Stress-induced Gastric Lesions Research Articles

Ranitidine use in pediatrics: current evidence-based review and recommendations

Ranitidine plays a pivotal role in routine pediatric practice. The multi-dimensional use and safety of ranitidine are not supported by any practical guidelines, which led to recommendations convened by a group of experts based on evidence and the clinical experience of experts. A group of general pediatricians and pediatric gastroenterologists from India were part of this panel. This group of experts reviewed the literature on topics that were unanimously agreed upon, for which no recommendations were available. The Delphi method was implemented to reach unified decisions, which led to the development of evidence-based recommendations. Gastritis and gastroesophageal reflux disease (GERD) are common conditions seen in pediatric practice. Ranitidine has a rapid onset of action compared to proton pump inhibitors (PPIs). It is a preferred drug for on-demand use for gastritis and managing stress-induced gastric lesions in critically ill pediatric patients. Ranitidine has an established role in the management of GERD, and it also prevents nocturnal acid reflux effectively. It helps in reducing gastric fluid volume when used as preoperative prophylaxis. Also, ranitidine has a better safety profile in comparison to PPIs. Recommendations on the use and safety of ranitidine in pediatrics were developed which will be a guiding tool for all practicing clinicians, highlighting the strength and benefits of ranitidine as a better and safe alternative to PPIs in short-term acid suppression for multiple indications.

The Role of Hydrogen Sulfide in Chronic Unpredictable Stress-Induced Gastric Lesions.

The aim of this study was to investigate the possible protective role of Hydrogen sulfide on chronic unpredictable stress (CUS) -induced gastric lesions. Materials and methods: 40 rats were divided into 4 groups: control group, stressed rats group, stressed + Aminooxyacetic acid (AOAA) (inhibitor of H2S synthesis; 50mg/kg/48hour; IP), stressed + Sodium hydrosulfide (NaHS) (donor of H2S, 5mg/kg/48hour; IP). In all the groups exposed to CUS, a set of chronic unpredictable stressors was applied for 6 weeks in random order. At the end of experimental protocol blood samples, gastric content and gastric tissues samples were collected. Gastric tissues histopathological changes were evaluated by macroscopic and microscopic examination. Gastric content pH, serum MDA level, whole blood GSH level were estimated. Expression of Caspase-3 (apoptotic marker) and BCL-xl (anti-apoptotic marker) was assessed by immunohistochemistry. Results: In all the groups exposed to CUS, there was a significant reduction in gastric pH value and a range of gastric lesions ranging from superficial to deep ulceration as evident by macroscopic and microscopic examination. Also, there was significant elevation in MDA serum level and significant reduction in anti-oxidant GSH blood level. In all stressed rats, the expression of Caspase-3 was significantly higher whereas a significant decrease in expression of anti-apoptotic protein BCL-xl was observed. These findings were aggravated by AOAA while using NaHS improved them. Conclusion: it seems that increasing bioavailability of H2S could have a protective role against CUS induced gastric lesions. The results suggest that this protection could be through anti-oxidant and anti-apoptotic effects.

Nervous mechanisms of restraint water-immersion stress-induced gastric mucosal lesion.

Stress-induced gastric mucosal lesion (SGML) is one of the most common visceral complications after trauma. Exploring the nervous mechanisms of SGML has become a research hotspot. Restraint water-immersion stress (RWIS) can induce GML and has been widely used to elucidate the nervous mechanisms of SGML. It is believed that RWIS-induced GML is mainly caused by the enhanced activity of vagal parasympathetic nerves. Many central nuclei, such as the dorsal motor nucleus of the vagus, nucleus of the solitary tract, supraoptic nucleus and paraventricular nucleus of the hypothalamus, mediodorsal nucleus of the thalamus, central nucleus of the amygdala and medial prefrontal cortex, are involved in the formation of SGML in varying degrees. Neurotransmitters/neuromodulators, such as nitric oxide, hydrogen sulfide, vasoactive intestinal peptide, calcitonin gene-related peptide, substance P, enkephalin, 5-hydroxytryptamine, acetylcholine, catecholamine, glutamate, γ-aminobutyric acid, oxytocin and arginine vasopressin, can participate in the regulation of stress. However, inconsistent and even contradictory results have been obtained regarding the actual roles of each nucleus in the nervous mechanism of RWIS-induced GML, such as the involvement of different nuclei with the time of RWIS, the different levels of involvement of the sub-regions of the same nucleus, and the diverse signalling molecules, remain to be further elucidated.

Inhibition of GKN2 Attenuates Acute Gastric Lesions Through the NLRP3 Inflammasome.

Objective: Acute gastric lesions are commonly seen in critically ill patients in the intensive care unit and can result in significant upper gastrointestinal bleeding. However, the signaling mechanisms that regulate this severe disease are still unclear. In this study, we explored the involvement of gastrokine 2 (GKN2) in the development of acute gastric lesions in mice. Approach: We measured the degree of injury using the water immersion restraint stress mouse model. Inflammatory cells and factors were analyzed after gastric lesion induction. The luciferase reporter assay was used to detect the transcription activity of nuclear receptor subfamily 3 group C member 1 (NR3C1) in regulation of GKN2. We also detected the downstream pathway of GKN2 in gastric lesions. Results: The results showed that GKN2 could aggravate stress-induced gastric lesions and gastric mucosal cell death. Moreover, the gastric lesion promoted by GKN2 was gastric acid independent. GKN2 could recruit neutrophils and promote the release of inflammatory factors to contribute to inflammation. NR3C1, activated by cortisol under stress, could act as a transcription factor to upregulate the expression of GKN2. Innovation: This study elucidates the process of gastric lesion at a molecular level and explores the possible contender biomarkers for diagnosis and drug targets in wound healing of gastric lesions. Conclusion: In conclusion, GKN2, which was upregulated by cortisol, aggravated the gastric lesion through activation of the inflammasome and inflammatory reaction.

The gastroprotective effect of the foxtail millet and adlay processing product against stress-induced gastric mucosal lesions in rats

Foxtail millet (Setaria italica (L.) P. Beauv.) and adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) seeds have substantial benefits possesses remarkable edible and nutritive values, and ease of processing and food manufacturing. They have nutraceutical properties in the form of antioxidants which prevent deterioration of human health and have long been used in traditional Chinese medicine as a remedy for many diseases. The present study is designed to investigate the gastroprotective effect of foxtail millet and adlay processing product (APP) diet on water immersion restraint stress (WIRS) induced ulceration in rats. We examined the effects of intake of AIN-93G diet containing either foxtail millet (10, 20 and 40%, 4 weeks) or APP (15 and 30%, 5 weeks) on macroscopic ulcer index (UI), plasma calcium level, lipid peroxidation products (estimated by the thiobarbituric acid reactive substances; TBARS), non-protein sulfhydryl (NPSH), digestive enzyme activities, and histopathology were determined. The results showed that pretreatment with millet and adlay diets significantly prevented the gastric mucosal lesion development. In addition, ulcerated rats showed depletion of NPSH levels whereas treatment with millet and adlay reverted this decline in stress-induced rats. Histological studies confirmed the results. The finding suggests that millet and adlay diets promote ulcer protection by the decrease in ulcer index, TBARS values and increase NPSH concentrations. Millet and adlay diets retain the advantage of being a natural product which may protect the gastric mucosa against ulceration.

QUERCETIN AND ELLAGIC ACID IN GASTRIC ULCER PREVENTION: AN INTEGRATED SCHEME OF THE POTENTIAL MECHANISMS OF ACTION FROM IN VIVO STUDY

Objective: The present study was initiated to describe the gastroprotective role of quercetin (Qu) and ellagic acid (EA) on aspirin-induced gastric ulcer (GU) in rats.Methods: Forty adult female albino rats of Wistar strain were distributed into: Control group, GU group, Omeprazole group, Qu group, and EA group. Gross examination, biochemical analyses including serum adrenocorticotropic hormone (ACTH), serotonin (ST), ferritin, heme oxygenase-1 (HO-1), interleukin-2 (IL-2), advanced glycosylation end products (AGEs), and fibronectin (FN) levels were estimated. Moreover, histopathological and histochemical examinations of stomach tissue samples were carried out.Results: Gross examination of gastric mucosa of rats in GU group revealed hyperemia of the stomach mucosa. Furthermore, rats in GU group experienced a significant rise in serum ACTH, ferritin, HO-1, IL-2 and AGEs levels accompanied with significant drop in serum ST and FN levels versus control counterparts. Pre-treatment of GU group with Omeprazole, Qu or EA caused marked improvement in the measured biochemical parameters. Histopathological and histochemical examinations of stomach tissue samples documented the protective action of Omeprazole, Qu and EA with different degrees against GU caused by aspirin.Conclusion: As a conclusion to this study, we can state that both Qu and EA have gastroprotective effect against aspirin-induced GU in rat model. Of note, Qu showed superior impact than EA as an antiulcer agent in this study. The corresponding mechanisms are speculated to be associated with inhibiting stress-induced gastric lesion, attenuating the oxidative stress, iron chelation and blunting ferritin level, modulating inflammatory cascade, and promoting the healing process.

QUERCETIN AND ELLAGIC ACID IN GASTRIC ULCER PREVENTION: AN INTEGRATED SCHEME OF THE POTENTIAL MECHANISMS OF ACTION FROM IN VIVO STUDY

Objective: The present study was initiated to describe the gastroprotective role of quercetin (Qu) and ellagic acid (EA) on aspirin-induced gastric ulcer (GU) in rats.Methods: Forty adult female albino rats of Wistar strain were distributed into: Control group, GU group, Omeprazole group, Qu group, and EA group. Gross examination, biochemical analyses including serum adrenocorticotropic hormone (ACTH), serotonin (ST), ferritin, heme oxygenase-1 (HO-1), interleukin-2 (IL-2), advanced glycosylation end products (AGEs), and fibronectin (FN) levels were estimated. Moreover, histopathological and histochemical examinations of stomach tissue samples were carried out.Results: Gross examination of gastric mucosa of rats in GU group revealed hyperemia of the stomach mucosa. Furthermore, rats in GU group experienced a significant rise in serum ACTH, ferritin, HO-1, IL-2 and AGEs levels accompanied with significant drop in serum ST and FN levels versus control counterparts. Pre-treatment of GU group with Omeprazole, Qu or EA caused marked improvement in the measured biochemical parameters. Histopathological and histochemical examinations of stomach tissue samples documented the protective action of Omeprazole, Qu and EA with different degrees against GU caused by aspirin.Conclusion: As a conclusion to this study, we can state that both Qu and EA have gastroprotective effect against aspirin-induced GU in rat model. Of note, Qu showed superior impact than EA as an antiulcer agent in this study. The corresponding mechanisms are speculated to be associated with inhibiting stress-induced gastric lesion, attenuating the oxidative stress, iron chelation and blunting ferritin level, modulating inflammatory cascade, and promoting the healing process.

Recent Advances in the Gastric Mucosal Protection Against Stress-induced Gastric Lesions. Importance of Renin-angiotensin Vasoactive Metabolites, Gaseous Mediators and Appetite Peptides.

Stress is known to cause severe adverse effects in the human gastrointestinal tract including mucosal microbleedings and erosions or even gastric ulceration but the mechanism of these complications has not been fully elucidated. The pathogenesis of stress-induced gastric damage involves the fall in Gastric Blood Flow (GBF), an increase in gastric acid secretion and gastric motility, enhanced adrenergic and cholinergic nerve activity and the rise in gastric mucosal generation of reactive oxygen species. The gastric mucosal defense mechanisms against the deleterious effect of stress include the activation of the hypothalamic-pituitary-adrenal axis which has been linked with glucocorticoids release capable of counteracting of stress-induced gastric lesions. Here we summarize the novel gastroprotective mechanisms against stress damage exhibited by angiotensin-(1-7), the newly discovered metabolite of Renin-Angiotensin System (RAS), the gaseous mediators such as nitric oxide (NO), hydrogen sulfide (H2S) or Carbon Monoxide (CO), and the food intake controlling peptides ghrelin, nesfatin- 1 and apelin possibly acting via brain-gut axis. These bioactive molecules such as RAS vasoactive metabolite angiotensin-(1-7) and appetite peptides have been shown to afford gastroprotective effect against stressinduced gastric lesions mainly mediated by an increase in gastric microcirculation. Gaseous mediators protect the gastric mucosa against stress lesions by mechanism involving the activation of PG/COX and CO/HO-1 biosynthetic pathways, and their anti-inflammatory and anti-oxidizing properties. Thus, these new components add new mechanistic aspects to the common cooperation of NO/NO-synthase, PG/COX systems and vasoactive sensory neuropeptides including CGRP but their gastroprotective efficacy against experimental stress ulcerogenesis requires the confirmation in human clinical trials.

Melatonin pretreatment improves gastric mucosal blood flow and maintains intestinal barrier function during hemorrhagic shock in dogs.

Melatonin improves hepatic perfusion after hemorrhagic shock and may reduce stress-induced gastric lesions. This study was designed to investigate whether pretreatment with melatonin may influence gastric mucosal microcirculatory perfusion (μflow), oxygenation (μHbO2 ), or intestinal barrier function during physiological and hemorrhagic conditions in dogs. In a randomized crossover study, five anesthetized foxhounds received melatonin 100μgkg-1 or vehicle (ethanol 5%) intravenously in the absence or presence of hemorrhagic shock (60minutes, -20% blood volume). Systemic hemodynamic variables, gastric mucosal perfusion, and oxygenation were recorded continuously; intestinal barrier function was assessed intermittently via xylose absorption. During hemorrhagic shock, melatonin significantly attenuated the decrease in μflow, compared with vehicle (-19±9 vs -43±10aU, P<.05), without influence on μHbO2 . A significant increase in xylose absorption was detected during hemorrhage in vehicle-treated dogs, compared with sham-operated animals (13±2 vs 8±1 relative amounts, P<.05); this was absent in melatonin-treated animals (6±1 relative amounts). Melatonin did not influence macrocirculation. Melatonin improves regional blood flow suggesting improved oxygen delivery in gastric mucosa during hemorrhagic shock. This could provide a mechanism for the observed protection of intestinal barrier function in dogs.

In vivo effect of Piper sarmentosum methanolic extract on stress-induced gastric ulcers in rats.

IntroductionPiper sarmentosum (Piperaceae) is traditionally used by Asians to treat numerous common ailments including asthma, fever and gastritis. The aim of the research was to determine and compare the effects of Piper sarmentosum (PS) with omeprazole (OMZ) on gastric parameters in rats exposed to restraint stress.Material and methodsThe methanolic extract of PS was prepared in the dose of 500 mg/kg. Twenty-eight male Wistar rats were assigned to 4 equal sized groups: two control groups and two treated groups which were supplemented with either PS or OMZ orally at a dose of 500 mg/kg and 20 mg/kg body weight respectively. After 28 days of treatment, one control group, the PS and OMZ group were subjected to a single exposure of water-immersion restraint stress for 3.5 h. After the last exposure to stress, the stomach was excised for evaluation of the parameters.ResultsOral supplementation of PS was as effective in preventing the formation of gastric lesion when compared with OMZ (p < 0.05). The increased gastric acidity and MDA due to stress was also reduced with supplementation of PS and OMZ. Only PS had the ability to reduce prostaglandin E2 loss (p = 0.0067) and have the ability to down regulate cyclooxygenase-2 (COX-2) mRNA expression (p = 0.01) with stress exposure.ConclusionsPiper sarmentosum possesses a similar protective effect against stress-induced gastric lesions as omeprazole. The protective effect was associated with decreased lipid peroxidation, increased prostaglandin E2, reduction in gastric acidity and reduction in COX-2 mRNA expression which was altered by stress.

Mo1257 Crosstalk Between Carbon Monoxide (CO) Released From Tricarbonyldichlororuthenium (II) Dimer (Corm-2) and Endogenous Nitric Oxide (NO) in Gastroprotection Against Stress-Induced Gastric Lesions

Mo1257 Crosstalk Between Carbon Monoxide (CO) Released From Tricarbonyldichlororuthenium (II) Dimer (Corm-2) and Endogenous Nitric Oxide (NO) in Gastroprotection Against Stress-Induced Gastric Lesions

The Protective Role of Carbon Monoxide (CO) Produced by Heme Oxygenases and Derived from the CO-Releasing Molecule CORM-2 in the Pathogenesis of Stress-Induced Gastric Lesions: Evidence for Non-Involvement of Nitric Oxide (NO).

Carbon monoxide (CO) produced by heme oxygenase (HO)-1 and HO-2 or released from the CO-donor, tricarbonyldichlororuthenium (II) dimer (CORM-2) causes vasodilation, with unknown efficacy against stress-induced gastric lesions. We studied whether pretreatment with CORM-2 (0.1–10 mg/kg oral gavage (i.g.)), RuCl3 (1 mg/kg i.g.), zinc protoporphyrin IX (ZnPP) (10 mg/kg intraperitoneally (i.p.)), hemin (1–10 mg/kg i.g.) and CORM-2 (1 mg/kg i.g.) combined with NG-nitro-l-arginine (l-NNA, 20 mg/kg i.p.), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 mg/kg i.p.), indomethacin (5 mg/kg i.p.), SC-560 (5 mg/kg i.g.), and celecoxib (10 mg/kg i.g.) affects gastric lesions following 3.5 h of water immersion and restraint stress (WRS). Gastric blood flow (GBF), the number of gastric lesions and gastric CO and nitric oxide (NO) contents, blood carboxyhemoglobin (COHb) level and the gastric expression of HO-1, HO-2, hypoxia inducible factor 1α (HIF-1α), tumor necrosis factor α (TNF-α), cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) were determined. CORM-2 (1 mg/kg i.g.) and hemin (10 mg/kg i.g.) significantly decreased WRS lesions while increasing GBF, however, RuCl3 was ineffective. The impact of CORM-2 was reversed by ZnPP, ODQ, indomethacin, SC-560 and celecoxib, but not by l-NNA. CORM-2 decreased NO and increased HO-1 expression and CO and COHb content, downregulated HIF-1α, as well as WRS-elevated COX-2 and iNOS mRNAs. Gastroprotection by CORM-2 and HO depends upon CO’s hyperemic and anti-inflammatory properties, but is independent of NO.

Remedial Effects of Resveratrol on Chronic Unpredictable Stress-Induced Gastric Lesions in Male Albino Rats

Objectives: Stress of various patterns has been linked to pathologies of body organs, including gastric mucosal damage. The polyphenol Resveratrol (RES) has been reported to have anti-ulcer properties against some models of gastric ulcer. However, its effect against experimental chronic unpredictable stress (CUS)-induced ulcer per se was not studied before. This study aims to investigate the gastric mucosal damage induced by CUS, its potential prevention by RES, and the mechanisms of action implicated. Methods. Thirty two rats were randomized into 4 groups, 8 rats each: Control, Control+ RES, CUS, and CUS+RES. The CUS was applied for 3 weeks, during which the vehicle (Normal Saline) or RES (25 mg.kg-1) was intraperitoneally administered on daily doses. Ulceration index, oxidative, inflammatory and apoptotic parameters were measured. Results. CUS induced severe gastric lesions of various extents, with considerable erosive microscopic features. There was significant increase in the levels of TBARS, TNF-α, IL-6, Bax and caspase-3 with concomitant significant decrease in the levels of SOD, GPX, PGE2, and Bcl-2 in CUS rats compared to control rats. Resveratrol treatment to CUS stressed rats brought all of these parameters to control levels, and remarkably maintained the normal morphology and microscopic architectures of gastric tissue. Conclusion. The present data show that supplementation with resveratrol ameliorates CUS-induced gastric lesions via its antioxidant, anti-inflammatory and anti-apoptotic potentials; a promising protective consequence that may demand further exploration.

EXPRESSION OF REG1Α, GAST AND TGFB1 GENES IN CONDITIONS OF STRESSINDUCED GASTRIC MUCOUS LESIONS DEVELOPMENT AND HEALING IN RATS.

Analysis of Reg1a gene expression in rat gastric mucosa under development and healing of stress-induced lesions was carried out. Increased expression of Reg1a was observed after 1 hour of stressor impact - 2,1 times, and achieved the maximum level expression after 3 hours of stress exposure - 3,5 times, that occurred on the background of lipid peroxidation intensification and antioxidant system dysfunction. The sharp decrease in 1,6 and 2 times of Reg1a gene expression was shown in 12 and 24 hours respectively after termination of the stressor action. Analysis of Gast gene expression did not confirm that gastrin stimulated Reg1a expression in gastric mucosa under water immersion restraint stress. The positive correlation between Reg1a and Tgfb1 genes expression was determined in the dynamics of stress-induced gastric lesions’ development and healing, which may indicate the involvement of Tgfb1 to acceleration of lesion’s healing.

Preventive Effects of Tocotrienol on Stress-Induced Gastric Mucosal Lesions and Its Relation to Oxidative and Inflammatory Biomarkers.

This study aimed to investigate the possible gastroprotective effect of tocotrienol against water-immersion restraint stress (WIRS) induced gastric ulcers in rats by measuring its effect on gastric mucosal nitric oxide (NO), oxidative stress, and inflammatory biomarkers. Twenty-eight male Wistar rats were randomly assigned to four groups of seven rats. The two control groups were administered vitamin-free palm oil (vehicle) and the two treatment groups were given omeprazole (20 mg/kg) or tocotrienol (60 mg/kg) orally. After 28 days, rats from one control group and both treated groups were subjected to WIRS for 3.5 hours once. Malondialdehyde (MDA), NO content, and superoxide dismutase (SOD) activity were assayed in gastric tissue homogenates. Gastric tissue SOD, iNOS, TNF-α and IL1-β expression were measured. WIRS increased the gastric MDA, NO, and pro-inflammatory cytokines levels significantly when compared to the non-stressed control group. Administration of tocotrienol and omeprazole displayed significant protection against gastric ulcers induced by exposure to WIRS by correction of both ulcer score and MDA content. Tissue content of TNF-α and SOD activity were markedly reduced by the treatment with tocotrienol but not omeprazole. Tocotrienol significantly corrected nitrite to near normal levels and attenuated iNOS gene expression, which was upregulated in this ulcer model. In conclusion, oral supplementation with tocotrienol provides a gastroprotective effect in WIRS-induced ulcers. Gastroprotection is mediated through 1) free radical scavenging activity, 2) the increase in gastric mucosal antioxidant enzyme activity, 3) normalisation of gastric mucosal NO through reduction of iNOS expression, and 4) attenuation of inflammatory cytokines. In comparison to omeprazole, it exerts similar effectiveness but has a more diverse mechanism of protection, particularly through its effect on NO, SOD activity, and TNF-α.

Endogenous prostaglandins and afferent sensory nerves in gastroprotective effect of hydrogen sulfide against stress-induced gastric lesions.

Hydrogen sulfide (H2S) plays an important role in human physiology, exerting vasodilatory, neuromodulatory and anti-inflammatory effects. H2S has been implicated in the mechanism of gastrointestinal integrity but whether this gaseous mediator can affect hemorrhagic lesions induced by stress has been little elucidated. We studied the effect of the H2S precursor L-cysteine, H2S-donor NaHS, the H2S synthesizing enzyme (CSE) activity inhibitor- D,L-propargylglycine (PAG) and the gastric H2S production by CSE/CBS/3-MST activity in water immersion and restraint stress (WRS) ulcerogenesis and the accompanying changes in gastric blood flow (GBF). The role of endogenous prostaglandins (PGs) and sensory afferent nerves releasing calcitonin gene-related peptide (CGRP) in the mechanism of gastroprotection induced by H2S was examined in capsaicin-denervated rats and those pretreated with capsazepine to inhibit activity of vanilloid receptors (VR-1). Rats were pretreated with vehicle, NaHS, the donor of H2S and or L-cysteine, the H2S precursor, with or without the concurrent treatment with 1) nonselective (indomethacin) and selective cyclooxygenase (COX)-1 (SC-560) or COX-2 (rofecoxib) inhibitors. The expression of mRNA and protein for COX-1 and COX-2 were analyzed in gastric mucosa pretreated with NaHS with or without PAG. Both NaHS and L-cysteine dose-dependently attenuated severity of WRS-induced gastric lesions and significantly increased GBF. These effects were significantly reduced by pretreatment with PAG and capsaicin denervation. NaHS increased gastric H2S production via CSE/CBS but not 3-MST activity. Inhibition of COX-1 and COX-2 activity significantly diminished NaHS- and L-cysteine-induced protection and hyperemia. NaHS increased expression of COX-1, COX-2 mRNAs and proteins and raised CGRP mRNA expression. These effects of NaHS on COX-1 and COX-2 protein contents were reversed by PAG and capsaicin denervation. We conclude that H2S exerts gastroprotection against WRS-induced gastric lesions by the mechanism involving enhancement in gastric microcirculation mediated by endogenous PGs, sensory afferent nerves releasing CGRP and the activation of VR-1 receptors.

Intravenous Ilaprazole Is More Potent than Oral Ilaprazole Against Gastric Lesions in Rats

Ilaprazole is a novel proton pump inhibitor that has been marketed as an oral therapy for acid-related diseases in China and Korea. This study aimed to compare the gastroprotective effects of intravenous and enteral ilaprazole in rat models. The rats were divided into 7-8 groups receiving vehicle, esomeprazole, and different doses of intravenous and enteral ilaprazole. The rats were then exposed to indomethacin (30mg/kg, i.g.), or water-immersion stress and gastric lesions were examined. The effects of different treatments on histamine (10μmol/kg/h)-induced acid secretion were also observed. Intravenous ilaprazole exhibited high antiulcer activity in a dose-dependent manner. Ilaprazole at a dose of 3mg/kg decreased ulcer number and index to the same extent as 20mg/kg esomeprazole. Moreover, the potency of intravenous ilaprazole is superior to that of intragastric ilaprazole. In anesthetized rats, the inhibitory effect of intravenous ilaprazole on histamine-induced acid secretion is faster and longer-lasting than that of intraduodenal ilaprazole. Intravenous ilaprazole is more potent than oral ilaprazole against indomethacin- or stress-induced gastric lesions, with faster and longer inhibition of acid secretion.

MELATONIN PROTECTS THE INTEGRITY OF GASTRIC STRUCTURE FROM A STERILE TISSUE INJURY AND AUGMENTS BOTH MONONUCLEAR AND POLYMORPHONUCLEAR PERIPHERAL BLOOD CELLS INDUCED BY THE INJURY IN WISTAR ALBINO RATS

Peptic ulcer is a common upper gastrointestinal dis ease that remains a major public health problem. Ga stric ulceration caused by Nonsteroidal Anti-Inflammatory Drugs (NSAID), stress and alcohol are the common causes of ga stric ulcer formation in humans following helicobacter pylori b acterial infection of the stomach. The neurohormone , melatonin was reported to protect against NSAID- and stress-i nduced gastric lesions. We sought to determine whet her melatonin, which is known to have antioxidant effects and indu ces systemic leukocyte mobilization, can protect th e gastric structure from a sterile tissue injury. Equally div ided melatonin or vehicle pre-treated Albino rats (N = 20) were subjected to sterile tissue injury of gastric ulcer ation using hypertonic sodium chloride solution. Me latonin treatment significantly protected the animals from gastric le sions induced by hypertonic salt compared to contro l vehicle-treated animals that show formation of gastric lesions in a ll examined rats. In addition, melatonin treatment significantly increased sterile tissue injury induction of both m ononuclear and polymorphonuclear peripheral blood cells. We conclude that melatonin protects sterile tissue inj ury-induced gastric lesions and augments white bloo d cell populations in response to this type of tissue injury.

Protective Effect of Repeatedly Preadministered Brazilian Propolis Ethanol Extract against Stress‐Induced Gastric Mucosal Lesions in Rats

The present study was conducted to clarify the protective effect of Brazilian propolis ethanol extract (BPEE) against stress-induced gastric mucosal lesions in rats. The protective effect of BPEE against gastric mucosal lesions in male Wistar rats exposed to water-immersion restraint stress (WIRS) for 6 h was compared between its repeated preadministration (50 mg/kg/day, 7 days) and its single preadministration (50 mg/kg). The repeated BPEE preadministration attenuated WIRS-induced gastric mucosal lesions and gastric mucosal oxidative stress more largely than the single BPEE preadministration. In addition, the repeated BPEE preadministration attenuated neutrophil infiltration in the gastric mucosa of rats exposed to WIRS. The protective effect of the repeated preadministration of BPEE against WIRS-induced gastric mucosal lesions was similar to that of a single preadministration of vitamin E (250 mg/kg) in terms of the extent and manner of protection. From these findings, it is concluded that BPEE preadministered in a repeated manner protects against gastric mucosal lesions in rats exposed to WIRS more effectively than BPEE preadministered in a single manner possibly through its antioxidant and anti-inflammatory actions.

Angiotensin (1–7) protects against stress-induced gastric lesions in rats

Stress ulcers can develop with severe physiological stress, and have been proposed as being brain-driven events. New findings continue to suggest that stress ulcers can be more effectively managed through central manipulation rather than by simply altering local gastric factors. Angiotensin (1–7) (Ang (1–7)) is present as an endogenous constituent of the brain and stomach. The beneficial effects of Ang (1–7) have been confirmed in the vessels, brain, heart, kidney, liver and lungs, but not in the stomach. Given the accumulating evidence suggesting the anti-stress activities of Ang (1–7), its potential gastroprotective effect in the context of stress requires further investigation. In the present study, rat gastric mucosal lesions were induced by 2h of cold-restraint stress. We observed that these lesions were significantly attenuated after 1 week of intracerebroventricular treatment with Ang (1–7). This gastroprotective effect was associated with attenuated oxidative stress and suppressed acid secretion. Brain Ang (1–7) administration profoundly modified responses to stress, indicated by altered levels of several stress hormones, including Ang II, glucocorticoid, norepinephrine, serotonin, and dopamine, in blood or stress-related brain regions. These findings indicate that Ang (1–7) exerts anti-stress activities by restoring the gastric microenvironment and modulating the stress pathways. Ang (1–7) may be a promising agent for stress ulcer prophylaxis and therapy, administered through brain-permeable mimics or carriers.