescence intensity of MPO observed in the gastric mucosa, but had no effect on the increase in circulating neutrophil number after 8 h of WIR. It also markedly blunted WIR-induced increases in caspase-3 activities and the number of apoptotic cells in the gastric mucosa after 8 h of WIR. Gastric expression of EMAP-II was markedly increased at 8 h after starting WIR and this increase was inhibited by IGF-I administration. Administration of IGF-I enhanced WIR-induced phosphorylation of Akt and GSK-3β in the gastric mucosa.ConclusionThese observations indicate that IGF-I reduces stress-induced gastric mucosal injury by inhibiting gastric accumulation of neutrophils through inhibition of caspase-3-mediated EMAP-II activation. Furthermore, IGF-I might inhibit caspase-3 activation through Akt/GSK-3β signaling.     

Inhaled neutrophil elastase inhibitor reduces oleic acid-induced acute lung injury in rats

RationaleNeutrophil elastases (NE) play an important role in the pathogenesis of acute lung injury (ALI). NE activities are significantly increased in serums and lungs of patients or animals with ALI. Intravenous infusion (IV) of Sivelestat, an NE inhibitor, can reduce ALI. Through inhalation, drugs reach lungs directly and in high concentration. We hypothesized that inhaled Sivelestat would alleviate oleic acid (OA)-induced ALI in rats.MethodsRats were anesthetized and mechanically ventilated, and then ALI was induced by OA injection. One hour later, the animals were randomized to receive either Sivelestat (3 mg/kg/h) or saline inhalation. The effect of Sivelestat IV (3 mg/kg/h) was also investigated. All animals were ventilated and observed for 6 h.ResultsOA injection increased NE activities in lung tissues and serums. The increase of NE activities in lung tissues and serums markedly reduced by 77%, and 29%, respectively, by the inhalation of Sivelestat; and 53.8%, and 80%, respectively, by Sivelestat IV. Additionally, inhaled Sivelestat resulted in ameliorated lung injury by reducing edema and infiltration of neutrophils in the lung, improved oxygenation and survival.ConclusionsAn over increased NE activity in lungs may play a vital effect in the pathogenesis of OA-induced ALI in rats. Topical application of nebulized Sivelestat, an NE inhibitor, may reduce OA-induced ALI in rats. Sivelestat inhalation can be developed as a novel treatment for ALI.     

Nitric oxide-mediated gastric hyperemia decreases ethanol-induced gastric mucosal injury in uremic rats

We investigated whether the recently described endothelium-derived nitric oxide-mediated gastric hyperemia in the uremic rat protects the gastric mucosa against ethanol injury. Uremia was induced by subtotal nephrectomy. Basal gastric mucosal blood flow, measured by a hydrogen gas clearance technique, was significantly higher in uremic than control rats. Continuous intragastric perfusion with 40% ethanol produced significantly less gross and histological lesions in uremic than in control rats. The administration of 3 mg/kg ofN ^W-nitro-l-arginine methyl ester, a specific inhibitor of nitric oxide biosynthesis, decreased resting gastric mucosal blood flow to control levels in uremic rats, but had no effect on basal gastric blood flow in control rats. This pretreatment with the inhibitor of nitric oxide biosynthesis increased 40% ethanol-induced gastric mucosal lesions in uremic rats to the same level as that observed in control rats, but had no effect on lesions in control rats. In conclusion, this study suggests that in the uremic rat, gastric hyperemia, mediated by increased endothelium-derived nitric oxide, attenuates ethanol-induced gastric mucosal injury.Dr. Enrique Quintero is the recipient of a Fogarty International Fellowship Award (N.I.H.) (1 FO5 TW04443-01) and a Grant from Consejería de Educación, Cultura y Deportes of the Canary Islands Autonomous Government. This work was also supported by Veterans Administration Research Funds.     

Increased susceptibility of aging gastric mucosa to injury and delayed healing: Clinical implications

In this editorial we comment on the article by Fukushi K et al published in the recent issue of the World Journal of Gastroenterology 2018; 24(34): 3908-3918. We focus specifically on the mechanisms of the anti-thrombotic action of aspirin, gastric mucosal injury and aging-related increased susceptibility of gastric mucosa to injury. Aspirin is widely used not only for the management of acute and chronic pain and arthritis, but also importantly for the primary and secondary prevention of cardiovascular events such as myocardial infarcts and strokes. Clinical trials have consistently shown that antiplatelet therapy with long term, low dose aspirin (LDA) - 75 to 325 mg daily, dramatically reduces the risk of non-fatal myocardial infarcts, stroke and mortality in patients with established arterial diseases. However, such treatment considerably increases the risk of gastrointestinal (GI) ulcerations and serious bleeding by > 2-4 fold, especially in aging individuals. This risk is further increased in patients using LDA together with other antiplatelet agents, other nonsteroidal anti-inflammatory agents (NSAIDs) and/or alcohol, or in patients with Helicobacter pylori (H. pylori) infection. Previous studies by our group and others have demonstrated prominent structural and functional abnormalities in gastric mucosa of aging individuals (which we refer to as aging gastric mucosa or “aging gastropathy”) compared to the gastric mucosa of younger individuals. Aging gastric mucosa has impaired mucosal defense, increased susceptibility to injury by a variety of noxious agents such as aspirin, other NSAIDs and ethanol, and delayed and impaired healing of injury. The mechanism underlying these abnormalities of aging gastric mucosa include reduced mucosal blood flow causing hypoxia, upregulation of PTEN, activation of pro-apoptotic caspase-3 and caspase-9, and reduced survivin (anti-apoptosis protein), importin-α (nuclear transport protein), vascular endothelial growth factor, and nerve growth factor. The decision regarding initiation of a long-term LDA therapy should be made after a careful consideration of both cardiovascular and GI risk factors. The latter include a previous history of GI bleeding and/or ulcers, age ≥ 70, male gender, concurrent use of other NSAIDs, alcohol consumption and H. pylori infection. Furthermore, the incidence of GI ulcers and bleeding can be reduced in patients on long term LDA treatment by several measures. Clinicians treating such patients should test for and eradicate H. pylori, instruct patients to avoid alcohol and non-aspirin NSAIDs, including cyclooxygenase-2-selective NSAIDs, and prescribe proton pump inhibitors in patients on LDA therapy. In the future, clinicians may be able to prescribe one of several potential new drugs, which include aspirin associated with phosphatidylcholine (PL2200), which retains all property of aspirin but reduces by approximately 50% LDA-induced GI ulcerations.     

Rebamipide prevents delay of acetic acid-induced gastric ulcer healing caused by Helicobacter pylori infection in Mongolian gerbils

In this study, we examined the effect of rebamipide, a mucoprotective drug, on gastric ulcer healing in Mongolian gerbils infected with H. pylori. Male Mongolian gerbils were inoculated with H. pylori or vehicle alone 12 hr after the production of an acetic acid-induced gastric ulcer. On day 5, the gerbils inoculated with H. pylori were divided into three groups and fed rebamipide-containing diet (0.038%, 60 mg/kg, or 0.0038%, 6 mg/kg), or standard laboratory chow. The gerbils inoculated with the vehicle were fed standard laboratory chow throughout the experiment. The gerbils were killed on day 5, 15, or 30 after ulcer production, and removed stomachs were subjected to calculation of ulcer size, culture for H. pylori, and measurement of myeloperoxidase activity, a marker for neutrophil infiltration, in ulcerated tissue. Apoptotic and proliferating cells of gastric epithelium in ulcer margins were detected by the in situ DNA nick end-labeling method and immunohistochemical staining for 5-bromo-2'-deoxyuridine (BrdU), respectively. Rebamipide did not affect colonization levels of H. pylori. Infection with H. pylori did not affect ulcer size by day 5 but significantly delayed ulcer healing by days 15 and 30, accompanied by an increase in the number of apoptotic cells, a decrease in the number of BrdU-positive cells, and an increase in myeloperoxydase activity. Rebamipide prevented delay of ulcer healing and abolished these effects of H. pylori on cell kinetics and neutrophil infiltration. In conclusion, rebamipide may prevent the delay of acetic acid-induced gastric ulcer healing caused by H. pylori through modulating cell kinetics and inhibiting neutrophil infiltration.     

瑞巴派特对门脉高压性胃病胃黏膜中瘦素表达的影响

目的:观察瑞巴派特对门脉高压性胃病胃黏膜中瘦素表达的影响,评价其对门脉高压性胃病的胃黏膜保护作用．方法:将患者随机分为正常对照组、正常干预组、空白对照组及试验组各15例,其中正常干预组及试验组给予口服瑞巴派特治疗．治疗前后内镜检查对比,用RT-PCR法分别检测治疗前后胃黏膜组织中瘦素mRNA的表达水平．结果:0 wk时,正常对照组瘦素mRNA表达量为0．344±0．202,空白对照组0．816±0．132,实验组0．803±0．143,与正常对照组相比,空白对照组与实验组的瘦素mRNA的表达有差异 (P<0．05);4 wk时,空白对照组瘦素mRNA表达量为0．867±0．170,试验组为1．120±0．237,正常干预组为0．397±0．199,与空白对照组相比, 试验组瘦素mRNA的表达增多;与正常干预组相比,试验组在治疗后其瘦素mRNA的表达显著升高(P<0．01)．内镜检查前后对比:药物治疗4 wk时试验组14例中胃黏膜的内镜表现不同程度改善12例(12/14),而空白对照组无一例改善．结论:瑞巴派特可通过增加胃黏膜中的瘦素表达,对门脉高压性胃病的胃黏膜起保护作用．     

瑞巴派特对提高胃溃疡愈合质量的实验研究

目的 比较瑞巴派特、奥美拉唑及两种药物联合应用干预大鼠胃溃疡愈合质量.方法 建立大鼠胃溃疡模型40只,均分为对照、瑞巴派特、奥美拉唑和瑞巴派特联合奥美拉唑组,7 d后观察大鼠胃溃疡大体形态,超声探察溃疡胃壁全层结构,局部组织学形态及检测黏膜白细胞介素(IL)-8,前列腺素(PG)E2和丙二醛(MDA)含量.结果 ①超声探查显示,对照组溃疡指数为(22.3±1.8)mm2,瑞巴派特组为(9.2±1.0)mm2,奥美拉唑组为(9.8±1.3)mm2,联合治疗组为(4.8±1.2)mm2.对照组均比用药组高(P值均＜0.05),瑞巴派特组和奥美拉唑组均比对照组降低(P值均＜0.05).②离体组织超声探查显示,对照组胃壁厚度明显增加、层次结构模糊消失,用药组胃壁厚度部分恢复正常、胃壁各层次结构部分重建.③组织学表现,用药组溃疡侵袭范围、炎性细胞浸润程度均明显轻于对照组,且周边黏膜再生程度明显优于对照组.④对照组胃黏膜IL-8为(1387.8±132.6)pg/ml,瑞巴派特组为(970.0±91.6)pg/ml,奥美拉唑组为(1102.2±76.9)pg/ml,联合治疗组为(934.4±110.2)pg/ml.对照组均比各用药组高(P值均＜0.05),瑞巴派特组与联合治疗组比奥美拉唑组明显降低(P值均＜0.05).⑤对照组胃黏膜MDA为(13.0±2.6)nmol/ml.瑞巴派特组为(8.5±4.8)nmol/ml,奥美拉唑组为(9.4±1.4)nmol/ml,联合治疗组为(4.6±1.4)nmol/ml.奥美拉唑组与瑞巴派特组均明显高于联合治疗组,且低于对照组(P值均＜0.05).⑥对照组胃黏膜PGE2为(55.0±22.5)pg/ml,瑞巴派特组为(103.5±12.5)pg/ml,奥美拉唑组为(96.9±7.0)pg/ml,联合治疗组为(235.5±26.0)pg/ml.奥美拉唑组与瑞巴派特组均明显高于对照组·且低于联合治疗组(P值均＜0.05).结论 与奥美拉唑相比,瑞巴派特同样能促进溃疡愈合进程,提高溃疡愈合质量;联合应用奥美拉唑,以不同机制同时作用于溃疡愈合过程,能更好地兼顾溃疡愈合的速度和质量.     

Activated protein C reduces ischemia/reperfusion-induced renal injury in rats by inhibiting leukocyte activation

We examined whether activated protein C (APC) reduces ischemia/reperfusion (I/R)-induced renal injury by inhibiting leukocyte activation. In a rat model, intravenous administration of APC markedly reduced I/R-induced renal dysfunction and histological changes, whereas intravenous administration of dansyl glutamylglycylarginyl chloromethyl ketone-treated factor Xa (DEGR-FXa; active-site-blocked factor Xa), heparin or diisopropyl fluorophosphate-treated APC (DIP-APC; inactive derivative of ARC) had no effect. Furthermore, APC significantly inhibited the I/R-induced decrease in renal tissue blood flow and the increase in the vascular permeability, whereas neither DEGR-FXa, heparin, nor DIP-APC produced such effects. Renal I/R-induced increases in plasma levels of fibrin degradation products were significantly inhibited by APC, DEGR-FXa, and heparin. These observations suggest that APC reduces I/R-induced renal injury independently of its anticoagulant effects but in a manner dependent on its serine protease activity. Renal levels of tumor necrosis factor-alpha (TNF-alpha), rat interleukin-8, and myeloperoxidase were significantly increased after renal I/R. These increases were significantly inhibited by APC but not by DEGR-FXa, heparin, or DIP-APC. Leukocytopenia produced effects similar to those of APC. These findings strongly suggest that APC protects against I/R-induced renal injury not by inhibiting coagulation abnormalities but by inhibiting activation of leukocytes that play an important role in I/R-induced renal injury. Inhibition of leukocyte activation by APC could be explained by the inhibitory activity of TNF-alpha. (Blood. 2000;95:3781-3787)     

Protection of gastric mucosa from ethanol induced injury by recombinant epidermal growth factor in rats

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Artemisia asiatica extracts protect against ethanol-induced injury in gastric mucosa of rats

Background and Aim:  Based on our previous studies that Artemisia asiatica extracts exert either antioxidative or cytoprotective actions against non-steroidal anti-inflammatory drugs or Helicobacter pylori -induced gastric mucosal injury, or imposes qualified ulcer healing in an acetic acid-induced gastric ulcer model, we investigated the protective effects of Artemisia asiatica extracts against ethanol-induced gastric mucosal injury.
Methods:  Sprague–Dawley rats received 4 g/kg body weight (BW) of absolute ethanol intragastrically, which produced visible hemorrhagic gastric lesions 60 min later.
Results:  In this animal setting, the pretreatment of Artemisia extracts (30 or 100 mg/kg BW), 1 h before ethanol administration, significantly attenuated the source of gastric injury, which was assessed with gross and microscopic analysis ( P  < 0.01). Protection from alcohol-induced damage with Artemisia pretreatment was associated with significantly decreased lipid peroxidation, protecting gastric mucosa from glutathione depletion, as well as the inhibition of the cytochrome 2E1 ethanol-metabolizing enzyme. It attenuated the expressions of ethanol-induced pro-inflammatory cytokines, including interleukin (IL)-1β and interferon-γ, a weak activation of IL-10, the inhibition of the alcohol-induced overexpression of intercellular adhesion molecule-1, and the considerable induction of heat shock protein-72 expression in gastric mucosal homogenates .
Conclusion:  The data suggest that the ethanol extracts of Artemisia asiatica exerted significant protection from alcohol-induced gastric mucosal injury through bioregulation, which is essential for cytoprotection and anti-inflammation.     

Inhibition of acid-induced lung injury by hyperosmolar sucrose in rats

RATIONALE: Acid aspiration causes acute lung injury (ALI). Recently, we showed that a brief intravascular infusion of hyperosmolar sucrose, given concurrently with airway acid instillation, effectively blocks the ensuing ALI. OBJECTIVES: The objective of the present study was to determine the extent to which intravascular infusion of hyperosmolar sucrose might protect against acid-induced ALI when given either before or after acid instillation. METHODS: Our studies were conducted in anesthetized rats and in isolated, blood-perfused rat lungs. We instilled HCl through the airway, and we quantified lung injury in terms of the extravascular lung water (EVLW) content, filtration coefficient (Kfc), and cell counts and protein concentration in the bronchoalveolar lavage. We infused hyperosmolar sucrose via the femoral vein. RESULTS: In anesthetized rats, airway HCl instillation induced ALI as indicated by a 52% increase of EVLW and a threefold increase in Kfc. However, a 15-min intravenous infusion of hyperosmolar sucrose given up to 1 h before or 30 min after acid instillation markedly blunted the increases in EVLW, as well as the increases in cell count, and in protein concentration in the bronchoalveolar lavage. Hyperosmolar pretreatment also blocked the acid-induced increase of Kfc. Studies in isolated perfused lungs indicated that the protective effect of hyperosmolar sucrose was leukocyte independent. CONCLUSIONS: We conclude that a brief period of vascular hyperosmolarity protects against acid-induced ALI when the infusion is administered shortly before, or shortly after, acid instillation in the airway. The potential applicability of hyperosmolar sucrose in therapy for ALI requires consideration.     

Alcohol injury to gastric mucosa in mice and its potentiation by stress

This investigation was initiated to separately evaluate the roles of dose and concentration of ethanol ingestion in the development of acute gastric mucosal injury and to determine the significance of stress as a potentiating factor in ethanol damage. A total of 423 mice were used in this study. Alcohol at the low concentration of 10% and at any of the doses used (1–5 g/kg wt) did not cause gastric mucosal lesions. Similarly, alcohol at the low dose of 1 g/kg wt at any of the concentrations used (10–50%) did not produce any gross injury to the stomach. A single oral administration of ethanol, given at doses of 2–5 g/kg wt and at concentrations of 25–50%, resulted in hyperemia and multiple fundic erosions and, less frequently, antral erosions. The incidence, number, and severity of these lesions rapidly increased with increase in ethanol concentration, ethanol dose, or both. Healing was rapid; at best, lesions were only barely visible 72 hours after alcohol ingestion. Repeated daily doses of ethanol given for 3–5 days did not increase the incidence and number of lesions, probably due to their capacity for rapid healing. Mild stress, in the form of 1-hour restraint in the cold room at 8°C, by itself caused very little mucosal injury in mice, but significantly potentiated the injurious effect of 35% ethanol administered in a 3 g/kg dose. Stress following alcohol intake potentiated gastric mucosal injury much more than if the stress preceded the alcohol ingestion. The incidence, number, and severity of erosions was here 3, 4 and 11 times, respectively, greater than the additive effect of alcohol and stress together (P<0.001). Thus, the extent of ethanol damage to the stomach related both to the concentration and dose of ethanol ingested. Stress, especially when following excessive ethanol intake, was a highly significant factor in the potentiation of acute alcoholic gastric mucosal injury.Supported by Grant-in-Aid AA-000312-1 from the Division on Alcoholism and Alcohol Abuse of the National Institute of Mental Health, Public Health Service.Dr. Kawashima was the recipient of a travel grant from the Natio Research Grant, Tokyo, Japan, for 1971.     

Protection of gastric mucosa in rats

We have studied the protective effects of truncal vagotomy, atropine, and PGE₂ against gastric mucosal injury produced by necrotizing agents (0.2 N NaOH, 0.6 N HCl, absolute ethanol), acetylsalicylic acid (ASA) and HCl, or serotonin (5HT). Vagotomy, atropine, and PGE₂ prevent the effects of different noxious agents. Vagotomy is protective only against 5HT and against ASA+0.15 N or 0.35 N HCl, whereas atropine and PGE₂ are also protective against the necrotizing agents. The effectiveness of vagotomy against ASA+0.35 N HCl does not depend on the inhibition of acid secretion and supports the hypothesis that removal of the vagal drive counteracts the effect of H⁺ back-diffusion.     

脂联素抑制炎症小体NLRP3表达减轻高糖高脂诱导内皮细胞损伤

目的 研究脂联素（APN）是否通过抑制炎症小体NLRP3表达减轻高糖高脂所致的内皮细胞损伤。方法 将培养的人脐静脉内皮细胞（human umbilical vein endothelial cells,HUVECs）分为6组:对照组、高糖高脂组、对照+ NLRP3 siRNA组,高糖高脂组+NLRP3 siRNA组,对照+APN组,高糖高脂+APN组。培养48 h后检测细胞存活率、凋亡率、炎症小体NLRP3表达水平。结果 与对照组相比,高糖高脂组细胞存活率显著下降,细胞凋亡显著升高,炎症小体NLRP3表达水平显著升高（均P<0.05）;炎症小体NLRP3 siRNA可有效的抑制炎症小体NLRP3的表达,改善高糖高脂引起的内皮细胞损伤（均P<0.05）;APN能抑制高糖高脂引起的炎症小体NLRP3表达增多,进而减轻高糖高脂引起的内皮损伤（均P<0.05）。结论 炎症小体NLRP3表达增多是高糖高脂诱导人脐静脉内皮细胞凋亡的内在机制,而脂联素可以通过抑制炎症小体NLRP3的过度表达发挥内皮保护作用。伤,降低心肌炎症反应。     

Rebamipide reduces indomethacin-induced gastric injury in mice via down-regulation of ICAM-1 expression

Non-steroidal anti-inflammatory drugs (NSAIDs) induced gastric mucosal injury occurs through subsequent events following free radical production derived from activated neutrophils. In this study, we hypothesized that rebamipide, a novel anti-ulcer agent, exerts a protective effect on NSAID-induced gastric injury through its antioxidant properties. The protective effect of rebamipide in a mouse model of indomethacin-induced gastric injury and mechanisms for this effect were investigated. Pre-treatment with rebamipide significantly inhibited indomethacin-induced gastric mucosal injury in mice. Gastric thiobarbituric acid reactive substances (TBARS) levels and myeloperoxidase (MPO) activity substantially increased 3 hr after indomethacin administration. These increases were significantly inhibited by pre-treatment with rebamipide. Furthermore, rebamipide pre-treatment notably decreased intercellular adhesion molecule-1 (ICAM-1) expression that was up-regulated in gastric tissue treated with indomethacin. Therefore, rebamipide may reduce indomethacin-induced gastric mucosal injuries through its antioxidant effect, which inhibits the neutrophil activation step following up-regulation of ICAM-1 expression on endothelial cells.     

Rebamipide, a novel antiulcer agent, attenuates Helicobacter pylori induced gastric mucosal cell injury associated with neutrophil derived oxidants.

The effect of rebamipide, a novel antiulcer compound, on Helicobacter pylori activated neutrophil dependent in vitro gastric epithelial cell injury was investigated. Luminol dependent chemiluminescence (ChL), which detects toxic oxidants from neutrophils exhibited a 12-fold increase when the bacterial suspension of H pylori was added to the isolated human neutrophils. This change was significantly attenuated by rebamipide at a concentration less than 1 mM, showing that rebamipide may inhibit oxidant production from H pylori elicited neutrophils. To assess whether rebamipide attenuates gastric mucosal injury, we tested its inhibitory action on H pylori induced gastric mucosal damage associated with neutrophils in vitro. Rabbit gastric mucosal cells were monolayered in culture wells and coincubated with human neutrophils and H pylori, and the cytotoxicity index was then calculated. Cultured gastric cells were significantly damaged when they were incubated with human neutrophils activated by H pylori. This cellular damage was attenuated by rebamipide in a dose-dependent manner. Furthermore, spectrophotometrical measurement showed that rebamipide (1 mM) inhibits urease activity by 21.7%. As monochloramine (an oxidant yielded by reaction of neutrophil derived chlorinated oxidant and ammonia) is proposed as an important toxic molecule in this model, the current findings suggest that the preventive effect of rebamipide on H pylori elicited neutrophil induced gastric mucosal injury may result from its inhibitory actions on the neutrophilic oxidative burst as well as H pylori derived urease activity.     

Betaine-palmitate reduces acetylsalicylic acid-induced gastric damage in rats

BACKGROUND: Acetylsalicylic acid (ASA)-induced gastric injury is reduced when ASA is administered along with phosphatidylcholine. The hydrolysis of endogenous phosphatidylcholine leads to the production of betaine, which may participate in the maintenance of cellular homeostasis. The present aims were to investigate the effects of exogenous betaine and its palmitic acid complex (betaine-palmitate) in the protection of the gastric mucosa in ASA-induced subacute damage. METHODS: Repeated doses of ASA were given intragastrically to male Wistar rats. Control rats were given vehicle only, while treated animals were challenged with ASA or with ASA along with betaine, palmitic acid or betaine-palmitate. The gastric mucosa was examined after 3 days and the nature of any microscopic mucosal injury was assessed by histology. The extent of macroscopic damage, changes in permeability (assessed by Evans blue method) and tissue ATP concentrations were determined in separate series. RESULTS: ASA induced a significant fall in the ATP content of the mucosa, which was not affected by the other drugs used in the study. However, the ASA-induced mucosal permeability increase could be completely reversed by betaine-palmitate supplementation. The extent of severity of the macroscopic and microscopic lesions was 33% and 2.45, respectively, for ASA, as compared with 15% and 2.2 for betaine, 14% and 1.9 for palmitic acid and 3% and 1.4 for betaine-palmitate. CONCLUSIONS: Betaine-palmitate affords a significant protective effect against ASA-induced injury, without influencing the ATP synthesis, and this suggests that the defence is due to its ability to prevent secondary damage.