Gastric Mucosal Blood Flow Research Articles

Allyl isothiocyanate, an activator of TRPA1, increases gastric mucosal blood flow through calcitonin gene-related peptide and adrenomedullin in anesthetized rats

Allyl isothiocyanate (AITC) activates transient receptor potential ankyrin 1 (TRPA1) channel, which is involved in the control of intestinal mucosal blood flow. However, the mechanism underlying the increased gastric mucosal blood flow (GMBF) in response to AITC remains unknown. We examined the effect of AITC on GMBF in the ex vivo stomachs of normal and sensory deafferented rats using a laser Doppler flowmeter. Mucosal application of AITC increased GMBF in a concentration-dependent manner. Repeated AITC exposure resulted in a marked desensitization. The increased GMBF response induced by AITC was entirely blocked by co-application of TRPA1 channel blockers HC-030031 or AP-18. Increased GMBF in response to AITC was significantly attenuated by chemical deafferentation following systemic capsaicin injections (total dose: 100 mg/kg). In contrast, increased GMBF responses to capsaicin, a transient receptor potential vanilloid 1 (TRPV1) activator, were completely abolished by chemical deafferentation. The increased GMBF response to AITC was markedly inhibited by BIBN 4096, a calcitonin gene-related peptide receptor (CGRP) antagonist, or AGP-8412, an adrenomedullin receptor antagonist. These results suggest that AITC-stimulated TRPA1 activation results in the increased GMBF through the release of CGRP and adrenomedullin.

Glucagon-like peptide-2 protects the gastric mucosa via regulating blood flow and metabolites.

Refractory peptic ulcers lead to perforation and hemorrhage, which are fatal. However, these remain a therapeutic challenge. Gastric mucosal blood flow is crucial in maintaining gastric mucosal health. It's reported that Glucagon-like peptide-2 (GLP-2), a gastrointestinal hormone, stimulated intestinal blood flow. However, the direct role of GLP-2 in gastric mucosal blood flow and metabolites remain unclear. Here, we speculated that GLP-2 might protect the gastric mucosa by increasing gastric mucosal blood flow and regulating metabolites. This study was conducted to evaluate the role of GLP-2 in gastric mucosal lesions and its underlying mechanism. We analyzed endogenous GLP-2 during gastric mucosal injury in the serum. Rats were randomly divided into two groups, with 36 rats in each group as follows: (1) normal control group (NC1); (2) ethanol model group (EC1); rats in EC1 and NC1 groups were intragastrically administered ethanol (1 ml/200 g body weight) and distilled water (1 ml/200 g body weight). The serum was collected 10 min before intragastric administration and 15, 30, 60, 90, and 120 min after intragastric administration. Furthermore, additional male Sprague-Dawley rats were randomly divided into three groups, with six rats in each group as follows: (1) normal control group (NC); (2) ethanol model group (EC); (3) 10 μg/200 g body weight GLP-2 group (GLP-2). Rats in the NC and EC groups were intraperitoneally injected with saline. Those in the GLP-2 group were intraperitoneally injected with GLP-2. Thirty minutes later, rats in the EC and GLP-2 groups were intragastrically administered ethanol (1 ml/200 g body weight), and rats in the NC group were intragastrically administered distilled water (1 ml/200 g body weight). After the intragastric administration of ethanol for 1 h, the animals were anesthetized and gastric mucosal blood flow was measured. Serum were collected for ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) metabolomics. There were no significant change in endogenous GLP-2 during gastric mucosal injury (P<0.05). Pretreatment with GLP-2 significantly reduced ethanol-induced gastric mucosal lesions by improving the gastric mucosal blood flow, as examined using a laser Doppler flow meter, Guth Scale, hematoxylin-eosin staining, and two-photon microscopy. UPLC-MS/MS analyses showed that GLP-2 also maintained a steady state of linoleic acid metabolism. Taken together, GLP-2 protects the gastric mucosa against ethanol-induced lesions by improving gastric mucosa blood flow and affecting linoleic acid metabolism.

Daikenchuto, a Traditional Kampo Medicine, Facilitates Mucosal Hyperemic Responses through Activation of TRPA1- and TRPV1-Expressing Sensory Nerves in Rat Stomach

AbstractDaikenchuto is a traditional Kampo medicine used to treat cold sensations and dysmotility in the abdomen. This study investigated the roles of transient receptor potential ankyrin 1- and transient reporter potential vanilloid 1-expressing sensory nerves in daikenchuto-induced gastric mucosal blood flow by pharmacological and immunohistochemical analyses using male Sprague-Dawley rats. Gastric mucosal blood flow was measured in ex vivo stomachs using a laser Doppler flowmeter. Transient receptor potential ankyrin 1 activator allyl isothiocyanate or transient reporter potential vanilloid 1 activator capsaicin were applied for 10 min, and daikenchuto was applied for 10 or 30 min to the rat stomach. Transient reporter potential vanilloid 1 blocker N-(4-t-butylphenyl)-4-(3-chlopyridin-2-yl) tetrahydropyrazine-1(2H)-carboxamide and transient receptor potential ankyrin 1 blocker A-967079 were also administered intragastrically. Capsaicin and allyl isothiocyanate increased gastric mucosal blood flow immediately after the intragastric application, which was almost completely inhibited by N-(4-t-butylphenyl)-4-(3-chlopyridin-2-yl) tetrahydropyrazine-1(2H)-carboxamide and A-967079, respectively. Daikenchuto increased gastric mucosal blood flow in a concentration-dependent manner. A-967079 significantly inhibited the increase in gastric mucosal blood flow induced by daikenchuto. In contrast, N-(4-t-butylphenyl)-4-(3-chlopyridin-2-yl) tetrahydropyrazine-1(2H)-carboxamide inhibited the responses to daikenchuto only in the late phase but not in the initial phase. Interestingly, in the deafferentation of capsaicin-sensitive sensory fiber in rats, the increased gastric mucosal blood flow induced by daikenchuto was only decreased in the late phase. Although transient receptor potential ankyrin 1- and transient reporter potential vanilloid 1-immunoreactive fibers were observed around the submucosal blood vessels of normal subjects, they were completely absent in the deafferentation of capsaicin-sensitive sensory fibers. Thus, daikenchuto increases gastric mucosal blood flow via transient receptor potential ankyrin 1- and transient reporter potential vanilloid 1-co-expressing sensory nerves in rat stomachs.

Gastric mucosal function in portal hypertensive gastropathy secondary to schistosomal hepatic fibrosis: effect of sclerotherapy

Gastric mucosal function in portal hypertensive gastropathy secondary to schistosomal hepatic fibrosis [SHF] was evaluated. Group I comprised 20 patients with no bleeding;10 had portal hypertensive gastropathy [PHG]. Group II comprised 20 patients with bleeding. Free acidity, total acidity, basal acid output, serum pepsinogen I, gastric mucosal blood flow [GMBF] and gastrin were significantly lower in group II, whereas serum gastrin and somatostatin staining were significantly higher. No histopathological changes were noted between both groups, In conclusion, bleeding caused by SHF results in hypoacidity, hypergastrinaemia and hypopepsinogenaemia. Estimated GMBF distinguishes patients with PHG and those who are bleeders

The Protective Effect of Dapsone Against Ethanol, Stress, and Indomethacin-Induced Gastric Erosion in Rats

Several factors contribute to the development of gastric erosions, including corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, and stress. These factors can cause or worsen gastrointestinal ulcers by activating inflammatory pathways or by altering gastric mucosal blood flow. Dapsone is an antimicrobial compound with anti-inflammatory properties. The aim of this study was to evaluate the protective effects of dapsone against gastric erosions induced by alcohol, stress, or indomethacin. Gastric damage was induced in male rats in three different experimental models: ethanol (5 ml/kg, p.o.)-, water-immersion stress-, and indomethacin (30 mg/kg, p.o.)- induced ulcer. Rats in each of these three experimental models were divided into five groups: Normal group, 2. Control group (gastric damage+vehicle), 3. Gastric damage+dapsone 1 mg/kg, 4. Gastric damage+dapsone 3 mg/kg, 5. Gastric damage+dapsone 10 mg/kg. In this study, the J- score ulcer index and histopathological assessment were performed. In addition, inflammatory cytokines levels, NF-κB expression, and MPO activity were determined. Dapsone reduced the tissue injuries and erosion area in all three experimental groups compared to the control group. In addition, serum levels of inflammatory cytokines, TNF-alpha, and IL-1β were reduced in the dapsone treatment groups. The expression of NF-κB and tissue concentration of myeloperoxidase (a marker of neutrophil activation) was also reduced in rats given dapsone. To conclude, dapsone exhibits significant protective effects against the development of experimental gastric erosions in rats, and these effects seem to be related to its anti-inflammatory and antioxidant properties.

A Study of Antiulcer Activity in Cynodon dactylon Leaves Extract on Albino Rats

Peptic ulcer is a chronic, non-malignant inflammatory disease characterized by ulceration in the upper gastro-intestinal tract (stomach and duodenum) where parietal cells are found. The aetiology of gastric ulceration is multifactorial and not clearly defined, but some predisposing factors have been implicated. This includes duration of starvation, nature of food ingested, bile reflux, lessened mucosal resistance, alteration of gastric mucosal blood flow, disruption of gastric mucosal barrier by stress, decrease in alkaline mucosal bicarbonate and mucus secretion, over dosage and or prolonged administration of non-steroidal anti-inflammatory drugs. Among numerous species of plants growing in India, Durva or taxonomically the Cynodon dactylon occupies a key position in ethno medicinal practices and traditional medical knowledge systems (Ayurveda, Unani, Nepalese, and Chinese). Durva consists of dried whole plant of Cynodon dactylon (Linn.) Pers. (Family: Poaceae), an elegant, tenacious, perennial, creeping grass growing throughout the country. In our present study, the mature green leaves of Cynodon dactylon belongs to family Poaceae were collected from in and around area of Thanjavur District, Tamil Nadu, South India. The plant was identified with the help of Manual of Tamil Nadu and Karnatic flora with standard references. From this study, it is clear that C. dactylon leaf extract has significant anti-ulcer activity in animal models. The extract is non-toxic even at relatively high concentrations. The anti-ulcer activity is probably due to the presence of flavonoids.

Chronic atrophic gastritis and intestinal metaplasia induced by high-salt and N-methyl-N'-nitro-N-nitrosoguanidine intake in rats.

The aim of the present study was to induce chronic atrophic gastritis (CAG) with intestinal metaplasia (IM) in rats by administering saturated salt and methyl-N'-nitro-N-nitrosoguanidine (MNNG) via oral gavage. Changes in gastric mucosal blood microcirculation and activation of the cyclo-oxygenase-2 (COX-2)/hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway during CAG and IM development were investigated. After administering saturated salt and MNNG for 25 weeks, mild atrophy was detected in the stomach of model rats using hematoxylin and eosin staining. CAG with IM was successfully induced in the gastric mucosa of the model rats after 35 weeks. Gastric mucosal blood flow was decreased in comparison with controls as early as 15 weeks after treatment to induce CAG and the mRNA expression levels of COX-2, HIF-1α, vascular endothelial growth factor receptor (VEGFR)1 and VEGFR2 were increased in comparison with untreated rats as early as 25 weeks after treatment. HIF-1α, COX-2 and VEGFR2 expression levels were increased as early as 25 weeks after CAG induction treatment when compared to controls and HIF-1α, COX-2, VEGFR1 and VEGFR2 expression levels were significantly increased after 35 weeks. These findings indicated that administering saturated salt and MNNG by gavage for 35 weeks successfully induced CAG and IM in rats. Furthermore, the microcirculation was disturbed before activation of the COX-2/HIF-1α/VEGF signaling pathway.

Relationship between Gastric Blood Perfusion and Gastric Mucosal Injury Induced by Acute Cerebrovascular Disease in Rats

This study aims to discuss the relationship between gastric perfusion and gastric mucosal injury induced by acute cerebrovascular disease in rats. Healthy adult male Wistar rats weighing 280-320 g are randomly divided into the following 4 groups: middle cerebral artery occlusion-reperfusion group, middle cerebral artery occlusion -sham group, gastric ischemia-reperfusion group and gastric ischemia-sham group, with 12 in each group. In gastric ischemia-reperfusion group, the similar changes occur to the mucous membrane of the rats, such as hyperaemia, edema, spotty or patchy hemorrhage and partial mucous exfoliation. There is no significant difference between middle cerebral artery occlusion-reperfusion group and gastric ischemia-reperfusion group in the number of gastrin cells and the expression of gas, but the number of gastrin cells and the expression of gas are significantly higher than those of their corresponding sham operation group, resulting in statistically significant difference. The gastric mucosal blood flow is significantly increased in the middle and high dose groups, which has significant difference compared with normal saline group (p<0.05). One of the important mechanisms of Calcitonin gene-related peptide protecting ischemic gastric mucosal injury is to increase gastric mucosal blood perfusion and improve microcirculation.

Gastroprotective effect of the root extract of Alpinia officinarum Hance (Zingiberoside) against acute indomethacin-induced gastric injuries in rats: Involvement of H+/K+-ATPase and prostaglandin E receptors

Purpose: To investigate the protective effects of Alpinia officinarum root ethanol extract (AOE) and galangin against acute indomethacin-induced injury on rat gastric mucosaMethods: Sprague-Dawley rats were daily treated with bismuth potassium citrate (0.08 g/kg), AOE at doses of 0.09, 0.18 and 0.36 g/kg; and galangin (0.2 g/kg) for 15 days. Then, gastric injury on rats was induced by intragastric administration of indomethacin (30 mg/kg). Blood flow and thickness of gastric mucosa were determined using neutral red clearance test and Alcian blue staining. The activity of H+/K+-ATPase was assayed using a biochemical kit. Prostaglandin E receptor expressions were assayed by western blotting.Results: High doses of ethanol extract of Alpinia officinarum root significantly inhibited H+/K+-ATPase activity by 8.12 % (p &lt; 0.01), increased gastric mucosal blood flow (p &lt; 0.001), enhanced mucus thickness (p &lt; 0.05), and elevated the activities of prostaglandin E receptors 1 and 4 (p &lt; 0.05).Galangin significantly inhibited H+/K+-ATPase activity by 4.82 % (p &lt; 0.05) and increased gastric mucosal blood flow (p &lt; 0.01).Conclusion: The ethanol extract of Alpinia officinarum root attenuates indomethacin-induced gastric injury by reinforcing gastric mucosal barrier and inhibiting excessive gastric acid secretion. Thus, the extract can be potentially developed for management of gastric injuries.&#x0D; Keywords: Galangin, Gastric mucosal barrier, Gastric acid, Prostaglandin, Indomethacin

Protective Effects of Wheat Peptides against Ethanol-Induced Gastric Mucosal Lesions in Rats: Vasodilation and Anti-Inflammation.

Alcohol consumption increases the risk of gastritis and gastric ulcer. Nutritional alternatives are considered for relieving the progression of gastric mucosal lesions instead of conventional drugs that produce side effects. This study was designed to evaluate the gastroprotective effects and investigate the defensive mechanisms of wheat peptides against ethanol-induced acute gastric mucosal injury in rats. Sixty male Sprague–Dawley rats were divided into six groups and orally treated with wheat peptides (0.1, 0.2, 0.4 g/kgbw) and omeprazole (20 mg/kgbw) for 4 weeks, following absolute ethanol administration for 1 h. Pretreatment with wheat peptides obviously enhanced the vasodilation of gastric mucosal blood vessels via improving the gastric mucosal blood flow and elevating the defensive factors nitric oxide (NO) and prostaglandin E2 (PGE2), and lowering the level of vasoconstrictor factor endothelin (ET)-1. Wheat peptides exhibited anti-inflammatory reaction through decreasing inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, and increasing trefoil factor 1 (TFF1) levels. Moreover, wheat peptides significantly down-regulated the expression of phosphorylated nuclear factor kappa-B (p-NF-κB) p65 proteins in the NF-κB signaling pathway. Altogether, wheat peptides protect gastric mucosa from ethanol-induced lesions in rats via improving the gastric microcirculation and inhibiting inflammation mediated by the NF-κB signaling transduction pathway.

1377 Gastric Necrosis Associated With Necrotizing Pancreatitis

INTRODUCTION: Acute pancreatitis may lead to local complications and systemic toxicity. Gastric necrosis is a rare complication with only few cases reported in the literature. Herein we present a case of severe acute necrotizing pancreatitis acute complicated by gastric necrosis. CASE DESCRIPTION/METHODS: Our patient is a 42-year-old male with a history of idiopathic recurrent necrotizing pancreatitis who presented with severe epigastric abdominal pain, nausea and vomiting. Previous imaging revealed pancreatic necrosis in the body and head of the pancreas and extensive splanchnic thrombosis. Labs showed normal blood count, lipase and complete metabolic panel. CT of the abdomen during this admission revealed large volume ascites and total pancreatic necrosis and multiple areas of low attenuation in the expected location of the pancreatic head and body (Figure 1). Despite supportive care and antibiotics, he was unable to tolerate oral intake. On day 14 he developed hematemesis and hypotension. His hemoglobin dropped to 9.3 g/dL from 13.3 g/dL. An abdominal x-ray revealed a curvilinear lucency overlying the left lateral upper stomach suggestive of gastric pneumatosis. Upper endoscopy showed erythema, edema, and severe ulcerations with black necrotic mucosa in the inferior and posterior walls of the stomach. The anterior wall was relatively spared with clear demarcation of ischemic and viable mucosa (Figure 2). Gastric biopsies confirmed gastric necrosis. The patient's hemodynamic status worsened, and he required vasopressor support. Further interventions were deferred given his comorbidities and worsening hemodynamic status, and he was discharged to hospice care. DISCUSSION: Gastric necrosis is a rare complication of acute pancreatitis and occurs due to severe reduction in gastric mucosal blood flow. This can be secondary to thrombosis of large vessels such as the celiac trunk or attributed to microcirculatory vasospasm due to the release of thrombogenic and inflammatory mediators. The development of gastric necrosis leads to further clinical deterioration in a clinically ill patient. Despite its rarity, gastric necrosis should be suspected in the setting of severe pancreatitis in patients with signs of gastrointestinal bleeding and clinical deterioration.

Research progress of traditional Chinese medicine in the treatment of gastric mucosa injury caused by long-term use of low dose aspirin in patients with coronary heart disease

Aspirin is widely used in the treatment and prevention of coronary heart disease (CHD). It plays an important role in anti-platelet aggregation by inhibiting the activity of cyclooxygenase-1 (COX-1). On the other hand, the decrease of COX-1 activity inhibits the production of prostaglandin (PG) in gastric mucosa, which leads to the decrease of gastric mucosal blood flow and the weakening of mucous barrier. That makes the gastric mucosa more vulnerable to injury. We usually treat gastric mucous injury caused by long-term use of low-dose-aspirin (LDA) with drugs that inhibit gastric acid secretion. However, these drugs cannot improve gastric mucosal blood flow and the effect of gastric mucous barrier. And the long-term use of these drugs can lead to a variety of adverse reactions, such as dyspepsia, osteoporosis, nutritional deficiency and so on. This paper reviews the research progress of traditional Chinese medicine (TCM) in the treatment of gastric mucosa injury caused by LDA. It was found that Panax quinquefolius ( Xiyangshen ) saponins, Astragaloside A, Dendrobium officinale ( Tiepishihu ) polysaccharide, Bletilla Striata ( Baiji ), Jinghua Weikang capsule, Danhong injection and other TCM components or preparations can increase the level of PG in gastric mucosa and increase the blood flow of gastric mucosa, so as to improve the effect of gastric mucous barrier. This provides a certain idea for the prevention and treatment of gastric mucosa injury caused by long-term application of LDA in patients with CHD.

Weiqi Decoction Attenuated Chronic Atrophic Gastritis with Precancerous Lesion through Regulating Microcirculation Disturbance and HIF-1α Signaling Pathway.

Aim Chronic atrophic gastritis (CAG), the precancerous lesions of gastric cancer, plays an important role in the stepwise process of gastric cancer. The ancient Chinese medicine believes in that Qi deficiency and blood stasis are involved in the pathogenesis of CAG. Weiqi decoction, a classical formula from Longhua Hospital, could supplement Qi and activate blood circulation of human beings and has been used for treating CAG in clinic over twenty years. The study aims to clarify the effect and underlying molecular mechanism of Weiqi decoction on CAG rats. Methods Forty-eight male Wistar rats were divided randomly into six groups: control group, model group, folic acid group, and WQD-treated groups at doses of 4 g/kg, 2 g/kg, and 1 g/kg, with eight rats in each group. MNNG and saturated NaCl were used to induce CAG rat with precancerous lesion (intestinal metaplasia and dysplasia). After 40 weeks, gastric mucosal blood flow was measured using Laser Doppler Flowmetry. The pathological changes of the gastric mucosa were identified by H&E staining and AB-PAS staining. The protein expression of COX-2, HIF-1α, VEGFR1, VEGFR2, Ki67, and cleaved caspase 3 in the gastric tissues was measured by western blotting approach. Gene expression of COX-2, HIF-1α, VEGF, VEGFR1, VEGFR2, Ang-1, and Ang-2 was detected by using Quantitative PCR method. The PGE2 concentrations in serum were detected by ELISA method. The protein expression of Ki67 in gastric mucosa was also detected by immunohistochemistry. Results Compared with control rats, atrophy and intestinal metaplasia as well as the microcirculation disturbance of gastric mucosa were induced in the stomach of CAG rats identified by the H&E and AB-PAS staining as well as microcirculation measurement, which could be significantly attenuated by WQD treatment. Moreover, compared with the control group, the protein and gene expression of COX-2, HIF-1α, VEGFR1, and VEGFR2 in gastric tissues of pylorus was obviously increased and the serum PGE2 level was significantly deceased in CAG rats, which could be significantly counteracted by WQD administration. However, the gene expression of Ang-1 and Ang-2 was not significant difference between control rats and CAG rats, and WQD also had no significant effect on the gene expression of Ang-1 and Ang-2. Furthermore, the increased cell proliferation marked by upregulated protein expression of Ki67 and decreased cell apoptosis marked by downregulated protein expression of cleaved caspase 3 in stomach of pylorus in CAG rats were obviously reversed by WQD treatment. Conclusion WQD attenuated CAG with precancerous lesion through regulating gastric mucosal blood flow disturbance and HIF-1α signaling pathway.

Therapeutic effect of total triterpenoids of Chaenomeles speciosa combined with omeprazole on gastric ulcer induced by indomethacin in rats

The aim of this paper was to observe the combination therapy with total triterpenoids of Chaenomeles speciosa and omeprazole on indomethacin-induced gastric ulcer in rats, and explore its possible mechanism. Rats were randomly divided into normal group, model group, omeprazole monotherapy(3.6 mg·kg~(-1)) group, total triterpenoids of C. speciosa monotherapy(100 mg·kg~(-1)) group, total triterpenoids of C. speciosa and omeprazole combination therapy(100 mg·kg~(-1)+3.6 mg·kg~(-1)) group. Except for the normal group, the other groups were given indomethacin(20 mg·kg~(-1)) by oral once a day for 7 consecutive days. Then the treated groups were given corresponding drugs by gavage, once a day for 14 consecutive days. The next day after the last administration, half of the rats in each group were measured the gastric mucosal blood flow, gastric juice volume and serum TNF-α, IL-1β, IL-6, IL-4 and IL-10. After the remaining rats in each group were underwent pyloric ligation 4 hours after the last administration, the gastric endocrine volume, pH value and total acidity of gastric secretion were measured, then histological analysis was performed, MPO activity, cAMP content and histomorphological analysis were conducted. Real-time PCR was applied to detect the mRNA expressions of gastric tissue TNF-α,IL-1β, IL-6, IL-4, IL-10, VEGFA, A_(2A)R; the protein expressions of VEGFA, A_(2A)R, PKA, p-PKA, CREB, p-CREB, EGF, EGFR, p-EGFR, MUC6, TFF2 in gastric tissue were detected by Western blot. The results indicated that total triterpenoids of C. speciosa and omeprazole combination therapy might significantly increase gastric mucosal blood flow, gastric mucus volume, reduce gastric endocrine volume, secretion acidity and mucosal damage, decrease the levels of TNF-α,IL-1β and IL-6, increase the levels of IL-4 and IL-10 in blood and gastric tissue, inhibit the activity of MPO, increase the content of cAMP in gastric tissue, up-regulate the mRNA expressions of VEGFA, A_(2A)R and protein expressions of VEGFA, A_(2A)R, PKA, p-PKA, CREB, p-CREB, EGF, EGFR, p-EGFR, MUC6, TFF2 in gastric tissue, elevate p-PKA/PKA, p-CREB/CREB and p-EFGR/EFGR. Moreover, the combination therapy with total triterpenoids of C. speciosa and omeprazole was more obvious than those of two monotherapies. These aforementioned findings suggested that the combination therapy with total triterpenoids of C. speciosa and omeprazole on indomethacin-induced gastric ulcer have significant therapeutic effect on indomethacin induced gastric ulcer in rats, its mechanism might be related to regulating A_(2A)R/AKT/CREB, A_(2A)R/VEGFA, EGF/EGFR and MUC6/TFF2 signaling pathways, inhibiting pro-inflammatory factors, increasing gastric mucosal blood flow, up-regulating mucosal cell proliferation factors and promoting mucosal protective factors.

The effects of antibacterial mouthwash on the oral microbiome: potential consequences for intensive care patients

The role of the oral microbiome in maintaining health is becoming increasingly apparent (1). Oral nitrate-reducing commensal bacteria reduce nitrate to nitrite, which is then reduced to nitric oxide in the acidic environment of the stomach via the nitrate-nitrite-nitric oxide pathway. Nitric oxide has a key role in maintaining gastric mucosal blood flow and thickness, thereby protecting against bacterial infection. Gastric nitric oxide levels are nearly abolished in intubated and ventilated intensive care patients, which might be linked to the prevalence of ulcers and bacterial overgrowth (2). In addition, it has been reported that the nitrate content of both enteral and parenteral nutrition is minimal (3) thereby further reducing the activity of the nitrate-nitrite-nitric oxide pathway. Patients on intensive care may receive salivary suction, antibacterial mouthwash, low nitrate feeds and broad-spectrum antibiotics, all of which could affect the oral microbiome. Poor oral health and periodontal disease is associated with ventilator-associated pneumonia (4). As part of a wider study we investigated the effects of antibacterial mouthwash on oral nitrate-reducing capacity and salivary pH, glucose and lactate as well as salivary and plasma nitrate and nitrite concentrations.

The role of hydrogen sulfide in gastric mucosal damage

Gastrointestinal disease is a major global threat to public health. In the past few decades, numerous studies have focuses on the application of small molecule gases in the disease treatment. Increasing evidence has shown that hydrogen sulfide (H2S) has anti-inflammatory and anti-oxidative effects, and can regulate gastric mucosal blood flow in the gastric mucosa. After gastric mucosa damage, the level of H2S in the stomach decreases. Administration of H2S can protect and repair the damaged gastric mucosa. Therefore, H2S is a new target for the repair and treatment of gastric mucosa damage. In this review, we introduce the roles of H2S in the treatment of gastric mucosa damage and provide the potential strategies for further clinical treatment.

Gastroprotective effect of araloside A on ethanol- and aspirin-induced gastric ulcer in mice: involvement of H+/K+-ATPase and mitochondrial-mediated signaling pathway.

The aim of this study was to elucidate the gastroprotective activity and possible mechanism of involvement of araloside A (ARA) against ethanol- and aspirin-induced gastric ulcer in mice. The experimental mice were randomly divided into control, model, omeprazole (20mg/kg, orally) and ARA (10, 20 and 40mg/kg, orally). Gastric ulcer in mice was induced by intragastric administration of 80% ethanol (10mL/kg) containing 15mg/mL aspirin 4h after drug administration on day 7. The results indicated that ARA could significantly raise gastric juice volume and acidity; ameliorate gastric mucosal blood flow, gastric binding mucus volume, ulcer index and ulcer inhibition rate; suppress H+/K+-ATPase activity, which was confirmed by computer-aided docking simulations; inhibit the release of mitochondrial cytochrome c into the cytoplasm; inhibit caspase-9 and caspase-3 activities and down-regulate mRNA expression levels; down-regulate the mRNA and protein expressions of apoptosis protease-activating factor-1 and protein expression of cleaved poly(ADP ribose) polymerase-1; and up-regulate Bcl-2 mRNA and protein expressions and down-regulate Bax mRNA and protein expressions, thus elevating the Bcl-2/Bax ratio in a dose-dependent manner. Histopathological observations further provided supportive evidence for the aforementioned results. The results demonstrated that ARA exerted beneficial gastroprotective effects on alcohol- and aspirin-induced gastric ulcer in mice, which was related to suppressing H+/K+-ATPase activity as well as pro-apoptotic protein expression, and promoting anti-apoptotic protein expression, thus alleviating gastric mucosal injury and cell death.

Effects of intracerebroventricularly injected glucagon-like peptide-2 on ethanol-induced gastric mucosal damage in rats

ABSTRACTPurpose: The present study aims to investigate the effects of intracerebroventricularly (i.c.v.)-injected glucagon-like peptide-2 (GLP-2) on ethanol-induced gastric mucosal damage and to reveal the mechanisms involved in this effect.Materials and Methods: Rats received absolute ethanol orally via an orogastric tube 30 minutes after GLP-2 (1–200 ng/10 µl; i.c.v.) or saline (10 µl) injections. They were decapitated 1 hour later, their stomachs were removed, and the gastric mucosal damage was scored.Results: A total of 100 ng GLP-2 inhibited the gastric mucosal damage by 67%. This effect was abolished by the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) (10 µg/kg; s.c.), but was not affected by either the nitric oxide (NO) synthase inhibitor L-NAME (30 mg/kg; s.c.) or the cyclooxygenase inhibitor indomethacin (5 mg/kg; i.p.). The most effective gastroprotective dose of GLP-2 (100 ng/10 µl; i.c.v.), but not the higher doses (150 or 200 ng/10 µl; i.c.v.) prevented the decrease in gastric mucosal blood flow caused by ethanol.In conclusion, i.c.v. GLP-2 protects against ethanol-induced gastric mucosal damage and this effect is mediated by CGRP receptor activation and gastric mucosal blood flow, but not by NO or prostaglandins.

Protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice.

ABSTRACTRadon therapy using radon (222Rn) gas is classified into two types of treatment: inhalation of radon gas and drinking water containing radon. Although short- or long-term intake of spa water is effective in increasing gastric mucosal blood flow, and spa water therapy is useful for treating chronic gastritis and gastric ulcer, the underlying mechanisms for and precise effects of radon protection against mucosal injury are unclear. In the present study, we examined the protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice. Mice inhaled radon at a concentration of 2000 Bq/m3 for 24 h or were provided with hot spring water for 2 weeks. The activity density of 222Rn ranged from 663 Bq/l (start point of supplying) to 100 Bq/l (end point of supplying). Mice were then orally administered ethanol at three concentrations. The ulcer index (UI), an indicator of mucosal injury, increased in response to the administration of ethanol; however, treatment with either radon inhalation or hot spring water inhibited the elevation in the UI due to ethanol. Although no significant differences in antioxidative enzymes were observed between the radon-treated groups and the non-treated control groups, lipid peroxide levels were significantly lower in the stomachs of mice pre-treated with radon or hot spring water. These results suggest that hot spring water drinking and radon inhalation inhibit ethanol-induced gastric mucosal injury.

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.