Basal Acid Secretion Research Articles

Discovery of novel benzimidazole derivatives as potent potassium-competitive acid blockers for the treatment of acid-related diseases

H+, K+-ATPase, as the most critical enzyme in gastric acid secretion, has long been an attractive target for the treatment of acid-related diseases. In this study, a series of benzimidazole derivatives were designed and synthesized through conformational restriction and skeleton hopping strategies by using vonoprazan as the lead compound. Among them, compounds A12 (IC50 = 9.32 μM) and A18 (IC50 = 5.83 μM) showed better inhibition at the enzyme level. In addition, gastric acid secretion inhibition was assessed in vivo, and the results showed that A12 and A18 significantly inhibited basal gastric acid secretion, 2-deoxy-d-glucose (2DG) stimulated gastric acid secretion and histamine-stimulated gastric acid secretion. In further in vitro metabolic experiments, A12 and A18 demonstrated excellent stability and low toxicity. Pharmacokinetic studies showed that the p.o. and i.v. half-lives of A18 were 3.21 h and 8.67 ± 1.15 h, respectively. In summary, A18 might be a novel and effective potassium-competitive acid blocker, and this study provides strong support for it use in the treatment of acid-related diseases.

Gastric acid anti-secretory activity of aqueous leaf extract of Hypoestes rosea in ulcer-induced rats

Background: Hypoestes rosea, an evergreen shrub belonging to the Acanthaceae family possess antiulcer potential amongst its several other medicinal properties, including usefulness as anti-diabetic and anti-inflammatory agents. Objective: In this study, we investigated the anti-secretory effect of aqueous leaf extract of H. rosea as the possible mechanism for its antiulcer activity in gastric ulcer induced rats. Methods: 40 rats were divided into 2 experimental phases of 20 rats each. They were further separated into 5 groups as follows: Group 1 (Normal control: rat chow and water only). Group 2 Ulcer control: Indomethacin-induced (40mg/kg bw). Group 3: Low dose (100mg/kg bw). Group 4: Medium dose (200mg/kg bw). Group 5: High dose (300mg/kg bw). Phase 1 involved determination of ulcer lesion index and % inhibition. Phase 2 involved estimation of gastric acid secretion using the method of continuous perfusion with 10minutes aliquots titrated against 0.01N NaOH. Results: Aqueous extract of Hypoestes rosea produced a significant (P<0.05) dose-dependent decrease in ulcer lesion score with an accompanying increase in percentage inhibition at the various doses used in the study (100, 200 and 300 mg/kg bw). Also, there was a significant decrease in basal and histamine-induced acid secretion at all doses with the greatest effect observed at the high dose (300mg/kg bw). Conclusion: Results obtained showed that aqueous extract of H. rosea decreased gastric acid secretion possibly due to inhibition of Histamine receptors and may thus be the mechanism for its anti-ulcer activity.

Proton pumps inhibitors in gastroesophageal reflux disease: what is the best regimen? A based evidence review

Objectives: Gastroesophageal reflux disease is one of the most common gastrointestinal diagnoses. This disorder causes many symptoms and may induce the development of Barret’s esophagus and esophageal adenocarcinoma. Proton pump inhibitors are the most used treatment and, usually, are prescribed for once-daily dosing before breakfast. However, many patients describe night-time symptoms, a period when an increase of basal gastric acid secretion occurs. Therefore, this evidence-based review was performed in order to understand which is the best regimen for proton pump inhibitor intake. Methods: The MeSH words ‘proton pump inhibitors’, ‘gastro-oesophageal reflux’, GERD, and pH were chosen to search for synopses, guidelines, meta-analysis, systematic reviews, and original papers, published after 2008 in the databases MEDLINE, National Guideline Clearinghouse, NHS Evidence, Canadian Medical Association, TRIP Database, The Cochrane Library, DARE and Bandolier in English, French, Spanish and Portuguese. A search in the Índex de Revistas Médicas Portuguesas with the words “inibidores das bombas de protões”, “refluxo gastroesofágico”, DRGE, and pH was also performed. The search retrieves 2,546 articles, from those, three were used in this review. Results: Three prospective studies that evaluate the effects of dosage and/or timing of proton pump inhibitors intake in gastric pH were obtained. These studies indicate that, in patients with predominant night-time symptoms, intake before dinner achieves better results than before breakfast. Additionally, doubling the dose reduces symptoms and the time of pH lower than four. Conclusion: Symptom timing and patient compliance are crucial when choosing the therapeutic regimen. The timing of proton pumps inhibitors intake should be associated with the symptom’s timing; C-level of recommendation.

Sham Feeding Induced Gastric Acid Secretion in Patients with Caustic Induced Esophageal Stricture.

Caustic ingestion can lead to structural changes in the upper gastro-intestinal tract. However, there is limited data on the effect of caustic ingestion on gastric secretion. This study was planned to determine changes in gastric acid output after sham feeding in patients with caustic induced esophageal stricture and to compare it with healthy controls. It was a prospective study done at tertiary care center in North India. Consecutive patients with caustic induced esophageal stricture were evaluated for the study. Gastric secretory function was estimated in the basal state and after modified sham feeding. These results were compared withage-matched controls. The mean age of the included patients (n = 18) was 30.11 ± 9.19years and 13 patients were male. 16 (88%) patients had history of acid ingestion. Patients with caustic sequelae had significantly lower basal and stimulated acid secretion compared to controls (n = 10) (5.84 ± 2.44mmol/hr; p < 0.01 and 17.16 ± 7.53mmol/hr; p < 0.01; respectively). Patients with lower esophageal stricture (n = 8) had significantly lower increase in acid output compared to patients with stricture elsewhere in esophagus (0.20 ± 0.3 vs. 2.31 ± 1.74mmol/hr, p < 0.01). Patients with lower esophageal involvement had significantly lower stimulated acid secretion and increase in acid secretion compared to controls (4.74 ± 4.67 vs. 17.16 ± 7.53mmol/hr; p < 0.01 and 20 ± 0.3 vs. 2.09 ± 0.88mmol/hr; p < 0.01; respectively).

Effects of Bambara Nut (Vigna subterranean) on Basal and Stimulated Gastric Acid Secretion due to Histamine, Pentagastrin and Carbachol in rats

The seed extracts of V. subterranean (Bambara nuts) have many therapeutic applications in folkloric medicine owing to their effective secondary metabolites such as alkaloids, flavonoids, saponins, resins, and glycosides (Andzouana et al., 2014). The infusions and decoctions of the seeds are used to treat venereal diseases, diarrhoea, cataract, beriberi and polymenorrhea (Brink and Belay, 2006; Basu et al., 2007). The raw seeds are chewed to alleviate nausea and vomiting in pregnant women. V. Subterranea seed extracts have been shown to possess some biological properties such as antioxidant and hepatoprotective (Nyau et al., 2015; Iweala and Elekwa, 2001). In spite of multi‐functional properties of V. subterranea, its gastroprotective effect has not been fully explored. This study was carried out to examine the effects of V. Subterranea on basal and stimulated gastric acid secretion (GAS) in the Wistar rats. Each group of rats consisting of 5 rats (180–210g) was treated with aqueous extract of V. Subterranea (150 mg/kg, 250mg/kg and 400mg/kg) orally for 21 days. The animals were handled in accordance with guide for the care and use of laboratory animals (NIH, 2011). At the last day of the treatment, the rats were fasted for 24 hours, anaesthetized with ketamine. GAS (mEq/l) induced by histamine, carbachol and pentagastrin administration were assessed by the continuous perfusion technique using phenolphthalein as indicator. Data obtained were expressed as the Mean ± SEM) and analyzed using one way Analysis of Variance (ANOVA) and Graph Pad prism 5. The differences in mean were considered significant at p≤ 0.05. The aqueous extract of V. Subterranea significantly decreased (p&lt;0.05) GAS induced by the histamine, carbachol and pentagastrin in a dose‐dependent manner over 80 minutes period in all the treated groups, although at varying rates. The gastroprotective action of V. Subterranea may be multifactorial that may include an anti‐secretory action.Support or Funding InformationWe wish to thank Usmanu Danfodiyo University, Sokoto, Nigeria for their support.Effect of Histamine on BambaraFigure 1Effect of Carbachol on BambaraFigure 2Effect of Pentagastrin on BambaraFigure 3

Helicobacter pylori And Duodenal Ulcer: Systematic Review Of Controversies In Causation.

BackgroundThere are controversies on the causal role of H. pylori in duodenal ulceration. Helicobacter pylori are curved gram-negative microaerophilic bacteria found at the layer of gastric mucous or adherent to the epithelial lining of the stomach. It’s a public health significance bacteria starting from discovery, and the prevalence and severity of the infection varies considerably among populations. H. pylori are a risk for various diseases, while the extent of host response like gastric inflammation and the amount of acid secretion by parietal cells affects the outcome of infection.MethodRelevant literature were searched from databases such as Google Scholar, PubMed, Hinari, Web of Science, Scopus, and Science Direct.ResultThe review evidence supports a strong causal relation between H. pylori infection and duodenal ulcer, as patients are more likely to be infected by virulent strains which later cause duodenal ulceration. Thus, eradication of H. pylori infection decreases the incidence of duodenal ulcers, and prevents its recurrence by reducing both basal gastrin release and acid secretion without affecting parietal cell sensitivity. On the other hand, some studies show that H. pylori infection is not associated with the development of duodenal ulcers and such a lack of association revealed that duodenal ulceration has different pathogenesis.ConclusionDespite controversies observed in the causal role of H. pylori to duodenal ulceration by various studies, Hill criteria of causation proved the presence of a causal relation between H. pylori infection and duodenal ulcers. Other factors are also responsible for the development of duodenal ulcers and such factors are responsible for the differences in the prevalence of the diseases.

STUDY OF ANTISECRETORY ACTIVITY OF DINITRATE 2-PHENYL-9-DIETHYLAMINOETHYLimidazo[1,2-A] BENZIMIDAZOLE BY METHOD OF CONTINUOUS PERFUSION OF RATS’ STOMACHS

Nowadays, effective pharmacotherapy of acid-dependent gastrointestinal diseases remains an urgent problem of modern gastroenterology. In this regard, the search for new drugs with a pronounced antisecretory activity still continues; their aim is to keep the control over the acid production safe and effective.The aimof this study was an experimental study of the antisecretory activity of the substance and the finished dosage form (FDF) of dinitrate 2-phenyl-9-diethylaminoethylimidazo[1,2-a]benzimidazole.Materials and Methods.The study of antisecretory activity was performed by method of a continuous perfusion of rats’ stomachs. The studied substance was administered at the doses of 3, 10 and 30 mg/kg, and the FDF – at the doses of 13 and 26 mg/kg. The substance of Ranitidine (Sigma Аldrich, USA) was used as a reference object in the study of the antisecretory activity of the substance under study, and Ranitidine (Hemofarm A.D., Serbia) was used as a reference drug in the study of the FDF. In order to determine the stimulated secretion immediately before collecting the samples of the perfusate, histamine was administered subcutaneously at the dose of 5 mg/kg. The content of hydrochloric acid in the perfusate was determined by titration of a 0.01 M sodium hydroxide solution. The acidity value was determined in terms of the debit-hour of hydrochloric acid.Results and discussion.The obtained experimental data showed that the studied substance at the dose of 30 mg/kg decreased the basal hydrochloric acid secretion by 54%, which significantly exceeded the antisecretory effect of Ranitidine by 1.8 times. The FDF at the dose of 26 mg/kg, statistically reliable relative to the control and the group treated with Ranitidine, decreased the basal secretion of gastric juice by 33%. The substance at the dose of 30 mg/kg reliably suppressed the stimulated secretion of hydrochloric acid by 80%, while Ranitidine did it by 56%. The FDF at the dose of 26 mg/kg decreased the histamine-stimulated secretion by 66%, and Ranitidine did it by 52%, which was statistically reliable.Сonclusions.The studied substance and its dosage form are more effective in suppressing basal activities and exceed the anisecretory activity of H2 -histamine antagonists of Ranitidine under the conditions of the secretion stimulated by histamine.

KFP-H008 blocks gastric acid secretion through inhibiting H+-K+-ATPase

1-(5-(1H-indol-5-yl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine (KFP-H008)，a novel and potent potassium-competitive acid blocker for the treatment of acid secretion related diseases, has not been reported previously. In this study, we demonstrated that KFP-H008 inhibits basal acid secretion, 2-deoxy-D-glucose- (2DG-) stimulated gastric acid secretion in rats. KFP-H008 blocked histamine-stimulated acid secretion in rats and heidenhain pouch dogs and reversed acid output in isolated gastric perfusion under histamine stimulation. In all the animal experiments, KFP-H008 exerted a more effective, potent and longer-lasting inhibitory action in comparison with lansoprazole, a proton pump inhibitor (PPI) commonly used in clinic. KFP-H008 inhibited H+-K+-ATPase activity both at pH 6.5 and pH 7.5, and was unaffected by pH. The inhibitory action was reversible and was achieved in a K+-competitive manner. Furthermore, KFP-H008 did not affect Na+-K+-ATPase activity, thus exhibiting high selectivity, which is different from PPIs. In all, KFP-H008, a novel potassium-competitive acid blocker, may provide new option for the patients with acid-related diseases and provide longer-lasting inhibitory action than drugs commonly used in clinical treatment.

Healing and Antisecretory Effects of Aqueous Extract of Eremomastax speciosa (Acanthaceae) on Unhealed Gastric Ulcers.

Objective This work investigated the healing and antisecretory effects of the aqueous extract of Eremomastax speciosa on “unhealed gastric ulcers” associated with gastric acid hypersecretion. Materials and Methods “Unhealed gastric ulcers” were induced using indomethacin following the establishment of acetic-acid-induced chronic gastric ulcers. The extract (200 and 400 mg/kg, per os) was administered concomitantly with indomethacin (1 mg/kg, subcutaneously). The effects of the extract on both basal and histamine-stimulated gastric acid secretion were determined. Mucus secretion and oxidative stress parameters were measured, and histological assessment of ulcer healing was carried out. Results The extract significantly promoted the healing process in rats subjected to “unhealed gastric ulcers” (82.4–88.5% healing rates). Treatment with the extract significantly reduced the basal (25.95–49.51% reduction rates) and histamine-stimulated (24.25–47.41%) acid secretions. The healing effect of the extract was associated with a significant (p < 0.05) increase of mucus secretion and concentrations of antioxidant enzymes compared with the controls. The extract at the highest dose showed normalization of the mucosa, without glandular destruction and with the disappearance of fibrosis and lymphocyte infiltration. Conclusion The abilities of the extract to increase mucus secretion, to reinforce antioxidant status, and to inhibit acid secretion would be some of the mechanisms by which this extract would accelerate the healing process in “unhealed gastric ulcers.”

Nitric Oxide and Hydrogen Sulfide Interact When Modulating Gastric Physiological Functions in Rodents.

The objective was to evaluate the effects of nitric oxide (NO) and hydrogen sulfide (H2S) donors and possible interactions between these two systems in modulating gastric function. Mice received saline, sodium nitroprusside (SNP), or sodium hydrosulfite (NaHS), and after 1h, the animals were killed for immunofluorescence analysis of CSE or eNOS expressions, respectively. Other groups received saline, SNP, NaHS, Lawesson's reagent (H2S donor), PAG+SNP, L-NAME, L-NAME+NaHS, or L-NAME+Lawesson's reagent. Then, the gastric secretions (mucous and acid), gastric blood flow, gastric defense against ethanol, and gastric motility (gastric emptying and gastric contractility) were evaluated. SNP and NaHS increased the expression of CSE or eNOS, respectively. SNP or Lawesson's reagent did not alter gastric acid secretion but increased mucus production, and these effects reverted with PAG and L-NAME treatment, respectively. SNP or NaHS increased gastric blood flow and protected the gastric mucosa against ethanol injury, and these effects reverted with PAG and L-NAME treatments, respectively. SNP delayed gastric emptying when compared with saline, and PAG partially reversed this effect. NaHS accelerate gastric emptying, and L-NAME partially reversed this effect. SNP and NaHS alone induced gastric fundus and pylorus relaxation. However, pretreatment with PAG or L-NAME reversed these relaxant effects only in the pylorus but not in the gastric fundus. NO and H2S interact in gastric physiological functions, and this "cross-talk" is important in the control of mucus secretion, gastric blood flow, gastric mucosal defense, and gastric motility, but not in the control of basal gastric acid secretion.

Novokinin inhibits gastric acid secretion and protects against alcohol-induced gastric injury in rats.

Novokinin (Arg-Pro-Leu-Lys-Pro-Trp), a potent vasorelaxing and hypotensive peptide modified from ovokinin, exhibits highly selective affinity for the AT2 receptor. However, its role in gastrointestinal functions is still not fully understood. In this study, we found that novokinin inhibited basal gastric acid secretion and protected gastric mucosa from alcohol-induced injury in a dose-related manner in rats after intracerebroventricular (i.c.v.) administration. Novokinin significantly decreased basal gastric acid output at the dose of 50 and 100nmol/rat. The effect of novokinin on gastric acid secretion was reversed by central injection of PD 123319 (10nmol/rat), an AT2 receptor antagonist, and peripheral injection of indomethacin (10mg/kg), an inhibitor of prostaglandin synthesis. Meanwhile, pre-treatment with novokinin at doses of 10, 50, and 100nmol/rat significantly reduced the alcohol-induced gastric mucosal injury compared to the ulcer-control group, which was inhibited by indomethacin (10mg/kg). The result showed a remarkable increase in the level of prostaglandin E2 (PGE2), glutathione (GSH), and a decrease in malondialdehyde (MDA) after i.c.v. administration of novokinin. These findings suggest that the inhibitory effect of novokinin on gastric acid secretion is probably mediated via an AT2 receptor-prostaglandins (PGs) pathway. The gastroprotective effect of novokinin might be attributed to the inhibition of acid secretion, the cytoprotection of PGs, and the antioxidant property.

Gastric antiulcer, antisecretory and cytoprotective properties of celery (Apium graveolens) in rats

Celery seed is generally regarded as safe for human consumption as a spice, natural seasoning and plant extract/essential oil. 500 grams of the shade dried aerial parts of celery was coarse powdered and macerated in 3 liters of 96% ethanol for 72 hours using percolation method. Wistar albino rats were used. Celery extract produced a dose-dependent significant protection against the ulcerogenic effect induced by indomethacin. In the ethanol and strong alkali-induced ulcer protocol, it was observed that the treatment with ethanolic extract of celery (250 and 500 mg/kg) significantly reduced the lesion index. A highly significant reduction of ulceration in rats' stomach and intraluminal bleeding was recorded after celery extract pretreatment of the dose of 500 mg./kg orally. In the gastric secretion determination model, using ligated pylorus for 6h, the treatment with celery extract (250 and 500 mg/kg i.p.), reduced the volume of the basal gastric secretion, titratable acidity and ulceration significantly in comparison with control group. The results show that ethanol extract of celery displays gastroprotective activity, as demonstrated by its significant inhibition of the formation of ulcers induced by different experimental models and its ability to decrease basal gastric acid secretion. This gastric antiulcer capacity of celery extract could be related to its antioxidant properties, resulting in reduction of the lipid peroxidation and elevation of the NP-SH contents, besides improving mucus coat of the stomach. Therefore, we suggest that due to its antioxidative effects, it may be useful in the prevention of gastric disorders.

Effect of netazepide, a gastrin/CCK2 receptor antagonist, on gastric acid secretion and rabeprazole-induced hypergastrinaemia in healthy subjects.

To compare gastric acid suppression by netazepide, a gastrin/CCK2 receptor antagonist, with that by a proton pump inhibitor (PPI), and to determine if netazepide can prevent the trophic effects of PPI-induced hypergastrinaemia. Thirty healthy subjects completed a double-blind, randomized, parallel group trial of oral netazepide and rabeprazole, alone and combined, once daily for 6 weeks. Primary end points were: basal and pentagastrin-stimulated gastric acid and 24 h circulating gastrin and chromogranin A (CgA) at baseline, start and end of treatment, gastric biopsies at baseline and end of treatment and basal and pentagastrin-stimulated gastric acid and dyspepsia questionnaire after treatment withdrawal. All treatments similarly inhibited pentagastrin-stimulated gastric acid secretion. All treatments increased serum gastrin, but the combination and rabeprazole did so more than netazepide alone. The combination also reduced basal acid secretion. Rabeprazole increased plasma CgA, whereas netazepide and the combination reduced it. None of the biopsies showed enterochromaffin-like (ECL) cell hyperplasia. Withdrawal of treatments led neither to rebound hyperacidity nor dyspepsia. Netazepide suppressed pentagastrin-stimulated gastric acid secretion as effectively as did rabeprazole. The reduction in basal acid secretion and greater increase in serum gastrin by the combination is consistent with more effective acid suppression. Despite our failure to show rabeprazole-induced ECL cell hyperplasia and rebound hyperacidity, the increase in plasma CgA after rabeprazole is consistent with a trophic effect on ECL cells, which netazepide prevented. Thus, netazepide is a potential treatment for the trophic effects of hypergastrinaemia and, with or without a PPI, is a potential treatment for acid-related conditions.

Gastric antiulcer, antisecretory and cytoprotective properties of celery (Apium Graveolens) in rats

Celery seed is generally regarded as safe for human consumption as a spice, natural seasoning and plant extract/essential oil. The present study was carried out to assess the possible anti-gastric ulcer, cytoprotective and antisecretory properties of ethanolic extracts of Apium graveolens in rats in order to substantiate the traditional Unani System of Medicine. Five hundred grams of the shade dried aerial parts of celery was coarse powdered and macerated in 3 liters of 96% ethanol for 72 hours using a percolation method. Wistar albino rats were used. Celery extract produced a dose-dependent significant protection against the ulcerogenic effect induced by indomethacin. In the ethanol and strong alkali-induced ulcer protocol, it was observed that the treatment with ethanolic extracts of celery (250 and 500 mg/kg) significantly reduced the lesion index. A highly significant reduction of ulceration in rats' stomach and intra-luminal bleeding was recorded after celery extract pretreatment at the dose of 500 mg/kg orally. In the gastric secretion determination model, using ligated pylorus for 6 h, the treatment with celery extract (250 and 500 mg/kg i.p.), reduced the volume of basal gastric secretion, titratable acidity and ulceration significantly in comparison with a control group. The results show that ethanol extract of celery displays gastroprotective activity, as demonstrated by its significant inhibition of the formation of ulcers induced by different experimental models, and its ability to decrease basal gastric acid secretion. This gastric antiulcer capacity of celery extract could be related to its antioxidant properties, resulting in reduction of the lipid peroxidation and elevation of the NP-SH contents, besides, improving the mucus coat of the stomach. Therefore, we suggest that due to its antioxidative effects, it may be useful in the prevention of gastric disorders.

Exendin Increases Gastric Acid Secretion in the Anesthetized Rat

The objective of the current study was to assess the effect of the anti‐diabetic peptide, exenatide (Byetta®), on gastric acid secretion in the rat. Fasted rats were anesthetized and cannulas placed in esophagus (timed stomach secretion sampling), femoral artery (blood pressure monitoring), carotid artery (timed blood sampling). Phenol red was injected via the esophageal cannula and recovered every 10 minutes. Stomach aspirates were assessed for phenol red content (gastric emptying), pH, and titrated to pH 7.0 to calculate umoles of acid recovered. Exendin (up to 150 ug/kg) or vehicle were administered as a subcutaneous bolus at time zero, and stomach contents and blood were collected every 10 minutes for the subsequent 90 minutes. At 90 minutes, a pentagastrin bolus (~250 ug SC) was administered to confirm integrity of parietal cell responsiveness to pharmacologic stimulation of acid secretion. Basal acid secretion rate in the anesthetized rat (~1‐3 umoles per 10 minutes) was confirmed as lower than acid secretion rates previously reported in conscious rats. Exendin increased gastric acid secretion several‐fold above basal secretion rate, with maximal effect at 20‐30 minutes post‐injection. The anesthetized rat is a suitable model for assessing acute effects of peptides on stimulation of gastric acid secretion. The low basal acid secretion provides a substantial margin to successfully observe stimulation of acid secretion above an unstimulated baseline for at least 90 minutes. This model also allows simultaneous evaluation of hemodynamics and blood samples for pharmacokinetics and biomarker analysis.

Sa1725 FFA2 Activation Suppresses Basal and Stimulated Gastric Acid Secretion via 5-HT3 Receptor Activation in Rats

Sa1725 FFA2 Activation Suppresses Basal and Stimulated Gastric Acid Secretion via 5-HT3 Receptor Activation in Rats

Перспектива застосування агоністів PPARγ меланіну та піоглітазону при тривалій гіпоацидності шлунка

It was investigated the effects of agonists of nuclear receptors peroxisome proliferator-activated receptors gamma (PPARγ) melanin and pioglitazone оn the secretory function of the stomach in rats under long hypoacidity of gastric juices caused bу the introduction of Н+-К+- ATPase blocker omeprazole during 28 days. As а result of studies it was found that administration of omeprazole for 28 days leads to increase of hydrochloric acid secretion of stomach, resulting in the development of hypergastrinemia. Activation of PPARy Bу pioglitazone and melanin in the conditions of the development of experimental hypergastrinemia prevents the hypertrophy of the gastric mucosa and decreases debit of the basal gastric acid secretion in rats.

The gastric mucosa 25 years after proximal gastric vagotomy

Objective. Vagotomy causes inhibition of basal and post-prandial acid secretion in humans, but the knowledge about the trophic effect of the vagal nerves is limited. Vagotomy is known to induce hypergastrinemia and we aimed to study the long-term effects of proximal gastric vagotomy (PGV) on the oxyntic mucosa and the enterochromaffin-like (ECL) cell density in particular. Material and methods. Eleven patients operated with PGV because of duodenal ulcer and age- and sex-matched controls were examined 26 to 29 years postoperatively by gastroscopy with biopsies from the antrum and oxyntic mucosa. Neuroendocrine cell volume densities were calculated after immunohistochemical labeling of gastrin, the general neuroendocrine cell marker chromogranin A (CgA) and the ECL cell marker vesicular monoamine transporter 2 (VMAT2). Gastritis was graded and Helicobacter pylori (H. pylori) status was determined by polymerase chain reaction of gastric biopsies. Fasting serum gastrin and CgA were measured. Results. Serum gastrin was higher in the PGV group compared to controls (median 21.0 [interquartile range (IQR) = 22.0] pmol/L vs 13.0 [IQR = 4.0] pmol/L, p = 0.04). However, there was neither a significant difference in serum CgA or in CgA (neuroendocrine) nor VMAT2 (ECL cell) immunoreactive cell volume density in the oxyntic mucosa. There was significantly more inflammation and atrophy in H. pylori-positive patients, but PGV did not influence the grade of gastritis. Conclusion. Despite higher serum gastrin concentrations, patients operated with PGV did not have higher ECL cell mass or serum CgA. Vagotomy may prevent the development of ECL cell hyperplasia caused by a moderate hypergastrinemia.

Gastric antiulcer, antisecretory and cytoprotective properties of celery (Apium graveolens) in rats

Celery seed is generally regarded as safe for human consumption as a spice, natural seasoning and plant extract/essential oil. The present study was carried out to assess the possible anti-gastric ulcer, cytoprotective and antisecretory properties of ethanolic extract of Apium graveolens in rats in order to substantiate the traditional Unani, Arab and Ayurvedic medicine practitioners' claim of its use in stomach disorders. 500 grams of the shade dried aerial parts of celery was coarse powdered and macerated in 3 liters of 96% ethanol for 72 hours using percolation method. Wistar albino rats were used. The stomach was removed, opened along the greater curvature, washed with saline and the inner surface was examined with a 6.4 × binocular magnifier. Celery extract was administered orally (250 and 500 mg/kg body weight) 30 minutes before indomethacin. The rats were killed 6 hours after indomethacin administration. Gastric antisecretory activity was evaluated in rats. The animals were deprived of food for 36h with access to water ad libitum. Under light ether anaesthesia, a small midline abdominal incision was made and the pylorus ligated. The wound was closed using sterile suture. The plant extract or normal saline was administered intraperitoneally immediately after pylorus ligation. Six hours after pylorus ligation the animals were sacrificed by cervical displacement. The stomachs were removed from both groups (treated and control), the gastric contents collected and centrifuged. The volume of the supernatant was measured and titratable acidity of liquid gastric content was recorded and calculated. Celery extract produced a dose-dependent significant protection against the ulcerogenic effect induced by indomethacin. In the ethanol and strong alkali-induced ulcer protocol, it was observed that the treatment with ethanolic extract of celery (250 and 500 mg/kg) significantly reduced the lesion index. A highly significant reduction of ulceration in rats' stomach and intraluminal bleeding was recorded after celery extract pretreatment at the dose of 500 mg/kg orally. In the gastric secretion determination model, using ligated pylorus for 6h, the treatment with celery extract (250 and 500 mg/kg i.p.), reduced the volume of basal gastric secretion, titratable acidity and ulceration significantly in comparison with control group. The results show that ethanol extract of Celery displays gastroprotective activity, as demonstrated by its significant inhibition of the formation of ulcers induced by different experimental models, and its ability to decrease basal gastric acid secretion. This gastric antiulcer capacity of celery extract could be related to its antioxidant properties, resulting in reduction of the lipid peroxidation and elevation of the NP-SH contents, besides, improving mucus coat of the stomach. Therefore, we suggest that due to its antioxidative effects, it may be useful in the prevention of gastric disorders.

Protective effect of omeprazole on gastric mucosal of cirrhotic portal hypertension rats

ObjectiveTo observe the protective effect of omeprazole on gastric mucosal of cirrhotic portal hypertension rats. MethodsAll rats were randomly divided into normal control group, cirrhosis and treatment group. Thioacetamide was used to establish rat model of cirrhotic portal hypertension. The necrotic tissue of gastric mucosa ulcer focus, degree of neutrophils infiltration at the ulcer margin, portal pressure, portal venous flow, abdominal aortic pressure, abdominal aortic blood flow at front end, gastric mucosal blood flow (GMBF), glycoprotein (GP) of gastric mucosa, basal acid secretion, H+back -diffusion, gastric mucosal damage index, NO, prostaglandin E2(PGE2) and tumor necrosis factor-α (TNF-α) were determined respectively, and the pathological changes of gastric mucosa were also observed by microscope. ResultsCompared with cirrhosis group and the control group, the ulcer bottom necrotic material, gastric neutrophil infiltration and UI of the treatment group were all decreased significantly (P<0.01), GMBF value, GP values, serum NO, PGE2, TNF-α were all significantly increased. ConclusionsOmeprazole has an important protective effect on gastric mucosal and it can increase gastric mucosal blood flow and related to many factors.