Gastric Injury Research Articles

The Effect of Desloratadine Upon Ischemia-reperfusion-induced Oxidative and Inflammatory Gastric Injury in Rats

Background: Ischemia-reperfusion (I/R) injury is a pathological process mediated by oxidative stress and inflammation that begins with oxygen deprivation. This study, it was aimed to investigate the protective effect of desloratadine on gastric I/R damage in rats. Methods: Eighteen rats were randomly divided into 3 groups gastric I/R (GIR), gastric I/R + 5 mg/kg oral desloratadine (GIRD) and gastric sham operation (GSG). One hour later desloratadine administration, clips were placed in the celiac arteries of the rats in the GIRD and GIR groups. Ischemia was created by keeping the clips closed for one hour. Afterward, the clips were removed and reperfusion was achieved for three hours. The sham operation was performed on the GSG group. Then, all animals were euthanized with 120 mg/kg ketamine. Malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD) catalase (CAT) and interleukin-6 (IL-6) levels were determined in the excised gastric tissues. All tissues were also analyzed histopathologically. Result: When the GIR group was compared with the GSG, an increase in MDA and IL-6 levels and a decrease in tGSH, SOD and CAT levels were observed (p less than 0.001). In addition, severe mucosal degeneration, congestion, polymorphonuclear leukocyte infiltration and mucosal edema were detected in the GIR group. Desloratine significantly inhibited both biochemical and histopathological changes (p less than 0.05).

Study on the difference and correlation between the contents and toxicity of aristolochic acid analogues in Aristolochia plants

Ethnopharmacological relevanceThe nephrotoxicity and carcinogenicity induced by traditional Chinese medicines (TCMs) containing aristolochic acids (AAs) and related compound preparations have greatly limited their clinical application. While the toxicity of AA-I and AA-II is relatively clear, there are marked differences in the toxic effects of different types of aristolochic acid analogues (AAAs). Thus, the toxicity of TCMs containing AAAs cannot be evaluated based on the toxicity of a single compound. Aim of the studyTo systematically investigate the toxicity induced by Zhushalian (ZSL), Madouling (MDL) and Tianxianteng (TXT) as representative TCMs derived from Aristolochia. Materials and methodsAAA contents in ZSL, MDL and TXT were determined using HPLC. Subsequently, mice were treated for 2 weeks with high (H) and low (L) dosages of TCMs containing total AAA contents of 3 mg/kg and 1.5 mg/kg, respectively. Toxicity was evaluated using biochemical and pathological examination and was based on organ indices. Correlations between AAA contents and induced toxicity were analysed using multiple methods. ResultsOf the total AAA content, ZSL contained mainly AA-I and AA-II (>90%, of which AA-I accounted for 49.55%). AA-I accounted for 35.45% in MDL. TXT mainly contained AA-IVa (76.84%) and other AAAs accounted for <10%. Short-term toxicity tests indicated that ZSL and high-dose MDL induced obvious renal interstitial fibrosis and gastric injury, whereas TXT (high and low dosages) caused only slight toxicity. Correlation analysis suggested that AA-I might be the critical hazard factor for toxicity. ConclusionsThe toxicity of TCMs containing AAAs cannot be generalised. The toxicity of TXT is relatively low compared with those of ZSL and MDL. The toxicity of Aristolochia depends mainly on the AA-I content; therefore, control of AA-I levels in TCMs and related compound preparations is required to reduce the risk of toxicity associated with the use of Aristolochia herbs in clinical settings.

Honokiol, an inducer of sirtuin-3, protects against non-steroidal anti-inflammatory drug-induced gastric mucosal mitochondrial pathology, apoptosis and inflammatory tissue injury.

Mitochondrial oxidative stress, inflammation and apoptosis primarily underlie gastric mucosal injury caused by the widely used non-steroidal anti-inflammatory drugs (NSAIDs). Alternative gastroprotective strategies are therefore needed. Sirtuin-3 pivotally maintains mitochondrial structural integrity and metabolism while preventing oxidative stress; however, its relevance to gastric injury was never explored. Here, we have investigated whether and how sirtuin-3 stimulation by the phytochemical, honokiol, could rescue NSAID-induced gastric injury. Gastric injury in rats induced by indomethacin was used to assess the effects of honokiol. Next-generation sequencing-based transcriptomics followed by functional validation identified the gastroprotective function of sirtuin-3. Flow cytometry, immunoblotting, qRT-PCR and immunohistochemistry were used measure effects on oxidative stress, mitochondrial dynamics, electron transport chain function, and markers of inflammation and apoptosis. Sirtuin-3 deacetylase activity was also estimated and gastric luminal pH was measured. Indomethacin down-regulated sirtuin-3 to induce oxidative stress, mitochondrial hyperacetylation, 8-oxoguanine DNA glycosylase 1 depletion, mitochondrial DNA damage, respiratory chain defect and mitochondrial fragmentation leading to severe mucosal injury. Indomethacin dose-dependently inhibited sirtuin-3 deacetylase activity. Honokiol prevented mitochondrial oxidative damage and inflammatory tissue injury by attenuating indomethacin-induced depletion of both sirtuin-3 and its transcriptional regulators PGC1α and ERRα. Honokiol also accelerated gastric wound healing but did not alter gastric acid secretion, unlike lansoprazole. Sirtuin-3 stimulation by honokiol prevented and reversed NSAID-induced gastric injury through maintaining mitochondrial integrity. Honokiol did not affect gastric acid secretion. Sirtuin-3 stimulation by honokiol may be utilized as a mitochondria-based, acid-independent novel gastroprotective strategy against NSAIDs.

Changes in Protease-Activated Receptor and Trypsin-1 Expression Are Involved in the Therapeutic Effect of Mg2+ Supplementation in Type 2 Diabetes-Induced Gastric Injury in Male Adult Rats.

Gastric inflammation is common and usually severe in patients with type 2 diabetes mellitus (T2DM). Evidence suggests protease-activated receptors (PARs) are a link between inflammation and gastrointestinal dysfunction. Given that magnesium (Mg2+) deficiency is a highly prevalent condition in T2DM patients, we assessed the therapeutic role of Mg2+ on the factors involved in gastric inflammation in T2DM. A rat model of T2DM gastropathy was established using a long-term high-fat diet + a low dose of streptozocin. Twenty-four rats were divided into control, T2DM , T2DM + insulin (positive control), and T2DM + Mg2+ groups. At the end of 2-month therapies, changes in the expression of gastric trypsin-1, PAR1, PAR2, PAR3, PI3K/Akt, and COX-2 proteins were measured by western blot. Hematoxylin and eosin and Masson's trichrome staining were used to detect gastric mucosal injury and fibrosis. The expression of trypsin-1, PAR1, PAR2, PAR3, and COX-2 increased in diabetes, and Mg2+/insulin treatment strongly decreased their expression. The PI3K/p-Akt significantly decreased in T2DM, and treatment with Mg2+/insulin improved PI3K in T2DM rats. Staining of the gastric antrum tissue of the insulin/Mg2+-treated T2DM rats showed a significantly minimal mucosal and fibrotic injury compared with those of rats from the T2DM group. Mg2+ supplement, comparable to insulin, via decreasing PARs expression, mitigating COX-2 activity, and decreasing collagen deposition could exert a potent gastroprotective effect against inflammation, ulcer, and fibrotic development in T2DM patients.

Fucoidan mitigates gastric ulcer injury through managing inflammation, oxidative stress, and NLRP3-mediated pyroptosis

This study aimed to elucidate the gastro-protective effect of fucoidan against ethanol-induced gastric ulcer mediated via NLRP3-induced pyroptosis as an underlying mechanism, not yet assessed in prior research. Forty-eight male Albino mice were divided into six groups: Group I (normal control), group II (Ulcer/ethanol control), group III (Omeprazole + ethanol), group IV (fucoidan 25 mg + ethanol), group V (fucoidan 50 mg + ethanol) and group VI (fucoidan only). Fucoidan was administered orally for seven consecutive days followed by ulcer induction by a single oral dose of ethanol. Using colorimetric analysis, ELISA, qRT-PCR, histological assessment, and immunohistochemical studies, the results revealed that ethanol-induced ulcer exhibited an ulcer score of 42.5 ± 5.1 and a significant increase (p < 0.05) in malondialdehyde (MDA), nuclear factor kappa B (NF-κB), and interleukin 6 (IL-6) with a significant decrease in the gastro-protective mediators, prostaglandin E2 (PGE2), superoxide dismutase (SOD) and glutathione (GSH), accompanied with an increase in NLRP3, interleukin 1β (IL-1β), interleukin 18 (IL-18), caspase 1, caspase 11, gasdermin D, and toll-like receptor 4 (TLR4), compared with the normal control. Pre-treatment with fucoidan showed a comparable result with omeprazole. Additionally, pre-treatments elevated the levels of the gastro-protective mediators and lessened oxidative stress, relative to the positive control findings. Conclusively, fucoidan has a promising gastro-protective role by inhibiting inflammation and pyroptosis.

Gastroprotective effects of Polygonatum odoratum in rodents by regulation of apoptotic proteins and inflammatory cytokines

In an increasing interest in natural antiulcer compounds that may have gastric healing effects and possibly prevent ulcer recurrence, Polygonatum odoratum appears as a strong candidate. The gastroprotective potentials of P. odoratum rhizome extract (PORE) were explored on ethanol-induced gastric ulceration in rats. Sprague Dawley rats were caged in 5 groups, normal and ulcer control rats received CMC (1% carboxymethyl cellulose). Omeprazole (20 mg/kg) was given to reference Rats. Experimental rats were treated with 250 mg/kg and 500 mg/kg PORE, respectively. After an hour, the normal control rats received 1% CMC, whereas rat groups 2–5 were given absolute ethanol by oral gavage. After 60 min, rats received anesthesia and were sacrificed. Dissected gastric tissue was analyzed by histopathological and immunohistochemical techniques. PORE treatment significantly lowered the ethanol-induced gastric injury, as shown by up-surging gastric pH and mucus content, reduced leukocyte infiltration, lower ulcerative areas in mucosal layers, and increased antioxidants (SOD and CAT) and (MDA) levels. Furthermore, PORE pre-treated rats showed significantly increased expression of the Periodic acid-Schiff (PAS), HSP-70 protein, and decreased Bax protein in their gastric epithelial layers. PORE treatment showed an important regulation of inflammatory cytokines shown by decreasing the TNF-a, and IL-6 and increasing the IL-10 values. The detected biological activity of PORE is encouraging and presents the scientific evidence for its traditional use as a gastroprotection agent however further studies are required to determine the exact phytochemicals and mechanism pathway responsible for this bioactivity.

Gastroprotective effect of electrical spinal cord stimulation may be mediated by glucocorticoids produced in response to this stimulation

We demonstrated previously that stress-induced glucocorticoids are gastroprotective hormones but not ulcerogenic ones (Filaretova et al., 2016). Recently electrical spinal cord stimulation began to be used for both experimental studies of motor functions regulation and rehabilitation of motor functions in patients with spinal cord injury (Gerasimenko et al., 2021; Moshonkina et al., 2016). The spinal cord stimulation directed to the activation of spinal locomotor related networks affected visceral systems as well. Recently in our teamwork we have shown that the electrical spinal cord stimulation can cause an increase in blood glucocorticoid level accompanied by a gastroprotective effect (Filaretova et al., 2022). The aim of the present work was to verify the hypothesis that the gastroprotective effect of the electrical spinal cord stimulation may be mediated by glucocorticoids produced in response to this stimulation. Gastric injury was induced in anesthetized rats by prolonged gastric ischemia/reperfusion (I/R, 30 min occlusion of celiac artery followed by 3 h of reperfusion) or indomethacin administration (IM, 35 mg/kg, sc). For spinal stimulation, stainless steel wire electrodes were fixed in fasciae between T11-12 and L1–L2 vertebrae of anesthetized animals. Motor evoked responses in hindlimbs muscles to spinal stimulation were recorded. Spinal stimulation at 30 Hz was carried out with a subthreshold current for inducing muscle contractions (80% of the threshold). Sham-stimulated (control) rats were subjected to the same manipulations except for the stimulation itself. To test the participation of glucocorticoids in the gastroprotective effect of the stimulation, two approaches were used: pretreatment by the inhibitor of glucocorticoid synthesis, metyrapone (30 mg/kg, i.p.) and the antagonist of glucocorticoid receptors RU-38486 (20 mg/kg, i.p.). The concentration of corticosterone in blood plasma was determined using commercial ELISA kits. In control rats the spinal cord stimulation resulted in an increase of blood corticosterone level 1 h later. The spinal stimulation, applied 1 h before the onset of ulcerogenic stimuli, also significantly attenuated gastric erosion formation induced by I/R and IM as well. Metyrapone injected shortly before the stimulation caused a fast inhibition of corticosterone response and reversed the gastroprotective effect stimulation. The gastroprotective effect of the stimulation was also prevented by the pretreatment rats with glucocorticoid receptor antagonist RU-38486. The obtained results indicate on contribution of glucocorticoids to gastroprotective effect of spinal cord stimulation. In conclusion, the findings support the hypothesis that the gastroprotective effect of the electrical spinal cord stimulation may be mediated by glucocorticoids produced in response to this stimulation. The study was supported by the Ministry of Education and Science of the Russian Federation (agreement No. 075-15-2020-921 for the creation and development of the world-class scientific center “Pavlov Center “Integrative Physiology - to medicine, high-tech healthcare and technologies of stress resistance”). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Oesophageal and gastric injuries caused by transoesophageal probe manipulation in patients undergoing transcatheter edge-to-edge repair for tricuspid regurgitation.

Oesophageal and gastric injuries caused by transoesophageal probe manipulation in patients undergoing transcatheter edge-to-edge repair for tricuspid regurgitation.

Ximenia americana L.: Chemical Characterization and Gastroprotective Effect

Ximenia americana L., popularly known in Brazil as “ameixa do-mato, ameixa-brava, and ameixa-do-sertão,” is widely used in folk medicine to treat several intestinal disorders. The present study assessed the potential mechanisms of action underlying the gastroprotective activity of the hydroethanolic extract of Ximenia americana L. (EHXA) stem bark. The acute toxicity of EHXA was estimated, and later, the gastroprotective effect in mice was assessed through acute models of gastric lesions induced by acidified or absolute ethanol and indomethacin, where the following mechanisms were pharmacologically analyzed: the involvement of prostaglandins (PG), histamine (H2) receptors, ATP-dependent potassium channels, sulfhydryl groups (SH), α2 adrenergic receptors, nitric oxide (NO), myeloperoxidase (MPO), gastric mucus production, and acetylcholine-mediated intestinal motility. Regarding toxicity, EHXA did not cause deaths or signs of toxicity (LD50 greater than or equal to 2000 mg/kg/p.o.). When the gastroprotective effect was assessed, EHXA (50, 100, and 200 mg/kg/p.o.) reduced the rate of lesions induced by acidified ethanol by 65.63; 53.66, and 58.02% in absolute ethanol at 88.91, 78.82, and 74.68%, respectively, when compared to the negative control group. In the indomethacin-induced gastric injury model, the reductions were 84.69, 55.99, 55.99, and 42.50%, respectively. The study revealed that EHXA might stimulate mucus production and reduce intestinal motility through SH groups, NO production, and activation of α2 adrenergic receptors. The results indicated that EHXA had significant gastroprotective activity in the evaluated models. However, further investigation is required to elucidate the cellular and molecular events underlying the action of EHXA components and to correlate them with the modulation of the signaling pathways, as demonstrated by the current pharmacological approach. Therefore, the results demonstrated in the present study, as well as previously reported findings, support the recommendation of using this species in traditional communities in Brazil.

Effect of ultrasonic modification on the protective activity of Flammulina velutipes polysaccharide to prevent ethanol-induced injury on GES-1 cells

Flammulina velutipes (F. velutipes) polysaccharides were modified by ultrasound at the rated power of 150 W and 900 W. The monosaccharide composition, ultraviolet-visible, and Fourier transform infrared spectral characteristics of F. velutipes polysaccharides (FVP) and their ultrasonic modification products (U-FVPs) were determined. The protective effects of FVP and U-FVPs on human gastric mucosal cells GES-1 were confirmed for the first time. The mole ratios of glucose and galactose were decreased and the mole ratio of mannose was increased after ultrasonic modification. Compared with the original FVP and the FVP modified by ultrasound of 150 W (U-FVP1), the FVP modified by ultrasound of 900 W (U-FVP2) could better prevent ethanol-induced damage to GES-1 cells. With increasing ultrasound intensity, the protective effect of FVPs on GES-1 cells was significantly enhanced by more effective prevention of intracellular reactive oxygen species (ROS) production and more promotion of expression of triglyceride factor 2 (TFF2), prostaglandin E2 (PGE2), epidermal growth factor (EGF), and transforming growth factor β1 (TGF-β1) mRNA. The ultrasonic modification might be an effective way to develop novel F. velutipes polysaccharides that could effectively resist the gastric injury caused by excessive alcohol consumption.

Low dose administration of mature silkworm powder induces gastric mucosal defense factors in ethanol-induced gastric injury rat model.

Gastric mucosa is important to protect the gastric damage against external factors. We previously reported the gastro-protective effects of steamed and freeze-dried mature silkworm larval powder (SMSP) in ethanol-treated rats. However, the factors that promote mucosal formation still remain unclarified. In this study, we evaluated the effect of SMSP on the restoration and maintenance of gastric mucosal layer as well as anti-inflammatory response in ethanol-induced stomach injury in rats. A significant decrease of ulcer indexes, histopathological scores and pro-inflammatory cytokine levels was observed in SMSP-treated group. In addition, SMSP protected the mucosal layer from ethanol-induced gastric damage by increasing the expression of nitric oxide synthases and heat shock proteins, along with promoting genes related gastric mucosal protection and biosynthesis including mucin 5AC and trefoil factors. These results demonstrate that SMSP attenuates the pro-inflammatory responses and strengthens the gastric mucosal layer, thus exhibiting gastro-protective effect against ethanol-induced gastric injury in rats.

MP42-13 ROBOTIC NON-TRANSECTING URETERAL REIMPLANTATION: A MULTI-INSTITUTIONAL EXPERIENCE

You have accessJournal of UrologyCME1 Apr 2023MP42-13 ROBOTIC NON-TRANSECTING URETERAL REIMPLANTATION: A MULTI-INSTITUTIONAL EXPERIENCE Brian Chao, David Strauss, Matthew Lee, Teona Iarajuli, Jennifer Nguyen, Ashley Alford, Michael Stifelman, Daniel Eun, and Lee Zhao Brian ChaoBrian Chao More articles by this author , David StraussDavid Strauss More articles by this author , Matthew LeeMatthew Lee More articles by this author , Teona IarajuliTeona Iarajuli More articles by this author , Jennifer NguyenJennifer Nguyen More articles by this author , Ashley AlfordAshley Alford More articles by this author , Michael StifelmanMichael Stifelman More articles by this author , Daniel EunDaniel Eun More articles by this author , and Lee ZhaoLee Zhao More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003280.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Robotic non-transecting ureteroneocystostomy (reimplantation) is an efficacious alternative to conventional reimplantation for mid- to distal ureteral strictures. We sought to update our multi-institutional experience with this technique and analyze intermediate-term outcomes. METHODS: We retrospectively reviewed a multi-institutional database of robotic ureteral reconstruction (CORRUS, or Collaborative of Reconstructive Robotic Ureteral Surgery) for patients undergoing robotic non-transecting reimplantation. Demographic, perioperative, and postoperative data were captured and reported using descriptive statistics. The primary outcome of interest was freedom from recurrent ureteral stenosis, defined as the absence of obstructive findings on follow-up imaging. Minimum follow-up duration for inclusion was three months. RESULTS: We identified 50 patients (comprising 55 ureters) who underwent robotic non-transecting ureteroneocystostomy between 2016 and 2022. Demographic, perioperative, and postoperative data are shown in the accompanying Table 1. Median stricture length was 2.8 cm (IQR 1–4). 17 patients (34%) had a history of radiation and 28 (56%) had prior abdominal or pelvic surgeries. 15 patients (30%) failed endoscopic stricture management; three (6%) failed prior reconstructive attempts. There was one intraoperative complication, a gastric injury repaired primarily by general surgery without subsequent sequelae. There were no immediate (≤30 days) postoperative complications. Over a median follow-up of 17.1 months (7.2–32.0), 47 patients (94%) comprising 52 ureters (95%) remained free from recurrent stricture disease. CONCLUSIONS: Our updated experience reaffirms the safety and efficacy of robotic non-transecting ureteral reimplantation. Despite a high proportion of patients with complex stricture disease, reimplantation was accomplished with minimal morbidity, satisfactory patency rates, and durable outcomes. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e572 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Brian Chao More articles by this author David Strauss More articles by this author Matthew Lee More articles by this author Teona Iarajuli More articles by this author Jennifer Nguyen More articles by this author Ashley Alford More articles by this author Michael Stifelman More articles by this author Daniel Eun More articles by this author Lee Zhao More articles by this author Expand All Advertisement PDF downloadLoading ...

Esophageal and Gastric Stricture Formation Following Corrosive Ingestion in Our Local Population

Corrosive substances are defined as chemicals which cause injury upon coming in contact with living tissues such as the skin, gastrointestinal tract, respiratory tract and eyes. These include acids, alkalis, oxidizing agents, hydrocarbons among others. Objective: To determine the frequency and difference in the frequency of upper gastrointestinal stricture formation following corrosive ingestion in the gastroenterology unit of Lady Reading Hospital, Peshawar. Methods: This cross- sectional study was held in the Gastroenterology unit of Lady Reading Hospital, Peshawar from 16th July, 2019 to 16th Jan, 2019. Detailed history was taken from the patient and the container of the chemical ingested was examined to find out the duration since ingestion, amount of chemical ingested, and the type of chemical ingested (acid or alkali). Results: Mean and SD for age was 35 ± 5.55. Mean and SDs for duration since ingestion. Mean and SDs for amount of corrosive ingestion was 24 ± 1.54. 50 (34.48%) patients were recorded in 10-25 years’ age group and 95 (65.51%) patients were recorded in 26-40 years’ age group. 97 (66.89%) patients were male, and 48 (33.10%) patients were female. 41 (28.27%) patients had acidic corrosion and 104 (71.72%) patients had alkali corrosion. As per frequencies and percentages for stricture formation, 57 (39.31%) patients had stricture formation. Conclusions: Although the mortality and morbidity of corrosive gastric injuries is high, the key to improve the survival is early identification of perforation, maintenance of nutrition and control of sepsis.

Investigation of the curative effects of Hypericum perforatum (St. John's Wort) and Rosa spinosissima (Black rosehip) on rats in an indomethacin-induced gastric peptic ulcer model

In this study, histopathological and immunohistochemical evaluations were made on the damage to the gastric tissue in the gastric peptic ulcer model induced by indomethacin, and it was investigated whether the plants Hypericum perforatum and Rosa spinosissima have a therapeutic effect. In order to create an ulcer model, 25mg/kg indomethacin was administered orally to the rats in the other groups, except the sham control group, in 2 doses, 24 hours apart. In the treatment groups, the first dose of indomethacin was given an hour after the second dose, and the second dose of plant oils was given orally 24 hours later. Then, 1 hour later, the rats were sacrificed. In the histopathological evaluation, sections belonging to the indomethacin control group showed intense degeneration of both epithelial and mucosal glands in the gastric mucosa. Edema and bleeding were also present in the lamina propria and submucosa layers. These observed damages were significantly reduced in the RS+HP-1 and RS+HP-2 groups. As a result of the immunohistochemical evaluations, it was observed that the group with the highest Bax immunoreactivity was the indomethacin control group, and the groups with the lowest were RS+HP-1 and RS+HP-2. It was determined that the group with the lowest Bcl-2 immunoreactivity was the indomethacin control group, and the groups with the highest were RS+HP-1 and RS+HP-2. The results showed that Hypericum perforatum and Rosa spinosissima plants have therapeutic and anti-apoptotic effects on gastric injury.

Polyaspartic Acid-Stabilized CaCO3-Containing In Situ Hydrogel for Protection and Treatment of Gastric Ulcer.

The lack of effective oral drug delivery systems to treat gastric ulcer is an urgent challenge in clinical practice. Herein, a gastric acid pH-responsive hydrogel of curcumin/sodium alginate/polyaspartic acid@CaCO3 (Cur/SA/PC) was developed for sustained release of Cur, exerting effective protection and treatment of gastric ulcers. The in vitro gelatinization properties and the corresponding gel characteristics of the SA/PC delivery system demonstrated the successful construction of the in situ hydrogel with uniform strength. The cellular uptake illustrated the successful uptake and sustained release of Cur. Besides, Cur effectively inhibited NLRP3-mediated pyroptosis both in vitro and in vivo, exhibited an excellent pro-healing effect by regulating the PI3K/Akt signaling pathway, and alleviated acetic acid-induced chronic gastric injury in rats. Moreover, the relative bioavailability of Cur in the SA/PC hydrogel could effectively increase in the pharmacokinetic study. Importantly, the protective barrier formed by the SA/PC hydrogel could effectively protect against alcohol-induced acute gastric ulcers in rats. Overall, the designed SA/PC oral delivery system is a promising strategy to overcome gastric barriers for oral drug delivery.

Selective accumulation of ionic nanocrystal H2 storage system as an in situ H2/boric acid nanogenerator fights against ethanol-induced gastric ulcers

Ethanol is a potential causative factor of gastric ulcers, which are associated with gastric injury and the overproduction of reactive oxygen species. Molecular hydrogen (H2) is reportedly a benign antioxidant and boric acid is an effective medication in repairing deep wounds. In this work, a nanoparticle system that consists of potassium borohydride ionic nanocrystals (KBH4 NCs) with a high H2 storage capacity is developed for the treatment and prevention of ethanol-induced gastric ulcers in mice. H2-rich water (HRW) is used as a control. Since the evolution of gaseous H2 from the HRW is abrupt, most of the evolved H2 gas is lost to the surrounding environment before and during oral administration. By contrast, KBH4 NCs can be trapped at the defect sites of ulcerated regions, reacting with the gastric fluid to generate sustainably gaseous H2 and boric acid, mitigating oxidative stress and excessive inflammation in tissues and repairing the gastric injury. Additionally, the protection that is afforded by gastric mucosa against ethanol-induced damage is stronger in mice that have been pretreated with KBH4 NCs than in those that have been pretreated with HRW, indicating the protective effect of KBH4 NCs. Overall, the data suggest that the as-developed KBH4 NCs are a promising oral formulation for the effective management of gastric ulcers.

Integrating in vivo and in silico approaches to investigate the potential of Zingiber roseum rhizome extract against pyrexia, inflammation and pain

Zingiber roseum is a perennial herb in the Zingiberaceae family. The plant is native to Bangladesh, and rhizomes are frequently used in traditional medicine to cure gastric ulcers, asthma, wounds, and rheumatic disorders. Therefore, the present study aimed to analyse the antipyretic, anti-inflammatory, and analgesic properties of Z. roseum rhizome to confirm its efficacy in traditional applications. After 24 h of treatment, ZrrME (400 mg/kg) showed a considerable drop in rectal temperature (3.42°F) compared to standard paracetamol (5.26°F). At both doses (200 and 400 mg/kg), ZrrME showed a substantial dose-dependent decrease in paw oedema. However, after 2, 3 and 4 h of testing, the extract (200 mg/kg) had a lower anti-inflammatory response than standard indomethacin, whereas the higher dose (400 mg/kg) of rhizome extract had a more robust response compared to standard. ZrrME also showed substantial analgesic activity against all in vivo analgesic test models. The in vivo findings were further evaluated by in silico study of our previously identified compounds of ZrrME with the cyclooxygenase-2 enzyme (3LN1). The substantial binding energy (ranges from-6.2 to-7.7 Kcal/mol) of the polyphenols (excluding catechin hydrate) to the COX-2 enzyme affirm the in vivo test results of the present studies. In addition, the compounds were found effective as antipyretic, anti-inflammatory, and analgesic agents, according to the biological activity prediction software. Both in vivo and in silico results demonstrated promising antipyretic, anti-inflammatory, and pain-relieving effects of Z. roseum rhizome extract, which corroborate the claim of its traditional uses.

Camellia oil (Camellia oleifera Abel.) alleviates gastric injury induced by ethanol associated with modulation of gut microbiota in mice

Oil from Camellia oleifera Abel. seed is a popular edible oil in Asia, which has gained much attention for its medicinal applications on relieving various inflammation, however, the mechanism is still unknown. The present study was to investigate the gastroprotective effect of camellia oil against ethanol-induced gastric mucosal injury in mice. The results showed that camellia oil pretreatment significantly reduced gastric ulcer injury. A remarkable inhibited oxidative stress by reducing the concentration of malondialdehyde and a significant decrease of the levels of pro-inflammatory factors in gastric tissue were observed in camellia oil pretreated group. In addition, camellia oil improved the diversity of gut microbiota and changed the community structure and composition by increasing Bacteriodes and Dorea. And the feces metabolomics found that metabolism of cofactors and vitamins, and lipid, carbohydrate and amino acid metabolism were modulated by admiration of camellia oil. Taken together, the findings of this study suggested that camellia oil could ease the ethanol-induced gastric mucosal injury via the improvement of anti-oxidant and anti-inflammatory status, as well as the regulation of gut microbiota and its metabolites.

Galangin protects gastric mucosa from indomethacin induced injury via scavenging ROS and inhibition of PKC, Akt, and NF κB protein expressions

Purpose: To investigate the mechanism of action of galangin (GAL) against indomethacin (Indo)-induced gastric injury.&#x0D; Methods: Ten micromolar GAL with 2 mM Indo or 0.5 mM L-NAME or 2 mM propargylglycine were co-administered to human gastric mucosal epithelial cells GES-1 for 24 h. Cell viability assay and reactive oxygen species (ROS) test were conducted with commercial kits. Protein expressions of constitutive and inducible nitric oxide synthase (cNOS and iNOS, respectively), and cystathionine-γ-lyase (CSE) in GSE-1 cells were investigated by western blot. After 100 - 300 mg/kg, GAL was daily administered to rats for 5 days, and 30 mg/kg Indo was administered to induce gastric injury. Protein expressions of endothelial NOS (eNOS), iNOS, CSE, nuclear factor (NF)-κB, PKC, Akt, phospho-eNOS (Ser-1177), and phospho-eNOS (Thr-495) were investigated by western blot.&#x0D; Results: Galangin ameliorated the proliferative inhibitions of Indo, propargylglycine, and L-NAME on GSE-1 cells (p &lt; 0.05), rapidly scavenged ROS, and increased cNOS protein expressions (p &lt; 0.05). Galangin (300 mg/kg) inhibited protein expressions of iNOS (p &lt; 0.01), NF-κB, Akt, and PKC (p &lt; 0.05), inhibited the Ser-1177 and Thr 495 phosphorylation of eNOS, elevated eNOS and CSE protein expressions (p &lt; 0.001).&#x0D; Conclusion: Galangin protects gastric mucosa from Indo by scavenging ROS and inhibiting protein expressions of Akt and PKC. The inhibition leads to Ser-1177 and Thr 495 dephosphorylation of eNOS, thereby prolonging eNOS activity. Besides, GAL inhibits iNOS-produced NO by inhibiting NF-κB to ameliorate the inflammatory reaction induced by Indo.

EPIDEMIOLOGIE DU CANCER GASTRIQUE : EXPERIENCE D’UN CENTRE HOSPITALIER UNIVERSITAIRE D’ANTANANARIVO EPIDEMIOLOGY OF GASTRIC CANCER: EXPERIENCE OF AN UNIVERSITY HOSPITAL CENTER IN ANTANANARIVO

Background: The management of gastric cancer is a major challenge in low-income countries. The aim of this study was to describe the epidemiological, clinical and therapeutic aspects of gastric cancer in the Visceral Surgery ward of the Centre Hospitalier Universitaire Joseph Ravoahangy Andrianavalona in Antananarivo. Materials and Method: This was a descriptive retrospective study conducted from January 2010 to December 2016. All patients over 18 years of age hospitalized for gastric cancer with histological confirmation were included in the study. The epidemiological, clinical and therapeutic methods were analyzed. Outcome assessment will not be the subject of this study. Results: Gastric cancer was confirmed in 68 patients. The average age was 56.5. Helicobacter pylori infection was the main risk factor. Gastrointestinal bleeding and chronic epigastric pain were the most revealing clinical manifestations. Ulcerous and exuberant gastric injuries were the most frequent, preferentially located in the pyloric antrum (n = 38). Surgery was curative in 24 patients, palliative in 13 patients. Four patients received primary chemotherapy and 27 refused to continue treatment when the diagnosis was announced. Papillary adenocarcinoma was the most common histological type (n = 32). Conclusion: gastric cancer is discovered at an advanced stage in our center. Currently, all age groups are exposed to risk factors. Endoscopic screening and eradication of Helicobacter Pylori infection should be mandatory. Multidisciplinarity is essential in the management.