NSAID-induced Ulcers Research Articles

Gardenia jasminoides fruit extract alleviates non-steroidal anti-inflammatory drug–induced gastropathy in rats

BackgroundNSAID-induced gastropathy is a health burden that requires effective intervention. Among various prevention options, Gardenia jasminoides fruit extract (GJE) has demonstrated gastroprotective effects through anti-inflammatory pathways with a wide safety margin. However, the detailed molecular mechanisms of GJE regarding mucoprotective and anti-inflammatory effects remained to be explored. Therefore, we investigated the effects of GJE on NSAID-induced gastric injury in rats, focusing on the expression of the protective factors: prostaglandin E2 (PGE2) and mucin 5AC (MUC5AC), and the aggravating factors: inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB).MethodsTwenty-four male Sprague–Dawley rats were assigned to three experimental groups (n = 8/group): the control group, the NSAIDs group receiving indomethacin to induce gastric ulcers, and the NSAIDs with GJE pretreatment (NSAIDs + GJE) group. After a two-day experimental period, the stomachs were collected for histopathological examination, immunohistochemical staining, and protein expression analysis in gastric tissue lysates.ResultsThe NSAIDs group exhibited severe neutrophil infiltration with ulcers upon gastric histopathological examination. Pretreatment with GJE attenuated NSAID-induced gastropathy, as evidenced by reduced neutrophil infiltration and decreased ulceration. Immunohistochemical staining and Western blotting demonstrated reduced expressions of PGE2 and MUC5AC, while the expressions of iNOS and NF-κB were increased following NSAID administration. In comparison to the NSAIDs group, the NSAIDs + GJE group exhibited higher expressions of PGE2 and MUC5AC and lower expressions of iNOS and NF-κB, providing evidence of the gastroprotective effects of GJE.ConclusionsPretreatment with GJE alleviated NSAID-induced gastric ulcers by increasing the expression of PGE2 and MUC5AC and decreasing the expression of iNOS and NF-κB. This study contributes to the understanding of the mechanisms by which GJE attenuates NSAID-induced gastropathy. Further studies are required to validate the effect of GJE in clinical settings.

NSAID-induced Gastric Ulcer Disease: A Deleterious Connection.

Gastric ulcers induced by non-steroidal anti-inflammatory drug (NSAID) usage have become a common public health problem, and several studies have established chronic NSAID usage to be one of the risk factors for the pathogenesis of peptic ulcers in patients. This review includes numerous articles that link NSAID usage with peptic mucosal erosion, especially among patients under anticoagulant therapy or with other risk factors. Risk factors for NSAID-induced peptic ulcers are reviewed, in addition to pathogenesis, clinical signs, symptoms, diagnosis, prevention, and treatments. We also emphasize effective methods for the prevention and management of peptic ulcers among NSAID users. Such methods include the use of selective Cyclo-oxygenase (COX-2) inhibitors as an alternative to aspirin or other Cyclo-oxygenase (COX-1) inhibitors, or using the lowest dosage possible in patients with other comorbidities. We have conducted a thorough review of the literature on diagnostic tests and alternative medication that can be used in the management of NSAID toxicity-induced ulcers.

Continuous co-prescription of rebamipide prevents upper gastrointestinal bleeding in NSAID use for orthopaedic conditions: A nested case-control study using the LIFE Study database.

Rebamipide has been widely co-prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) in Japan for decades. This study aimed to evaluate the effectiveness of rebamipide in preventing upper gastrointestinal bleeding in new users of NSAIDs without risk factors of NSAID-induced ulcers other than age. A nested case-control study was conducted using medical claims data of 1.66 million inhabitants of 17 municipalities participating in Japan's Longevity Improvement & Fair Evidence study. The cohort entry (t0) corresponded to a new user of NSAIDs for osteoarthritis or low back pain. Patients with risk factors of NSAID-induced ulcers other than age were excluded. Cases were defined as patients who underwent gastroscopy for upper gastrointestinal bleeding (occurrence date was defined as index date). A maximum of 10 controls were selected from non-cases at the index date of each case by matching sex, age, follow-up time, and type and dosage of NSAIDs. Exposure to rebamipide was defined as prescription status from t0 to index date: Non-user (rebamipide was not co-prescribed during the follow-up period), Continuous-user (rebamipide was co-prescribed from t0 with the same number of tablets as NSAIDs), and Irregular-user (neither Non-user nor Continuous-user). Conditional logistic regression analysis was conducted to estimate each category's odds ratio compared to non-users. Of 67,561 individuals who met the inclusion criteria, 215 cases and 1,516 controls were selected. Compared with that of Non-users, the odds ratios and 95% confidence interval were 0.65 (0.44-0.96) for Continuous-users and 2.57 (1.73-3.81) for Irregular-users. Continuous co-prescription of rebamipide significantly reduced the risk of upper gastrointestinal bleeding in an Asian cohort of new users of NSAIDs with osteoarthritis or low back pain without risk factors other than age.

Rapamycin and Starvation Mitigate Indomethacin-Induced Intestinal Damage through Preservation of Lysosomal Vacuolar ATPase Integrity.

Nonsteroidal anti-inflammatory drugs (NSAIDs) possess anti-inflammatory, antipyretic, and analgesic properties and are among the most commonly used drugs. Although the cause of NSAID-induced gastric ulcers is well understood, the mechanism behind small intestinal ulcers remains elusive. In this study, we examined the mechanism through which indomethacin (IM), a prominent NSAID, induces small intestinal ulcers, both in vitro and in vivo. In IEC6 cells, a small intestinal epithelial cell line, IM treatment elevated levels of LC3-II and p62. These expression levels remained unaltered after treatment with chloroquine or bafilomycin, which are vacuolar ATPase (V-ATPase) inhibitors. IM treatment reduced the activity of cathepsin B, a lysosomal protein hydrolytic enzyme, and increased the lysosomal pH. There was a notable increase in subcellular colocalization of LC3 with Lamp2, a lysosome marker, post IM treatment. The increased lysosomal pH and decreased cathepsin B activity were reversed by pretreatment with rapamycin (Rapa) or glucose starvation, both of which stabilize V-ATPase assembly. To validate the in vitro findings in vivo, we established an IM-induced small intestine ulcer mouse model. In this model, we observed multiple ulcerations and heightened inflammation following IM administration. However, pretreatment with Rapa or fasting, which stabilize V-ATPase assembly, mitigated the IM-induced small intestinal ulcers in mice. Coimmunoprecipitation studies demonstrated that IM binds to V-ATPase in vitro and in vivo. These findings suggest that IM induces small intestinal injury through lysosomal dysfunction, likely due to the disassembly of lysosomal V-ATPase caused by direct binding. Moreover, Rapa or starvation can prevent this injury by stabilizing the assembly. SIGNIFICANCE STATEMENT: This study elucidates the largely unknown mechanisms behind small intestinal ulceration induced by indomethacin and reveals the involvement of lysosomal dysfunction via vacuolar ATPase disassembly. The significance lies in identifying potential preventative interventions, such as rapamycin treatment or glucose starvation, offering pivotal insights that extend beyond nonsteroidal anti-inflammatory drugs-induced ulcers to broader gastrointestinal pathologies and treatments, thereby providing a foundation for novel therapeutic strategies aimed at a wide array of gastrointestinal disorders.

Recent Advances in Molecular Pathways and Therapeutic Implications for Peptic Ulcer Management: A Comprehensive Review.

Peptic ulcers, recognized for their erosive impact on the gastrointestinal mucosa, present a considerable challenge in gastroenterology. Epidemiological insights underscore the global prevalence of peptic ulcers, affecting 5-10+% of individuals, with a yearly incidence of 0.3 to 1.9 cases per thousand. Recent decades have witnessed a decline in complications, attributed to improved diagnostics and therapeutic advancements. The review deepens into H. pylori-associated and NSAID-induced ulcers, emphasizing their distinct prevalence in developing and industrialized nations, respectively. Despite advancements, managing peptic ulcers remains challenging, notably in H. pylori-infected individuals facing recurrence and the rise of antibiotic resistance. The pathophysiology unravels the delicate balance between protective and destructive factors, including the intricate molecular mechanisms involving inflammatory mediators such as TNF-α, ILs, and prostaglandins. Genetic and ethnic factors, rare contributors, and recent molecular insights further enhance our understanding of peptic ulcer development. Diagnostic approaches are pivotal, with upper gastrointestinal endoscopy standing as the gold standard. Current treatment strategies focus on H. pylori eradication, NSAID discontinuation, and proton pump inhibitors. Surgical options become imperative for refractory cases, emphasizing a comprehensive approach. Advances include tailored H. pylori regimens, the emergence of vonoprazan, and ongoing vaccine development. Challenges persist, primarily in antibiotic resistance, side effects of acid suppressants, and translating natural compounds into standardized therapies. Promising avenues include the potential H. pylori vaccine and the exploration of natural compounds, with monoterpenes showing therapeutic promise. This review serves as a compass, guiding healthcare professionals, researchers, and policymakers through the intricate landscape of peptic ulcer management.

Evaluation of the Anti-ulcer Activity of Curcumin and Linseed Oil in an NSAID-induced Gastric Ulcer Model in Rats

Evaluation of the Anti-ulcer Activity of Curcumin and Linseed Oil in an NSAID-induced Gastric Ulcer Model in Rats

Screening of anti-ulcer activity of Emblica officinalis fruit extract on NSAID-induced peptic ulcer model in albino rats

Background: Peptic ulcer disease (PUD) is a prevalent health concern. Although proton pump inhibitors (PPIs), H2 receptor blockers, prostaglandin analogs, etc., are available as anti-ulcer agents, they have their own limitations. The clinical assessment of these medications revealed adverse effects, relapse frequency, and tolerance development, raising doubts about their effectiveness. Thus, there is a need to search for newer synthetic and herbal formulations that have fewer side effects and improved efficacy. Emblica officinalis (EO) or amla has shown to have antioxidant and antisecretory properties; hence, it was chosen for the study. Aims and Objectives: (1) The aim of this study was to screen the anti-ulcer activity of EO aqueous fruit extract in non-steroidal anti-inflammatory drug-induced peptic ulcer models of albino rats and (2) to compare the anti-ulcer effect of EO aqueous fruit extract with the standard drug omeprazole. Materials and Methods: Four groups comprising six albino rats each were formed. Group 1 (the control) received distilled water, followed by indomethacin 25 mg/kg orally. Group 2 (standard) received omeprazole 10 mg/kg, followed by indomethacin 25 mg/kg. Groups 3 and 4 received the aqueous extract of EO in 250 mg/kg and 500 mg/kg doses, respectively, followed by indomethacin at 25 mg/kg. After 1 h of indomethacin administration, the stomach was examined for ulceration. The severity score was determined to calculate the ulcer index (UI) and percentage inhibition. The results were analyzed statistically using the Mann–Whitney U-test (SPSS software version 22). Results: In the screening model mentioned above, the test agent at dosages of 250 mg/kg and 500 mg/kg body weight resulted in a significant decrease in total severity score, UI, and percentage inhibition as compared to the control group. The comparison of the results of the standard drug omeprazole with those of the test groups was statistically insignificant. Conclusion: The gastroprotective activity of amla (EO) may be due to its antioxidant and antisecretory properties. This study proves the gastroprotective action of EO.

Unravelling the Gastroprotective Potential of Kefir: Exploring Antioxidant Effects in Preventing Gastric Ulcers.

The present study was conducted to evaluate the protective effect of milk kefir against NSAID-induced gastric ulcers. Male Swiss mice were divided into three groups: control (Vehicle; UHT milk at a dose of 0.3 mL/100 g), proton pump inhibitor (PPI; lansoprazole 30 mg/kg), and 4% milk kefir (Kefir; 0.3 mL/100 g). After 14 days of treatment, gastric ulcer was induced by oral administration of indomethacin (40 mg/kg). Reactive oxygen species (ROS), nitric oxide (NO), DNA content, cellular apoptosis, IL-10 and TNF-α levels, and myeloperoxidase (MPO) enzyme activity were determined. The interaction networks between NADPH oxidase 2 and kefir peptides 1-35 were determined using the Residue Interaction Network Generator (RING) webserver. Pretreatment with kefir for 14 days prevented gastric lesions. In addition, kefir administration reduced ROS production, DNA fragmentation, apoptosis, and TNF-α systemic levels. Simultaneously, kefir increased NO bioavailability in gastric cells and IL-10 systemic levels. A total of 35 kefir peptides showed affinity with NADPH oxidase 2. These findings suggest that the gastroprotective effect of kefir is due to its antioxidant and anti-inflammatory properties. Kefir could be a promising natural therapy for gastric ulcers, opening new perspectives for future research.

Nimesulide: A double-edged sword must be banned

Dear Editor, My purpose in writing this letter is to draw your attention to a very susceptible situation of possible adverse reactions like hepatotoxicity caused by Nimesulide. It is being prescribed as an over-the-counter drug and is available even online for home delivery without any prescription in Pakistan. Nimesulide is an atypical selective COX-2 inhibitor that is similar in anti-inflammatory effects as compared to other classical NSAIDs and selective COX-2 (celecoxib & rofecoxib) inhibitors but different as it has a protective effect on NSAID-induced ulcers as compared to other more selective COX-2 inhibitors, which do prevent but do not protect NSAID induced ulcers. But, does this only benefit of being gastroprotective justify its use as a relatively common drug with or without a prescription? ---Continue

Gastroparesis Worsens Indomethacin-Induced Gastric Antral Ulcers by Bile Reflux via Activation of 5-HT3 and Dopamine D2 Receptors in Mice.

We examined the contributions of gastric emptying and duodenogastric bile reflux in the formation of gastric antral ulcers induced by NSAIDs in mice. We used the murine re-fed indomethacin (IND) experimental ulcer model. Outcome measures included the appearance of gastric lesions 24h after IND treatment and the assessment of gastric contents and the concentration of bile acids 1.5h after re-feeding. The effects of atropine, dopamine, SR57227 (5-HT3 receptor agonist), apomorphine, ondansetron, haloperidol, and dietary taurocholate and cholestyramine were also examined. IND (10mg/kg, s.c.) induced severe lesions only in the gastric antrum in the re-fed model. The antral lesion index and the amount of food intake during the 2-h refeeding period were positively correlated. Atropine and dopamine delayed gastric emptying, increased bile reflux, and worsened IND-induced antral lesions. SR57227 and apomorphine worsened antral lesions with increased bile reflux. These effects were prevented by the anti-emetic drugs ondansetron and haloperidol, respectively. The anti-emetic drugs markedly decreased the severity of antral lesions and the increase of bile reflux induced by atropine or dopamine without affecting delayed gastric emptying. Antral lesions induced by IND were increased by dietary taurocholate but decreased by the addition of the bile acid sequestrant cholestyramine. These results suggest that gastroparesis induced by atropine or dopamine worsens NSAID-induced gastric antral ulcers by increasing duodenogastric bile reflux via activation of 5-HT3 and dopamine D2 receptors.

Review of the clinical development of fexuprazan for gastroesophageal reflux-related disease.

Proton pump inhibitors (PPIs) are a mainstay treatment for acid peptic disorders such as gastroesophageal reflux disease (GERD). Although PPIs are considered first-line medications for acid suppression, they have notable limitations such as requiring acid-mediated activation, short half-life and duration of action, and metabolic variability. Fexuprazan is a newly developed potassium-competitive acid blocker (P-CAB), which inhibits acid generation and secretion in a competitive and reversible manner. Fexuprazan, like other P-CABs, has significantly different pharmacodynamic and pharmacokinetic properties than PPIs with potential advantages including rapid, robust, and durable acid suppression, lack of CYP2C19 metabolism, independence from food intake, and no requirement for activation into an active form. Completed clinical trials of fexuprazan have demonstrated comparable efficacy to PPIs for the healing of erosive esophagitis and relief of GERD-related esophageal symptoms without concerning safety signals. Ongoing clinical trials are evaluating fexuprazan for the prevention of NSAID-induced peptic ulcer disease, non-erosive GERD, and acute and chronic gastritis, as well as healing efficacy and maintenance of erosive esophagitis (EE). Fexuprazan is approved in South Korea for the treatment of EE and at the time of this writing is being considered for regulatory approval in several other countries. In this article, we summarize and discuss the pharmacology, efficacy, and safety of fexuprazan.

Omeprazole (Risek®) Use in Inpatient and Outpatient Departments: A Post-marketing Surveillance Investigation

Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related gastrointestinal disorders. However, their overuse or inappropriate prescription can lead to adverse effects, increased healthcare costs, and development of antibiotic-resistant infections. Objectives: To ascertain whether the Omeprazole (Risek®)-PPIs prescription patterns by practitioners in the inpatient and outpatient departments of various healthcare facilities in Pakistan are in compliance with the therapeutic indications and to evaluate the safety profile associated with each therapeutic indication. Methods: A cross-sectional multicenter study was conducted for 4 months at various healthcare facilities inpatient and outpatient departments. A total of 1384 patients ≥ 18 years prescribed Omeprazole (Risek®) were enrolled while pregnant or lactating women, patients with chronic diarrhea, those with a history of Omeprazole allergic reaction, and with diagnosed malignancy of the GI tract were excluded. The drug use was determined based on the prescribed frequency, dosage, and duration of therapy with respect to each indication. Results: Of the total, 29.8% were already taking oral PPI or Histamine H2-Receptor Antagonists. The common indication for Omeprazole (Risek®) was Gastroesophageal Reflux Disease (GERD), followed by peptic ulcer. Mostly the drug was infused/injected in 40 mg dosage, once daily and for five days among 76.6% and 41.8%, respectively. Around 13.3% of patients experienced mild adverse events like flatulence, fever, vomiting, abdominal pain, constipation, diarrhea, nausea, rash, etc. Most off-label uses were observed in GERD concerning the duration of therapy (55.9%), prescribed frequency (19.7%), and dosage (5.9%). The Omeprazole (Risek®) treatment was also prescribed for stress ulcer prophylaxis and upper GI bleeding against the treatment protocol for the particular therapeutic indication. The adverse events were most frequent among patients with GERD, followed by NSAID-induced ulcers. Conclusions: This study provides clinical evidence on the Omeprazole (Risek®) use in concordance with the product label, in both inpatient and outpatient departments of Pakistan for various therapeutic indications.

Pumpkin Oil-Based Nanostructured Lipid Carrier System for Antiulcer Effect in NSAID-Induced Gastric Ulcer Model in Rats [Retraction

[This retracts the article DOI: 10.2147/IJN.S247252.].

Development of Prediction Model Using Machine-Learning Algorithms for Nonsteroidal Anti-inflammatory Drug-Induced Gastric Ulcer in Osteoarthritis Patients: Retrospective Cohort Study of a Nationwide South Korean Cohort.

Nonsteroidal anti-inflammatory drugs (NSAID) are currently among the most prescribed medications worldwide to relieve pain and reduce inflammation, especially in patients suffering osteoarthritis (OA). However, NSAIDs are known to have adverse effects on the gastrointestinal system. If a gastric ulcer occurs, planned OA treatment needs to be changed, incurring additional treatment costs and causing discomfort for both patients and clinicians. Therefore, it is necessary to create a gastric ulcer prediction model that can reflect the detailed health status of each individual and to use it when making treatment plans. Using sample cohort data from 2008 to 2013 from the National Health Insurance Service in South Korea, we developed a prediction model for NSAID-induced gastric ulcers using machine-learning algorithms and investigated new risk factors associated with medication and comorbidities. The population of the study consisted of 30,808 patients with OA who were treated with NSAIDs between 2008 and 2013. After a 2-year follow-up, these patients were divided into two groups: without gastric ulcer (n=29,579) and with gastric ulcer (n=1,229). Five machine-learning algorithms were used to develop the prediction model, and a gradient boosting machine (GBM) was selected as the model with the best performance (area under the curve, 0.896; 95% confidence interval, 0.883-0.909). The GBM identified 5 medications (loxoprofen, aceclofenac, talniflumate, meloxicam, and dexibuprofen) and 2 comorbidities (acute upper respiratory tract infection [AURI] and gastroesophageal reflux disease) as important features. AURI did not have a dose-response relationship, so it could not be interpreted as a significant risk factor even though it was initially detected as an important feature and improved the prediction performance. We obtained a prediction model for NSAID-induced gastric ulcers using the GBM method. Since personal prescription period and the severity of comorbidities were considered numerically, individual patients' risk could be well reflected. The prediction model showed high performance and interpretability, so it is meaningful to both clinicians and NSAID users.

Effect of Carrots (Daucus carota L.) on Gastric Histopathology of Piroxicam-Induced Mice as a Peptic Ulcer Prevention

Highlights:1. Carrots (Daucus carota L.) can reduce the side effects of non-steroidal anti-inflammatory drugs (NSAIDs) due to its gastroprotective components.2. Histopathological studies of the gastric inflammation signs showed that carrots can prevent NSAID-induced peptic ulcers. AbstractIntroduction: Non-steroidal anti-inflammatory drugs (NSAIDs) consumption contributes significantly to gastrointestinal morbidity, including peptic ulcers. NSAIDs cause gastric mucosal damage by inhibiting PGE2 and PGI2 secretion, increasing HCl secretion, and also causing local irritation and neutrophil adhesion. Flavonoids and chlorogenic acid are gastroprotective agents found in carrots (Daucus carota L.). Therefore, this study aimed to validate the effect of carrots on gastric histopathology of piroxicam-induced mice.Methods: This was an experimental study using a post-test-only control group design. 35 mice were divided into 5 groups and were allowed to adapt for 1 week. The negative control group received 0.25 mL aqua dest, while the positive control group received 0.104 mg famotidine. Group A, B, and C received carrot extract with each dosage was 200 mg/kgBW, 300 mg/kgBW, and 400 mg/kgBW. The mice were induced 2 hours later with 0.052 mg piroxicam. The treatments lasted 14 days. Each stomach was taken and examined on the 15th day. Afterward, histopathological preparations were made.Results: The results of the histopathological signs of inflammation using the Kruskal-Wallis method showed p = 0.000, indicating that there was an effect of the carrot extract in preventing the inflammation on the gastric histopathology (p < 0.05).Conclusion: In conclusion, this study confirmed that carrot extract is more effective in avoiding peptic ulcers due to NSAID consumption.

Gastroprotective Effects of Aqueous Extract of Hibiscus sabdariffa Calyx on Nonsteroidal Anti-Inflammatory Drug-Induced Gastric Ulcer in Wistar Rats

Background: Gastric ulcer is the most common gastrointestinal disorder associated with high morbidity and significant mortality and has been described as the plaque of the 19th and 20th centuries. The most conventional antiulcer drugs are largely ineffective and associated with disease recurrence, thus identifying natural products with potential antiulcer properties is essential. Objective: The aim of this study was to investigate the potential protective effects of aqueous extract of Hibiscus sabdariffa calyx (AEHSC) against nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcer. Materials and Methods: Thirty male rats weighing 170–230 g were randomized into five groups as: ulcerated control group (distilled water, n = 6), experimental extract groups 1, 2, and 3 (AEHSC 100 mg/kg, 200 mg/kg, and 400 mg/kg, respectively, n = 6 each), and positive control group (ranitidine 20 mg/kg, n = 6); ulcer was induced using oral indomethacin 40 mg/kg, 30 min after all interventions. Rats were sacrificed 5 h after ulcer induction. Blood samples were taken for serum hydroxyproline determination; gastric tissues were also visualized (ulcer index (UI) and percentage of ulcer protection), and later stained and viewed under a microscope. Results: There was a significant (P < 0.05) reduction in UI in treated rats compared with control. The percentage of ulcer protection was also significantly increased (P < 0.05). Histological slides also indicated increased epithelial mucus secretion in stomach tissues of rat treated with AEHSC. Conclusions: AEHSC may be potentially beneficial in protection against the development of NSAID-induced gastric ulcers.

Emblica officinalis Fruit Pulp Extract Protects against Naproxen-Induced Gastric Ulcer in Rats: Anti-inflammatory and Antioxidant Machinery

Background: The use of non-steroidal anti-inflammatory drugs (NSAIDs) is one of the leading causes of peptic ulcers. There is a rising interest and demand for nontoxic, antiulcer remedies derived from medicinal plants to treat NSAID-induced gastric ulcers (GU). Aim: This study is a comparative assessment of the possible gastro-protective role of Emblica officinalis fruit pulp extract (EOFPE) and Omeprazole (Omepra) against Naproxin (Naprox)-induced GU. Methodology: Five groups of rats (8 rats each) represent control, Naprox, Omepra (20 mg/kg), EOFPE (700 mg/kg), and EOFPE + Omepra. Omepra and EOFPE were ingested orally for 17 days. Naprox was ingested orally on day 15 for three consecutive days. Results: Pretreatment with EOFPE and/or Omepra caused significant increases in gastric pH and gastric mucin content. Besides, significant decline in the total gastric acidity and gastric mucosal lesion relative to the Naprox group. Pretreatment with EOFPE and/or Omepra markedly improved the examined gastric pathologic features in Naprox-pretreated groups. Besides, EOFPE and/or Omepra overcome the gastric inflammation and oxidative stress markers induced by Naprox ingestion. Pretreatment with both EOFPE + Omepra leads to the best antiulcer impact and lesion inhibition percent relative to the Naprox groups pretreated with either EOFPE or Omepra alone. Conclusion: EOFPE protected against Naprox-induced GU across anti-inflammatory and antioxidant mechanisms. Keywords: Antioxidant, Anti-inflammatory, Emblica officinalis, Gastric ulcer.

Propolis and Its Gastroprotective Effects on NSAID-Induced Gastric Ulcer Disease: A Systematic Review

Gastric ulcer disease induced by the consumption of NSAIDs is a major public health problem. The therapy used for its treatment causes adverse effects in the patient. Propolis is a natural product that has been used for the treatments of different diseases around the world. Nevertheless, there is little information about the activity of propolis in gastric ulcers caused by treatment with NSAIDs. Therefore, this review evaluates and compares the gastroprotective potential of propolis and its function against NSAID-induced gastric ulcers, for which a systematic search was carried out in the PubMed and ScienceDirect databases. The main criteria were articles that report the gastroprotective activity of propolis against the damage produced by NSAIDs in the gastric mucosa. Gastroprotection was related to the antioxidant, antisecretory, and cytoprotective effects, as well as the phenolic compounds present in the chemical composition of propolis. However, most of the studies used different doses of NSAIDs and propolis and evaluated different parameters. Propolis has proven to be a good alternative for the treatment of gastric ulcer disease. However, future studies should be carried out to identify the compounds responsible for these effects and to determine their potential use in people.

A Convolutional Neural Network Deep Learning Model Trained on CD Ulcers Images Accurately Identifies NSAID Ulcers.

Background and Study Aims: Deep learning (DL) for video capsule endoscopy (VCE) is an emerging research field. It has shown high accuracy for the detection of Crohn's disease (CD) ulcers. Non-steroidal anti-inflammatory drugs (NSAIDS) are commonly used medications. In the small bowel, NSAIDs may cause a variety of gastrointestinal adverse events including NSAID-induced ulcers. These ulcers are the most important differential diagnosis for small bowel ulcers in patients evaluated for suspected CD. We evaluated a DL network that was trained using CD VCE ulcer images and evaluated its performance for NSAID ulcers.Patients and Methods: The network was trained using CD ulcers and normal mucosa from a large image bank created from VCE of diagnosed CD patients. NSAIDs-induced enteropathy images were extracted from the prospective Bifidobacterium breve (BIf95) trial dataset. All images were acquired from studies performed using PillCam SBIII. The area under the receiver operating curve (AUC) was used as a metric. We compared the network's AUC for detecting NSAID ulcers to that of detecting CD ulcers.Results: Overall, the CD training dataset included 17,640 CE images. The NSAIDs testing dataset included 1,605 CE images. The DL network exhibited an AUC of 0.97 (95% CI 0.97–0.98) for identifying images with NSAID mucosal ulcers. The diagnostic accuracy was similar to that obtained for CD related ulcers (AUC 0.94–0.99).Conclusions: A network trained on VCE CD ulcers similarly identified NSAID findings. As deep learning is transforming gastrointestinal endoscopy, this result should be taken into consideration in the future design and analysis of VCE deep learning applications.

Pharmacogenomics of NSAID-Induced Upper Gastrointestinal Toxicity.

Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of drugs which are widely used globally for the treatment of pain and inflammation, and in the case of aspirin, for secondary prevention of cardiovascular disease. Chronic non-steroidal anti-inflammatory drug use is associated with potentially serious upper gastrointestinal adverse drug reactions (ADRs) including peptic ulcer disease and gastrointestinal bleeding. A few clinical and genetic predisposing factors have been identified; however, genetic data are contradictory. Further research is needed to identify clinically relevant genetic and non-genetic markers predisposing to NSAID-induced peptic ulceration.