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Marine Drugs Dec 2022Peptic ulcer is a widespread disease, with a lifetime frequency of 5−10% among the general population and an annual incidence of 0.1−0.3%. Ovothiol A is naturally...
Peptic ulcer is a widespread disease, with a lifetime frequency of 5−10% among the general population and an annual incidence of 0.1−0.3%. Ovothiol A is naturally produced from sea urchin eggs with special antioxidant activity. Gastric ulcers were induced in rats by a single ethanol dose (5 mL/kg). The rats were divided into control, ulcer, and ulcer with 250 and 500 mg/kg ovothiol A doses. Molecular docking studies were used to examine the interactions between ovothiol A and the H+/K+ ATPase active site residues. Ovothiol A led to a significant decline (p < 0.05) in gastric juice volume, ulcer index, MDA, IL-6, and cytochrome c, while levels of gastric juice pH, GSH, CAT, GST, SOD, and NO increased. Histopathological investigation of stomach sections revealed architecture preservation of the gastric mucosa after ovothiol A administration. The anti-ulcerogenic activity of ovothiol A includes scavenging free radicals, inhibition of inflammation, regulation of apoptosis, and stabilization of fibroblast growth factors to promote gastric ulcers healing.
Topics: Humans; Rats; Animals; Rats, Wistar; Stomach Ulcer; Ethanol; Molecular Docking Simulation; Anti-Ulcer Agents; Superoxide Dismutase; Gastric Mucosa; Plant Extracts
PubMed: 36662198
DOI: 10.3390/md21010025 -
The Turkish Journal of Gastroenterology... Sep 2022Previous studies found metformin as an effective agent to suppress oxidative stress, inflammation, and apoptosis in various inflammatory diseases. The present study...
BACKGROUND
Previous studies found metformin as an effective agent to suppress oxidative stress, inflammation, and apoptosis in various inflammatory diseases. The present study investigated the effect of metformin against 2 experimental gastric injury models in rats, using macroscopical, histopathological, biochemical, and immunostaining studies.
METHODS
After 24 hours of fasting, male Sprague-Dawley rats (280-400 g) (n = 8 per group) received indomethacin (80 mg/kg; indo ulcer group) or absolute ethanol (5 mL/kg; ethanol ulcer group) or vehicle orally by gavage. Metformin (500 mg/kg) was given orally for 3 days prior to indomethacin or ethanol challenge. Ranitidine (50 mg/kg) was given orally for 3 days before indomethacin or ethanol administration as a positive control. On day 3, the animals were euthanized 6 hours after indo or 1 hour after ethanol challenge. Gastric samples were used for macroscopic scoring, histopathological examinations, and biochemical assays. Trunk blood was collected for the assessment of interleukin-1β level.
RESULTS
In both ethanol ulcer and indo ulcer groups, metformin decreased the extent of gastric lesions macroscopically and microscopically, improved the high chemiluminescence levels, and the percentage of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells compared with untreated ulcer groups. Gastric blood flow analysis revealed significant increases in both metformin-treated ulcer groups compared to untreated ulcer groups.
CONCLUSION
The findings of the present work demonstrated the gastroprotective effect of metformin against the development of gastric mucosal lesions induced by ethanol and indomethacin in non-diabetic, normoglycemic rats via its antioxidant and anti-apoptotic properties and partly from its ability to restore blood flow.
Topics: Animals; Anti-Ulcer Agents; Antioxidants; DNA Nucleotidylexotransferase; Ethanol; Gastric Mucosa; Indomethacin; Interleukin-1beta; Male; Metformin; Ranitidine; Rats; Rats, Sprague-Dawley; Stomach Ulcer
PubMed: 35946894
DOI: 10.5152/tjg.2022.21195 -
Nature Communications Jul 2019Gastric acid suppression promotes allergy in mechanistic animal experiments and observational human studies, but whether gastric acid inhibitors increase allergy...
Gastric acid suppression promotes allergy in mechanistic animal experiments and observational human studies, but whether gastric acid inhibitors increase allergy incidence at a population level remains uncharacterized. Here we aim to assess the use of anti-allergic medication following prescription of gastric acid inhibitors. We analyze data from health insurance records covering 97% of Austrian population between 2009 and 2013 on prescriptions of gastric acid inhibitors, anti-allergic drugs, or other commonly prescribed (lipid-modifying and antihypertensive) drugs as controls. Here we show that rate ratios for anti-allergic following gastric acid-inhibiting drug prescriptions are 1.96 (95%CI:1.95-1.97) and 3.07 (95%-CI:2.89-3.27) in an overall and regional Austrian dataset. These findings are more prominent in women and occur for all assessed gastric acid-inhibiting substances. Rate ratios increase from 1.47 (95%CI:1.45-1.49) in subjects <20 years, to 5.20 (95%-CI:5.15-5.25) in > 60 year olds. We report an epidemiologic relationship between gastric acid-suppression and development of allergic symptoms.
Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Austria; Female; Gastric Acid; Humans; Hypersensitivity; Immune System; Incidence; Male; Medical Records; Middle Aged; Proton Pump Inhibitors; Young Adult
PubMed: 31363098
DOI: 10.1038/s41467-019-10914-6 -
Biomedicine & Pharmacotherapy =... Sep 2022Calanthe fimbriata Franch. is a Tujia ethnic herb, which has traditionally been used to treat gastric ulcers, chronic hepatitis, etc. We explored the chemical...
Calanthe fimbriata Franch. is a Tujia ethnic herb, which has traditionally been used to treat gastric ulcers, chronic hepatitis, etc. We explored the chemical constitutes, gastroprotective effects, and the active fraction of C. fimbriata, as well as elucidating the underlying mechanisms. Firstly, four in vitro antioxidant tests were applied to determine the oxidation resistance of C. fimbriata methanol extract and its fractions. The gastroprotective effects were evaluated in ethanol-induced gastric ulcer rats, gastric histopathology was visualized by H&E staining, and the acidity of gastric juice was measured by titrating with NaOH solution. The contents of malondialdehyde, catalase, superoxide dismutase, gastrin, and the activity of HK-ATPase were estimated using commercial kits. EtOAc fraction of C. fimbriata methanol extract (CfEF) exhibited significant gastroprotective effects by ameliorating stomach pathological changes and elevating the pH value of gastric juice. It also manifested remarkable antioxidant activities in vitro and in vivo. Using various chromatographic methods and spectroscopic techniques, 22 compounds were isolated and characterized from CfEF, in which alkaloids were the predominant components. All of these substances were derived from C. fimbriata for the first time. The results indicated that CfEF is a promising source of gastroprotective agents. The antioxidant activity of this herb, as well as prevention of gastrin secretion and inhibition of H+K+ -ATPase, was found to be the underlying mechanism of action.
Topics: Animals; Anti-Ulcer Agents; Antioxidants; Gastric Mucosa; Gastrins; H(+)-K(+)-Exchanging ATPase; Methanol; Orchidaceae; Plant Extracts; Rats; Stomach Ulcer
PubMed: 36076494
DOI: 10.1016/j.biopha.2022.113468 -
Molecules (Basel, Switzerland) Sep 2020has been commonly used as a multi-use medicinal plant in folk medicine worldwide. The objectives of our study were to determine the different metabolites in the Rottb....
has been commonly used as a multi-use medicinal plant in folk medicine worldwide. The objectives of our study were to determine the different metabolites in the Rottb. methanol extract, and to assess its in vivo gastroprotective effect in ethanol-induced gastric ulcer model in rats. Serum levels of galactin-3 and TNF- were employed as biochemical markers. To pinpoint for active agents, comprehensive metabolites profiling of extract via UPLC-qTOF-MS/MS was employed. A total of 77 chromatographic peaks were detected, of which 70 were annotated. The detected metabolites were categorized into phenolic acids and their derivatives, flavonoids, stilbenes, aurones, quinones, terpenes, and steroids. Rats were divided into six groups; healthy control, ulcer control, standard drug group, and 25, 50, 100 mg/kg of treated rats. Pre-treatment with alcohol extract significantly reduced galactin-3, and TNF- in ethanol-induced ulcer model at 25, 50, and 100 mg/kg. Further histopathological and histochemical studies revealed moderate erosion of superficial epithelium, few infiltrated inflammatory cells, and depletion of gastric tissue glycoprotein in the ulcer group. Treatment with the extract protected the gastric epithelial cells in a dose-dependent manner. It could be concluded that extract provides significant gastroprotective activity in ethanol-induced gastric ulcer and ought to be included in nutraceuticals in the future for ulcer treatment.
Topics: Administration, Oral; Animals; Anti-Ulcer Agents; Chromatography, High Pressure Liquid; Cyperus; Ethanol; Female; Galectin 3; Gastric Mucosa; Phytochemicals; Plant Components, Aerial; Plant Extracts; Ranitidine; Rats; Rats, Wistar; Stomach Ulcer; Tandem Mass Spectrometry; Tumor Necrosis Factor-alpha
PubMed: 32942704
DOI: 10.3390/molecules25184234 -
Molecules (Basel, Switzerland) Feb 2022L. essential oil (EO), mainly composed of myrtenyl acetate (30.6%), linalool (14.9%), α-pinene (11.10%) and 1,8-cineole or eucalyptol (9.9%), was microencapsulated...
L. essential oil (EO), mainly composed of myrtenyl acetate (30.6%), linalool (14.9%), α-pinene (11.10%) and 1,8-cineole or eucalyptol (9.9%), was microencapsulated with maltodextrin by emulsification and spray-drying, reaching a yield and efficiency of 43.7 and 48.7%, respectively. The microencapsulated myrtle EO (MMEO) was then evaluated regarding its gastroprotective activity in a model of ethanol/HCl-induced acute gastric ulcer in Wistar rats. Pretreatment with MMEO induced a remarkable inhibition of gastric lesions and acidity, correlated to high healing and protection percentages. Moreover, it exerted a potent anti-inflammatory effect on the gastric mucosa, counteracting EtOH-induced gastric lipoperoxidation and preventing the depletion of the antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Taken together, the gastroprotective action of encapsulated MMEO may be multi-factorial, and ascribable, at least in parts, to its anti-inflammatory and antioxidant properties.
Topics: Animals; Anti-Ulcer Agents; Ethanol; Gastric Mucosa; Myrtus; Oils, Volatile; Plant Extracts; Rats; Rats, Wistar; Stomach Ulcer
PubMed: 35268666
DOI: 10.3390/molecules27051566 -
The British Journal of General Practice... Dec 2022Proton pump inhibitor (PPI) indications are limited to gastrointestinal disorders and ulcer prophylaxis. However, PPIs are among the most frequently prescribed drugs. (Observational Study)
Observational Study
BACKGROUND
Proton pump inhibitor (PPI) indications are limited to gastrointestinal disorders and ulcer prophylaxis. However, PPIs are among the most frequently prescribed drugs.
AIM
To evaluate the appropriateness of PPI prescriptions and identify predictive factors for inappropriate PPI use.
DESIGN AND SETTING
Observational study using a Dutch primary care database with all new PPI prescriptions between 2016 and 2018.
METHOD
Individual patient data and details on PPI use were collected. The appropriateness of initiation and continuation of PPI prescriptions was evaluated using the applicable guidelines.
RESULTS
In total, 148 926 patients (aged ≥18 years) from 27 general practices were evaluated. A total of 23 601 (16%) patients started PPI therapy (mean age 57 [SD 17] years, 59% female). Valid PPI indications at initiation were seen in 10 466 PPI users (44%). Predictors for inappropriately initiated PPI use were older age (odds ratio [OR] 1.03, 95% confidence interval [CI] = 1.03 to 1.03), and use of non-selective non-steroidal anti-inflammatory drugs (OR 5.15, 95% CI = 4.70 to 5.65), adenosine diphosphate receptor inhibitors (OR 5.07, 95% CI = 3.46 to 7.41), COX-2 inhibitors (also known as coxibs) (OR 3.93, 95% CI = 2.92 to 5.28), and low-dose aspirin (OR 3.83, 95% CI = 3.07 to 4.77). Despite an initial valid indication, PPI use was inaccurately continued in 32% of patients on short-course therapy for dyspepsia and in 11% of patients on ulcer prophylaxis.
CONCLUSION
More than half of PPI users in primary care were found to have an inappropriate indication, with unnecessary ulcer prophylaxis related to drug use being one of the leading causes. Future initiatives to reduce PPI use for unnecessary ulcer prophylaxis and timely deprescription if PPI is no longer indicated, are needed.
Topics: Humans; Female; Adolescent; Adult; Middle Aged; Male; Proton Pump Inhibitors; Ulcer; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Primary Health Care
PubMed: 36127156
DOI: 10.3399/BJGP.2022.0178 -
The Cochrane Database of Systematic... Jun 2018Upper gastrointestinal (GI) bleeding due to stress ulcers contributes to increased morbidity and mortality in people admitted to intensive care units (ICUs). Stress... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Upper gastrointestinal (GI) bleeding due to stress ulcers contributes to increased morbidity and mortality in people admitted to intensive care units (ICUs). Stress ulceration refers to GI mucosal injury related to the stress of being critically ill. ICU patients with major bleeding as a result of stress ulceration might have mortality rates approaching 48.5% to 65%. However, the incidence of stress-induced GI bleeding in ICUs has decreased, and not all critically ill patients need prophylaxis. Stress ulcer prophylaxis can result in adverse events such as ventilator-associated pneumonia; therefore, it is necessary to evaluate strategies that safely decrease the incidence of GI bleeding.
OBJECTIVES
To assess the effect and risk-benefit profile of interventions for preventing upper GI bleeding in people admitted to ICUs.
SEARCH METHODS
We searched the following databases up to 23 August 2017, using relevant search terms: MEDLINE; Embase; the Cochrane Central Register of Controlled Trials; Latin American Caribbean Health Sciences Literature; and the Cochrane Upper Gastrointestinal and Pancreatic Disease Group Specialised Register, as published in the Cochrane Library (2017, Issue 8). We searched the reference lists of all included studies and those from relevant systematic reviews and meta-analyses to identify additional studies. We also searched the World Health Organization International Clinical Trials Registry Platform search portal and contacted individual researchers working in this field, as well as organisations and pharmaceutical companies, to identify unpublished and ongoing studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs with participants of any age and gender admitted to ICUs for longer than 48 hours. We excluded studies in which participants were admitted to ICUs primarily for the management of GI bleeding and studies that compared different doses, routes, and regimens of one drug in the same class because we were not interested in intraclass effects of drugs.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as recommended by Cochrane.
MAIN RESULTS
We identified 2292 unique records.We included 129 records reporting on 121 studies, including 12 ongoing studies and two studies awaiting classification.We judged the overall risk of bias of two studies as low. Selection bias was the most relevant risk of bias domain across the included studies, with 78 studies not clearly reporting the method used for random sequence generation. Reporting bias was the domain with least risk of bias, with 12 studies not reporting all outcomes that researchers intended to investigate.Any intervention versus placebo or no prophylaxisIn comparison with placebo, any intervention seems to have a beneficial effect on the occurrence of upper GI bleeding (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.39 to 0.57; moderate certainty of evidence). The use of any intervention reduced the risk of upper GI bleeding by 10% (95% CI -12.0% to -7%). The effect estimate of any intervention versus placebo or no prophylaxis with respect to the occurrence of nosocomial pneumonia, all-cause mortality in the ICU, duration of ICU stay, duration of intubation (all with low certainty of evidence), the number of participants requiring blood transfusions (moderate certainty of evidence), and the units of blood transfused was consistent with benefits and harms. None of the included studies explicitly reported on serious adverse events.Individual interventions versus placebo or no prophylaxisIn comparison with placebo or no prophylaxis, antacids, H2 receptor antagonists, and sucralfate were effective in preventing upper GI bleeding in ICU patients. Researchers found that with H2 receptor antagonists compared with placebo or no prophylaxis, 11% less developed upper GI bleeding (95% CI -0.16 to -0.06; RR 0.50, 95% CI 0.36 to 0.70; 24 studies; 2149 participants; moderate certainty of evidence). Of ICU patients taking antacids versus placebo or no prophylaxis, 9% less developed upper GI bleeding (95% CI -0.17 to -0.00; RR 0.49, 95% CI 0.25 to 0.99; eight studies; 774 participants; low certainty of evidence). Among ICU patients taking sucralfate versus placebo or no prophylaxis, 5% less had upper GI bleeding (95% CI -0.10 to -0.01; RR 0.53, 95% CI 0.32 to 0.88; seven studies; 598 participants; moderate certainty of evidence). The remaining interventions including proton pump inhibitors did not show a significant effect in preventing upper GI bleeding in ICU patients when compared with placebo or no prophylaxis.Regarding the occurrence of nosocomial pneumonia, the effects of H2 receptor antagonists (RR 1.12, 95% CI 0.85 to 1.48; eight studies; 945 participants; low certainty of evidence) and of sucralfate (RR 1.33, 95% CI 0.86 to 2.04; four studies; 450 participants; low certainty of evidence) were consistent with benefits and harms when compared with placebo or no prophylaxis. None of the studies comparing antacids versus placebo or no prophylaxis provided data regarding nosocomial pneumonia.H2 receptor antagonists versus proton pump inhibitorsH2 receptor antagonists and proton pump inhibitors are most commonly used in practice to prevent upper GI bleeding in ICU patients. Proton pump inhibitors significantly more often prevented upper GI bleeding in ICU patients compared with H2 receptor antagonists (RR 2.90, 95% CI 1.83 to 4.58; 18 studies; 1636 participants; low certainty of evidence). When taking H2 receptor antagonists, 4.8% more patients might experience upper GI bleeding (95% CI 2.1% to 9%). Nosocomial pneumonia occurred in similar proportions of participants taking H2 receptor antagonists and participants taking proton pump inhibitors (RR 1.02, 95% CI 0.77 to 1.35; 10 studies; 1256 participants; low certainty of evidence).
AUTHORS' CONCLUSIONS
This review shows that antacids, sucralfate, and H2 receptor antagonists might be more effective in preventing upper GI bleeding in ICU patients compared with placebo or no prophylaxis. The effect estimates of any treatment versus no prophylaxis on nosocomial pneumonia were consistent with benefits and harms. Evidence of low certainty suggests that proton pump inhibitors might be more effective than H2 receptor antagonists. Therefore, patient-relevant benefits and especially harms of H2 receptor antagonists compared with proton pump inhibitors need to be assessed by larger, high-quality RCTs to confirm the results of previously conducted, smaller, and older studies.
Topics: Anti-Ulcer Agents; Blood Transfusion; Cause of Death; Histamine H2 Antagonists; Humans; Intensive Care Units; Length of Stay; Peptic Ulcer Hemorrhage; Pneumonia; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Selection Bias; Stress, Psychological; Sucralfate
PubMed: 29862492
DOI: 10.1002/14651858.CD008687.pub2 -
Molecules (Basel, Switzerland) Nov 2020The carrot plant ) and its components are traditionally reported for the management of gastric ulcers. This study was performed to evaluate the role of carrot when...
The carrot plant ) and its components are traditionally reported for the management of gastric ulcers. This study was performed to evaluate the role of carrot when administered concurrently with a conventional antiulcer treatment, pantoprazole, in alleviating gastric and duodenal ulcers in female experimental animals. The study involved standard animal models to determine the ulcer preventive effect using pylorus ligation, ethanol, and stress induced acute gastric ulcer models and duodenal ulcer models involving cysteamine. Acetic acid-induced chronic gastric ulcer and indomethacin-induced gastric ulcer models were used to evaluate the ulcer healing effect. Carrot fruit (500 mg/kg) and its co-administration with pantoprazole produced significant protection in an ethanol- and stress-induced acute gastric ulcer and cysteamine-induced duodenal ulcer. The healing of the acetic acid-induced chronic gastric ulcer was also augmented with this combination. Both total proteins and mucin contents were significantly increased in indomethacin-induced gastric ulcers. Similarly, in pylorus ligation, the pepsin content of gastric juice, total acidity, and free acidity were reduced. Overall, both ulcer preventive effects and ulcer healing properties of the pantoprazole were significantly enhanced in animals who received the co-administration of carrot fruit (500 mg/kg).
Topics: Acetic Acid; Animals; Anti-Ulcer Agents; Antioxidants; Biphenyl Compounds; Cysteamine; Daucus carota; Drug Synergism; Ethanol; Female; Free Radical Scavengers; Indomethacin; Inhibitory Concentration 50; Pantoprazole; Pepsin A; Picrates; Plant Preparations; Pylorus; Rats; Rats, Wistar
PubMed: 33202703
DOI: 10.3390/molecules25225287 -
Biomedicine & Pharmacotherapy =... Sep 2020Gastrointestinal diseases are very common problems; available treatments are very limited and come with a range of side effects. Coumarins are an extensive class of...
Gastrointestinal diseases are very common problems; available treatments are very limited and come with a range of side effects. Coumarins are an extensive class of phenolic compounds that can be found in plants, fungi and bacteria. The 7-hydroxycoumarin, also known as umbelliferone (UMB), is a compound that comes from coumarin and has been showing biological activities in other studies. As of this scenario, the present study was designed to evaluate the acute oral toxicity, mutagenic, antidiarrheal, anti-bacterial, and antiulcerogenic effects, and antioxidant capacity of UMB. An investigation was conducted through the hippocratic screening method and through histopathological analysis in animals to evaluate the effects of acute oral administration of a dose of 50, 100 and 200 mg/kg of UMB. A micronucleus test on peripheral blood of Swiss mice, which were orally treated with three doses (50, 100 and 200 mg/kg), was conducted to evaluate mutagenic activities. The antiulcerogenic activity was accomplished through the ethanol-induced damage method. Antidiarrheal activities were tested for inducing diarrhea with castor oil and evaluating intestinal transit duration; additionally, the antimicrobial effect against some enteropathogenic bacteria was analyzed. Finally, the antioxidant capability was determined by the capacity of the UMB sample to kidnap the stable radical 2,2-diphenyl-1-picrylhydrazyl. Of the evaluated doses, signs of toxicity after acute administration of the compound were not observed. UMB presented antiulcerogenic activity (100 and 200 mg/kg), which was explained because of its antioxidant capacity. A gastro protective effect was similar to the positive control, and the UMB was able to significantly reduce intestinal transit, and also diarrheal symptoms. Furthermore, UMB had an anti-bacterial effect with minimum inhibitory concentration fluctuating between 62.5 and 1000 μg/mL. Based on these findings, we can suggest that UMB has important biological activities in vivo and in vitro and is not toxic under the evaluated circumstances, which demonstrates its large potential for pharmacological use.
Topics: Animals; Anti-Bacterial Agents; Anti-Ulcer Agents; Antidiarrheals; Bacteria; Castor Oil; Defecation; Diarrhea; Disease Models, Animal; Ethanol; Gastrointestinal Motility; Male; Mice; Stomach; Stomach Ulcer; Umbelliferones
PubMed: 32768935
DOI: 10.1016/j.biopha.2020.110432