Rat Stomach Research Articles

Stomach perforation-induced general occlusion/occlusion-like syndrome and stable gastric pentadecapeptide BPC 157 therapy effect.

Using rat stomach perforation as a prototypic direct lesion applied in cytoprotection research, we focused on the first demonstration of the severe occlusion/ occlusion-like syndrome induced by stomach perforation. The revealed stomach-induced occlusion/occlusion-like syndrome corresponds to the previously described occlusion/occlusion-like syndromes in rats suffering multicausal pathology and shared severe vascular and multiorgan failure. This general point was particularly reviewed. As in all the described occlusion/occlusion-like syndromes with permanent occlusion of major vessels, peripheral and central, and other similar noxious procedures that severely affect endothelium function, the stable gastric pentadecapeptide BPC 157 was resolving therapy. To reveal the stomach perforation-induced general occlusion/occlusion-like syndrome and BPC 157 therapy effect. The procedure included deeply anesthetized rats, complete calvariectomy, laparotomy at 15 min thereafter, and stomach perforation to rapidly induce vascular and multiorgan failure occlusion/occlusion-like syndrome. At 5 min post-perforation time, rats received therapy [BPC 157 (10 µg or 10 ng/kg) or saline (5 mL/kg, 1 mL/rat) (controls)] into the perforated defect in the stomach). Sacrifice was at 15 min or 60 min post-perforation time. Assessment (gross and microscopy; volume) included: Brain swelling, peripheral vessels (azygos vein, superior mesenteric vein, portal vein, inferior caval vein) and heart, other organs lesions (i.e., stomach, defect closing or widening); superior sagittal sinus, and peripherally the portal vein, inferior caval vein, and abdominal aorta blood pressures and clots; electrocardiograms; and bleeding time from the perforation(s). BPC 157 beneficial effects accord with those noted before in the healing of the perforated defect (raised vessel presentation; less bleeding, defect contraction) and occlusion/occlusion-like syndromes counteraction. BPC 157 therapy (into the perforated defect), induced immediate shrinking and contraction of the whole stomach (unlike considerable enlargement by saline application). Accordingly, BPC 157 therapy induced direct blood delivery via the azygos vein, and attenuated/eliminated the intracranial (superior sagittal sinus), portal and caval hypertension, and aortal hypotension. Thrombosis, peripherally (inferior caval vein, portal vein, abdominal aorta) and centrally (superior sagittal sinus) BPC 157 therapy markedly reduced/annihilated. Severe lesions in the brain (swelling, hemorrhage), heart (congestion and arrhythmias), lung (hemorrhage and congestion), and marked congestion in the liver, kidney, and gastrointestinal tract were markedly reduced. We revealed stomach perforation as a severe occlusion/occlusion-like syndrome, peripherally and centrally, and rapid counteraction by BPC 157 therapy. Thereby, further BPC 157 therapy may be warranted.

Effect of Omega3 in rat stomach induced peptic ulcer by ethanol

Effect of Omega3 in rat stomach induced peptic ulcer by ethanol

Characterization of rat gastric myogenic contractions and modulation by oxytocin and arginine-vasopressin

BackgroundInterstitial cells of Cajal generate slow wave gastric electrical activity, initiating spontaneous muscle contractions. This becomes dysrhythmic during nausea when [Arg8]-vasopressin (AVP) is also released. In human stomach AVP increased spontaneous contraction activity and muscle tone, not neuronally-mediated contractions. Rodents cannot vomit, releasing the related hormone, oxytocin (OT) instead. We hypothesised that rat stomach would behave differently. Experimental approachSpontaneous and electrically-evoked (EFS) contractions were measured in rat forestomach and antrum circular muscle. Custom software defined spontaneous contractions by analysing eight motility parameters. ResultsThe forestomach was quiescent. Irregular antrum contractions became regular adjacent to the pylorus (1.7 ± 0.4 mN; 1.2 ± 0.1 contractions/min, n = 12). These were unaffected by tetrodotoxin (10−6 M), atropine (10−6 M) and L-NAME (3 × 10−4 M). In both regions, AVP (pEC50∼9.0) and OT (∼0.5 log10-unit less potent) caused contraction (greater in antrum), competitively antagonized by, respectively, SR49059 (pKB∼9.5) and L371257 (pKB∼9.0), reduced by tetrodotoxin but unaffected by atropine. In the antrum, AVP and OT (∼2 log10-units less potent/efficacious) regularized and increased spontaneous contraction amplitude, frequency, rates of contraction/decay. In both regions, EFS-evoked contractions, abolished by atropine/tetrodotoxin, were reduced by AVP and OT, with AVP more potent and efficacious, particularly in forestomach. ConclusionIrregular spontaneous contractions of gastric antrum suggest variable ICC-muscle coupling. AVP and less potently, OT, enhanced frequency and force of contractions via V1A and OT receptors. Compared with human, differences in contraction regularity, potency and ability of AVP/OT to affect neuronal function suggests caution when using rat stomach to model ICC functions and nauseagenic stimuli.

Study of the antiulcer activity of garden cabbage extract on the chronic acetic ulcer model in rats

The aim of the study was to study the gastroprotective properties of the dry extract of garden cabbage in the model of chronic acetic ulcer in rats.
 Materials and methods. Chronic ulcerative lesions of the gastric mucosa of rats were modeled by introducing 0.05 ml of a 30 % solution of acetic acid into the subserous layer of the stomach wall. The dry extract of garden cabbage in a conditionally therapeutic dose of 50 mg/kg and reference drugs omeprazole and altan were administered intragastrically for 10 days, starting from the second day of the experiment. When choosing the duration of the course of treatment, we proceeded from the data that the effectiveness of the antiulcer action in the clinic is assessed after 10-12 days of treatment. The percentage of animals with ulcers in the group, the state of the gastric mucosa were evaluated, the ulcer index and antiulcer activity were calculated. To elucidate the possible mechanism of action of the extract, we studied its effect on synthetic processes in terms of the content of RNA and DNA in homogenates of the gastric mucosa by the spectrophotometric method by reaction with perchloric acid.
 Results. On the model of stomach damage, caused by acetic acid, a pronounced antiulcer activity of the extract (54.26) was established at the level of omeprazole (54.62). The maximum antiulcer activity (72.75) was revealed when using the combination of the extract with omeprazole, which, in terms of ulcerative effect, is superior to monotherapy with the extract, omeprazole and altan (35.08).
 Reparative regeneration is a component of an adaptive tissue reaction; under conditions of violation of the reparative potencies of the mucosa, chronic diseases of the gastrointestinal tract develop. Since the final goal of antiulcer therapy is the healing of the ulcer, and the basis of this process is reparative regeneration, the reparative properties of the extract have been studied. Under the influence of cabbage extract, the content of RNA and DNA in the mucosa probably increased by 2.8 and 2.4 times, respectively, at the same level with omeprazole. If possible, to activate the synthetic processes of DEGC and omeprazole, altan significantly prevailed.
 The most pronounced effect of enhancing reparative processes was established with the combined use of the extract and omeprazole, which turned out to be a significant increase in the content of RNA and DNA in the gastric mucosa by 3.2 and 2.9 times compared with the control.
 Conclusions. On the model of chronic damage to the stomach of rats, cabbage extract showed an antiulcer effect, the severity of which was not inferior to the comparison drug, the proton pump inhibitor omeprazole, and significantly exceeded the phytopreparation - altan. The combined use of the extract and omeprazole showed the highest preventive effect of preventing the negative effects of acetic acid on the gastric mucosa. One of the mechanisms of the gastroprotective action of the extract is its ability to enhance reparative processes in the gastric mucosa. The results obtained indicate the prospects for further research on the antiulcer properties of cabbage extract with a view to its use in the complex therapy of peptic ulcer

Gastroprotective effect of sumatriptan against indomethacin-, stress- and ethanol-induced gastric damage in male rats: Possible modulatory role of 5-hydroxytryptamine 1B/1D receptors and pro-inflammatory cytokines.

The current study was aimed to investigate the beneficial effect of sumatriptan, a 5-hydroxytryptamine 1B/1D (5HT1B/1D ) receptor agonist, on gastric ulcer in rats via stimulating 5HT1B/1D receptors and suppressing pro-inflammatory cytokines. Rats were allocated into three models of gastric ulcer: indomethacin (30 mg/kg, PO), water immersion restraint stress (WRS) and ethanol (5ml/kg PO). Animals were administered with sumatriptan (0.01, 0.1, 0.3 and 1mg/kg, i.p) 30 min before gastric ulcer induction. GR-127935 (0.01 mg/kg, i.p, a selective 5HT1B/1D antagonist) was administered 30 min before sumatriptan (0.1mg/kg) injection. Macroscopic assessments (J-score), ELISA analysis of tumour necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) and histopathological changes were performed on the rat's stomach tissues. Gastric ulcer induction in three models caused an increase in J-score, TNF-α, IL-1β and microscopic features. Sumatriptan (0.1mg/kg) significantly improved gastric injury induced by indomethacin, WRS and ethanol through the reduction in the J-score, TNF-α, IL-1β and microscopic lesions. Concurrent administration of GR-127935 (0.01 mg/kg) with sumatriptan (0.1mg/kg) reversed the gastroprotective effect of sumatriptan in three models. Sumatriptan possessed gastroprotective effects on indomethacin-, WRS- and ethanol-induced gastric damage in rats via the possible involvement of the 5HT1B/1D receptors.

Effects of Polygonum cognatum Meissn. extract on indomethacin induced gastric damage in rats

ABSTRACT We investigated the anti-ulcer activity of ethanol extracts of Polygonum cognatum on indomethacin induced gastric damage in rats. We evaluated the number of ulcer areas, oxidant and antioxidant parameters as well as histopathologic features in rat stomach. We measured the total antioxidant status of P. cognatum in concentrations from 1.56–100 mg/ml. P. cognatum extract inhibited indomethacin induced ulcer formation with an effect similar to a 20 mg/kg dose of the standard anti-ulcer drug, esomeprazole. All doses of P. cognatum extract exhibited positive effects on oxidative stress markers and histopathological features in the stomach tissue of rats. We suggest that the antioxidant activity of P. cognatum extract may be responsible for its gastroprotective effect and that P. cognatum extract may be a useful gastroprotective agent.

Elian granules alleviate precancerous lesions of gastric cancer in rats by suppressing M2-type polarization of tumor-associated macrophages through NF-κB signaling pathway

BackgroundPrecancerous lesions of gastric cancer (PLGC) refer to a kind of histopathological changes in the gastric mucosa that can progress to gastric cancer. Elian granules (ELG), a Chinese medicinal prescription, have achieved satisfactory results in the treatment of PLGC. However, the exact mechanism underlying the therapeutic effect of ELG remains unclear. Here, this study aims to explore the mechanism of ELG alleviating PLGC in rats.MethodsThe chemical ingredients of ELG were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). Specific Pathogen Free SD rats were randomly assigned to 3 groups: the control, model, and ELG groups. The 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) integrated modeling method was adopted to construct the PLGC rat model in groups except for the control group. Meanwhile, normal saline was used as an intervention for the control and model groups, and ELG aqueous solution for the ELG group, lasting 40 weeks. Subsequently, the stomach of rats was harvested for further analysis. Hematoxylin-eosin staining of the gastric tissue was conducted to assess the pathological changes. Immunofluorescence was carried out for the expression of CD68, and CD206 proteins. Real-time quantitative PCR combined with Western blot was conducted to analyze the expression of arginase-1(Arg-1), inducible nitric oxide synthase (iNOS), p65, p-p65, nuclear factor inhibitor protein-α (IκBα), and p-IκBα in gastric antrum tissue.ResultsFive chemical ingredients including Curcumol, Curzerenone, Berberine, Ferulic Acid, and 2-Hydroxy-3-Methylanthraquine were identified in ELG. The gastric mucosal glands of rats treated with ELG were orderly arranged, with no intestinal metaplasia and no dysplasia. Furthermore, ELG decreased the percentage of M2-type TAMs marked with CD68 and CD206 proteins, and the ratio of Arg-1 to iNOS in the gastric antrum tissue of rats with PLGC. In addition, ELG could also down-regulate the protein and mRNA expression of p-p65, p65, and p-IκBα, but up-regulate the expression of IκBα mRNA in rats with PLGC.ConclusionsThe results showed that ELG attenuates PLGC in rats by suppressing the M2-type polarization of tumor-associated macrophages (TAMs) through NF-κB signaling pathway.

Comparison effect of different combinations of metformin, atorvastatin, captopril and aspirin on oxidative stress markers of stomach and liver tissues of diabetic rats

Comparison effect of different combinations of metformin, atorvastatin, captopril and aspirin on oxidative stress markers of stomach and liver tissues of diabetic rats

Pharmacokinetics and tissue distribution of 12 major active components in normal and chronic gastritis rats after oral administration of Weikangling capsules

Ethnopharmacological relevanceWeikangling Capsules (WKLCs) have been used in the clinic for the treatment of gastrointestinal disorders for more than 30 years. However, the pharmacokinetic characteristics and tissue distribution of its major bioactive components in rats under different physiological and pathological conditions are unclear. Aim of the studyIn this study, we aimed to clarify the differences in pharmacokinetic parameters and tissue distribution of the major active components in WKLCs under physiological and pathological states. Materials and methodNormal and ethanol-induced chronic gastritis rats received 2.16 g/kg WKLCs by gavage, and urine, feces, plasma, and tissue (heart, liver, spleen, lung, kidney, stomach, and small intestine) samples were obtained. The active components in urine, feces and plasma were detected by ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). A rapid and sensitive analytical method, ultra-high-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (UHPLC-QTRAP-MS/MS), was established and validated to clarify and compare the pharmacokinetics and tissue distribution of the major active components in normal and chronic gastritis rats. ResultsA total of 36 chemical components in the feces, urine, and plasma of chronic gastritis rats were identified by UHPLC-Q-TOF-MS/MS. Among them, 20 were the prototype components of WKLCs, and 16 were metabolites. The pharmacokinetic characteristics and tissue distribution of 12 prototype components were successfully analyzed by UHPLC-QTRAP-MS/MS. The pharmacokinetic results showed that the Cmax, AUC0-t, and AUC0-∞ of paeoniflorin, glycyrrhizic acid, and glycyrrhetinic acid were distinctly higher than those of the other components in normal and chronic gastritis rats. Compared to normal rats, the Cmax, AUC0-t, and AUC0-∞ of albiflorin, liquiritin apioside, liquiritin, isoliquiritin, ononin, isoliquiritigenin, dactylorhin A, and glycyrrhizic acid were significantly increased in chronic gastritis rats (P < 0.05), while the Cmax, AUC0-t and AUC0-∞ of militarine and liquiritigenin had significantly lower decreases in chronic gastritis rats (P < 0.05). The results of the tissue distribution showed that the 12 components were widely distributed in the heart, liver, spleen, lung, kidney, stomach, and small intestine of rats, of which the liver, kidney, stomach, and small intestine were the main accumulative organs. Compared with normal rats, the concentrations of 12 components in the liver, kidney, stomach, and small intestine of chronic gastritis rats were widely higher than those of normal rats at the same time points. ConclusionThe pharmacokinetic characteristics and tissue distribution of 12 active components of WKLCs were comprehensively characterized and elucidated in normal and chronic gastritis rats. These findings laid a solid foundation for revealing the pharmacodynamic material basis of WKLCs in treating gastrointestinal disorders.

Experimental study on the toxicokinetics and gastrointestinal damage in rats poisoned with acute diquat poisoning at different exposure doses

To observe the toxicokinetic parameters, absorption characteristics and pathomorphological damage in different parts of the gastrointestinal tract of rats poisoned with different doses of diquat (DQ). Ninety-six healthy male Wistar rats were randomly divided into a control group (six rats) and low (115.5 mg/kg), medium (231.0 mg/kg) and high (346.5 mg/kg) dose DQ poisoning groups (thirty rats in each dose group), and then the poisoning groups were randomly divided into 5 subgroups according to the time after exposure (15 minutes and 1, 3, 12, 36 hours; six rats in each subgroup). All rats in the exposure groups were given a single dose of DQ by gavage. Rats in the control group was given the same amount of saline by gavage. The general condition of the rats was recorded. Blood was collected from the inner canthus of the eye at 3 time points in each subgroup, and rats were sacrificed after the third blood collection to obtain gastrointestinal specimens. DQ concentrations in plasma and tissues were determined by ultra-high performance liquid chromatography and mass spectrometry (UPHLC-MS), and the toxic concentration-time curves were plotted to calculate the toxicokinetic parameters; the morphological structure of the intestine was observed under light microscopy, and the villi height and crypt depth were determined and the ratio (V/C) was calculated. DQ was detected in the plasma of the rats in the low, medium and high dose groups 5 minutes after exposure. The time to maximum plasma concentration (Tmax) was (0.85±0.22), (0.75±0.25) and (0.25±0.00) hours, respectively. The trend of plasma DQ concentration over time was similar in the three dose groups, but the plasma DQ concentration increased again at 36 hours in the high dose group. In terms of DQ concentration in gastrointestinal tissues, the highest concentrations of DQ were found in the stomach and small intestine from 15 minutes to 1 hour and in the colon at 3 hours. By 36 hours after poisoning, the concentrations of DQ in all parts of the stomach and intestine in the low and medium dose groups had decreased to lower levels. Gastrointestinal tissue (except jejunum) DQ concentrations in the high dose group tended to increase from 12 hours. Higher doses of DQ were still detectable [gastric, duodenal, ileal and colonic DQ concentrations of 6 400.0 (1 232.5), 4 889.0 (6 070.5), 10 300.0 (3 565.0) and 1 835.0 (202.5) mg/kg respectively]. Light microscopic observation of morphological and histopathological changes in the intestine shows that acute damage to the stomach, duodenum and jejunum of rats was observed 15 minutes after each dose of DQ, pathological lesions were observed in the ileum and colon 1 hour after exposure, the most severe gastrointestinal injury occurred at 12 hours, significant reduction in villi height, significant increase in crypt depth and lowest V/C ratio in all segments of the small intestine, damage begins to diminish by 36-hour post-intoxication. At the same time, morphological and histopathological damage to the intestine of rats at all time points increased significantly with increasing doses of the toxin. The absorption of DQ in the digestive tract is rapid, and all segments of the gastrointestinal tract may absorb DQ. The toxicokinetics of DQ-tainted rats at different times and doses have different characteristics. In terms of timing, gastrointestinal damage was seen at 15 minutes after DQ, and began to diminish at 36 hours. In terms of dose, Tmax was advanced with the increase of dose and the peak time was shorter. The damage to the digestive system of DQ is closely related to the dose and retention time of the poison exposure.

Effect of Gallic Acid on Distant Organ Stomach in Intestinal Ischemia Reperfusion Injury

Aim: To examine the effects of gallic acid (GA) in the stomach in rats undergoing intestinal ischemia/reperfusion (IR) with Beclin -1 immunostaining.&#x0D; Material-Metod: 24 male Wistar albino rats were divided into control, IR and IR+GA groups. For the IR protocol, 60 minutes of ischemia and reperfusion were applied. The small intestines of the rats in the control group were removed by laparotomy and the abdomen was closed without applying anything else. Ischemia and reperfusion was applied to the superior mesenteric artery (SMA) for 60 minutes with a clamp in rats in the IR group. The blood flow was stopped with a clamp on the SMA of the rats in the IR+GA group and ischemia was applied for 60 minutes. 50 mg/kg gallic acid was given intraperitoneally to the animals, 60 minutes of reperfusion was performed, and the abdomen was closed. The stomach tissues were placed in paraffin blocks after routine histological follow-ups. Five micrometer-thick sections were taken from the paraffin blocks and stained with Hematoxylin-eosin and Beclin-1 immunostaining.&#x0D; Results: In the IR group, degeneration of gastric folds, apoptosis of epithelial cells and degeneration of lamina muscularis were observed. In the IR + GA group, gastric folds improved, but cell infiltration in the lamina propria and degeneration in the muscular layer were observed. Beclin-1 expression was positively observed in the surface epithelial cells and gastric glands in the control group. In the IR group, it was observed that the gastric folds were positive on the surface cells and negative in the submucosa, while in the IR + GA group, it was intensely expressed in the gastric epithelium and gastric glands.&#x0D; Conclusion: By increasing the expression of beclin-1, GA treatment induced autophagy in gastric mucosal cells, triggered the destruction of damaged cells and provided restoration of the mucosal layer.&#x0D; Keywords: Beclin-1, gallic acid, apoptosis

In vivo experimentally study the effect of Nigella Sativa silver nanoparticles for treatment of salmonella species causing diarrhea in ruminants

Salmonellais one of the main etiological agents of infectious diarrhea in large and small ruminants but emergence of multidrug-resistant (MDR) strains faster rate than previously, leads to develop of MDR strains among animals needs different alternative therapeutic strategies. Our study was aimed to evaluate the effects of Nigella sativa silver nanoparticles (NS AgNPs) on specific pathogen-free (SPF) Wister rats. Nigella sativa silver nanoparticles were prepared and confirmed their formation by optical observations, UV–Vis spectroscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Rats in group G2 were infected experimentally with Salmonella spp and treated with ciprofloxacin orally for duration of 6 days at a dose rat 10 mg/kg. On the other hand, rats in group G1 were infected with salmonella and treated for 20 days with NS AgNPs in oral dose of (10 mg/kg rats), and the results were compared to control groups G3 which received bacterial infection without treatment and G4 control negative. The results of optical observation, UV–Vis spectroscopy, TEM, and SEM revealed typical characteristics of prepared NS AgNPs. Liver, kidney function biomarkers, hematologic analysis, and histological examination the tissues of liver, kidney, and stomach of rat's model improved that NS AgNPs has antimicrobial effect and has the ability to decrease the inflammatory reaction caused by Salmonella spp infection. The results of our study indicate that NS AgNPs are effective in controlling MDR Salmonella spp in vivo without causing any adverse effects. Moreover, our findings suggest that reducing the use of antimicrobials could be a key factor in the fight against antimicrobial resistance and can provide valuable insights into identifying the most appropriate treatment strategies to tackle this issue effectively in the future.

Functional and structural mapping of inhibitory neurons in the rat stomach muscle

Functional gastrointestinal disorders such as gastroparesis and achalasia can be caused by changes in the stomach’s intrinsic neural circuitry, the enteric nervous system. We used electrophysiological, immunohistochemistry and lesion techniques to map the function and structure of this circuitry, to aid in novel neuromodulation therapies to treat these debilitating disorders. It is expected that a single enteric neuron innervates multiple smooth muscle cells, and that an increased stimulus recruits more axons, evoking a summated response at the autonomic neuromuscular junction. Strips of muscle from different stomach regions of rats were taken for in vitro intracellular electrophysiology recordings from the circular muscle layer. Both inhibitory and excitatory neuromuscular junction potentials (JP) were measured. Inhibitory transmission was antagonised by a combination of nitric oxide synthase inhibitors and purine receptor antagonists and excitatory transmission was substantially reduced by muscarinic block. The relative amplitudes of excitatory and inhibitory JPs were quantified across all regions of the stomach, in most cases the relative amplitude was halved 9 millimetres (mm) circumferentially from the stimulation site. In the antrum, the whole circumference can be affected simultaneously. Innervation effectiveness at all distances was graded with stimulus strength. Suggesting each individual smooth muscle cell received multiple neuronal inputs. However, the relative amplitudes varied depending on the stomach region. Localisation studies show that the numbers of inhibitory and excitatory neurons are similar however the distribution of myenteric ganglia within the stomach were uneven from the lesser to greater curvature. This potentially influences the relative JP amplitudes recorded from different regions. Response amplitudes recorded closest to the lesser curvature were smaller when compared to the site further circumferentially. Furthermore, our results indicate that this may not be the only factor leading to the variabilities in innervation. Lesion and immunohistochemistry studies indicate that axons of inhibitory and excitatory neurons branch and extend circumferentially and the innervation fields of several neurons overlap. Our electrophysiology shows that the degree of influence of excitatory neurons on the smooth muscle cell varies dependent on the region recorded. We conclude that inhibitory and excitatory neural influences extend around the gastric circumference and the effectiveness of inhibitory and excitatory influences can be graded by the recruitment of different numbers of motor neuron nerve terminals. This study was supported by NIH (SPARC) grant, The Virtual Stomach (OT2OD030538), Principal Investigators Leo Cheng (University of Auckland) and Zhongming Liu (University of Michigan) 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.

Ghrelin receptor in GtoPdb v.2023.1

The ghrelin receptor (nomenclature as agreed by the NC-IUPHAR Subcommittee for the Ghrelin receptor [19]) is activated by a 28 amino-acid peptide originally isolated from rat stomach, where it is cleaved from a 117 amino-acid precursor (GHRL, Q9UBU3). The human gene encoding the precursor peptide has 83% sequence homology to rat prepro-ghrelin, although the mature peptides from rat and human differ by only two amino acids [75]. Alternative splicing results in the formation of a second peptide, [des-Gln14]ghrelin with equipotent biological activity [50]. A unique post-translational modification (octanoylation of Ser3, catalysed by ghrelin Ο-acyltransferase (MBOAT4, Q96T53) [134] occurs in both peptides, essential for full activity in binding to ghrelin receptors in the hypothalamus and pituitary, and for the release of growth hormone from the pituitary [59]. Structure activity studies showed the first five N-terminal amino acids to be the minimum required for binding [4], and receptor mutagenesis has indicated overlap of the ghrelin binding site with those for small molecule agonists and allosteric modulators of ghrelin function [45]. An endogenous antagonist and inverse agonist called Liver enriched antimicrobial peptide 2 (Leap2), expressed primarily in hepatocytes and in enterocytes of the proximal intestine [36, 69] inhibits ghrelin receptor-induced GH secretion and food intake [36]. The secretion of Leap2 and ghrelin is inversely regulated under various metabolic conditions [72]. In cell systems, the ghrelin receptor is constitutively active [46], but this is abolished by a naturally occurring mutation (A204E) that results in decreased cell surface receptor expression and is associated with familial short stature [94].

Astragaloside IV-mediated inhibition of oxidative stress by upregulation of ghrelin in type 2 diabetes-induced cognitive impairment.

This study is to observe the upregulation effect of astragaloside IV on ghrelin in diabetic cognitive impairment (DCI) rats and to investigate the pathway in prevention and treatment by reducing oxidative stress. The DCI model was induced with streptozotocin (STZ) in conjunction with a high-fat and high-sugar diet and divided into three groups: model, low-dose (40mg/kg), and high-dose (80mg/kg) astragaloside IV. After 30days of gavage, the learning and memory abilities of rats, as well as their body weight and blood glucose levels, were tested using the Morris water mazeand then detection of insulin resistance, SOD activity, and serum MDA levels. The whole brain of rats was sampled for hematoxylin-eosin and Nissl staining to observe pathological changes in the hippocampal CA1 region. Immunohistochemistry was used to detect ghrelin expression in the hippocampal CA1 region. A Western blot was used to determine changes in GHS-R1α/AMPK/PGC-1α/UCP2. RT-qPCR was used to determine the levels of ghrelin mRNA. Astragaloside IV reduced nerve damage, increased superoxide dismutase (SOD) activity, decreased MDA levels, and improved insulin resistance. Ghrelin levels and expression increased in serum and hippocampal tissues, and ghrelin mRNA levels increased in rat stomach tissues. According to Western blot, it increased the expression of the ghrelin receptor GHS-R1α and upregulated the mitochondrial function associated-protein AMPK-PGC-1α-UCP2. Astragaloside IV increases ghrelin expression in the brain to reduce oxidative stress and delay diabetes-induced cognitive impairment. It may be related to the promotion of ghrelin mRNA levels.

Development of apigenin loaded gastroretentive microsponge for the targeting of Helicobacter pylori

The goal of the present work was to invent an apigenin-stacked gastroretentive microsponge to target H. pylori. The quasi-emulsion technique was used to prepare microsponges, which were then tested for various physicochemical properties, in-vivo gastric retention, and in-vitro anti-H. pylori study. The microsponge that demonstrated a comparatively good product yield (76.23 ± 0.84), excellent entrapment efficiency (97.84 ± 0.85), sustained in-vitro gastric retention period, and prolonged drug release were chosen for further investigations. The microsponge's SEM analysis showed that it had a spherical form, porous surface, and interconnected spaces. No drug-polymer interactions were detected in the FTIR investigation. Apigenin was found to be dispersed in the microsponge's polymeric matrix according to DSC & XRD investigations. Moreover, the microsponge in the rat's stomach floated for 4 h, according to the ultrasonography. The antibacterial activity of apigenin against H. pylori was nearly two folds more than the pure apigenin and had a more sustained release in the best microsponge, according to the in vitro MIC data, when compared to pure apigenin. To sum up, the developed gastroretentive microsponge with apigenin offers a viable alternative for the efficient targeting of H. pylori. But more preclinical & clinical studies of our best microsponge would yield considerably more fruitful results.

Mechanokinetics of the spontaneous contractions of smooth muscles in the stomach and large intestine of rats under chronic effect of ТiО2 nanoparticles

Background. Currently, nano-sized materials of titanium dioxide (TiО2) have wide industrial uses, particularly in the food industry and pharmacology. Therefore, the problem of TiО2 toxicity to living organisms in case of their chronic in vivo intake needs thorough investigation. As nanoparticles enter the internal environment of the body, they spread with the bloodstream to tissues and organs, where they partially accumulate. Thus studying the state of the pacemaker mechanisms of regulation of smooth muscle spontaneous contractions in the stomach and large intestine under chronic exposure to TiО2 nanoparticles is relevant and interesting. The purpose of this research work was to study the spontaneous contractile activity of the gastric and large intestine smooth muscles of rats under chronic (for 6 months) intake of an aqueous suspension of TiО2 nanoparticles. Materials and Methods. Wistar rats were used in the experiments. Rats of the experimental group were daily intragastrically administered an aqueous suspension of ТіО2 nanoparticles for six months at a dose of 0.1 mg/kg. The study of the mechanokinetics of the contraction-relaxation process of muscle preparations was carried out according to the method (Kosterin et al., 2021) with the calculation of the mechanokinetic parameters of the contraction-relaxation cycle: force (Fmax, FC and FR), time (τ0, τC and τR), impulse (Іmax, ІC and ІR) and velocity (VC and VR). Results. A comprehensive mechanokinetic analysis of spontaneous contractions of the antrum and caecum circular smooth muscles was carried out in control and under chronic in vivo exposure to ТіО2 nanocolloids (0.1 mg/kg/day) for 6 months. It was found that the chronic action of ТіО2 nanocolloids significantly inhibits the contractile activity of the antrum smooth muscles accompanied by a decrease in all mechanokinetic parameters of time, force, velocity and impulse. Under the same conditions, inhibition of the spontaneous contractions of the large intestine smooth muscles was observed. However, the time (τ0, τC and τR) and impulse (Іmax, ІC and ІR) parameters increased for these muscles against the background of the decrease in the force and velocity mechanokinetic parameters. Conclusions. Modulation of the mechanokinetic parameters of the spontaneous contractile activity of the stomach and large intestine smooth muscles of rats under chronic intragastric administration of ТіО2 nanocolloids suggests that the functioning of pacemakers changes significantly under these conditions. Since the parameters of the contraction and relaxation phases of both the stomach and the large intestine smooth muscles do not differ by the magnitude of the inhibitory effects, it can be assumed that the effects of ТіО2 are not specific for particular Са2+ transport systems involved in contractile responses.

Effects of Alpinia Officinarum and Euodia Rutaecarpa on the expression of TRPA1 and TRPM8 in rats with irritable bowel syndrome

ObjectiveAlpinia Officinarum and Euodia Rutaecarpap are two traditional Chinese herbs with warm nature, usually called interior-warming medicinal and widely used to treat cold syndrome for a long history. The purpose of this study is to explore the effects of Alpinia Officinarum and Euodia Rutaecarpap on irritable bowel syndrome (IBS) rats with spleen-stomach deficiency cold syndrome, and to clarify the link between “warming the middle to alleviate pain” and transient receptor potential channel A1 (TRPA1), M8 (TRPM8). MethodsIBS rat model with spleen-stomach deficiency cold syndrome was established by cold diarrhea and restraint stress. Rats were randomly divided into the normal group, model group, positive group (pinaverium bromide), Alpinia Officinarum group and Euodia Rutaecarpa group. After continuous modeling and administration for seven days, body weight, loose stool grades, activity of ATP enzyme, pathological morphology of gastrointestinal tissue were evaluated. The expression of TRPA1 and TRPM8 in spinal ganglion, stomach and colon tissue of rats were detected by RT-PCR and immunohistochemistry. ResultsThe IBS model with spleen-stomach deficiency cold syndrome caused increase in the number of diarrhea and loss in the body weight in rats. Compared with the normal group, the loose stool grades of model group was significantly increased (P<0.01), Na+-K+-ATP and Ca2+-Mg2+-ATP activity of erythrocyte membrane were significantly decreased (P<0.01). However, compared with the model group, Alpinia Officinarum and Euodia Rutaecarpa obviously reduced the loose stool grades (P<0.05 or P<0.01), and obviously increased the activity of Na+-K+-ATP and Ca2+-Mg2+-ATP (P<0.05). The expression of TRPA1 and TRPM8 in spinal ganglia and colon tissue of the model group was markedly enhanced (P<0.01), but Alpinia Officinarum and Euodia Rutaecarpa significantly inhibited these overexpression. ConclusionThe effect of interior-warming and alleviating pain of Alpinia Officinarum and Euodia Rutaecarpa on IBS model may be mainly achieved by regulating the abnormal expression of TRPA1 and TRPM8. Thus, these results could support the fact that interior-warming medicinal such as Alpinia Officinarum and Euodia Rutaecarpa are traditionally used to cure spleen-stomach deficiency cold syndrome.

Effects of Ethanol Extract of Green Algae (Ulva lactuca L) on Histological Description, COX-1 Expression and COX-2 in Ethanol-Induced Rat’s Gastric

Ethanol is the cause of gastric ulcers by reducing the production of prostaglandins (PG) and is closely related to the enzyme cyclooxygenase. One of the plants that has been studied as a gastroprotector is the green algae Ulva lactuca L. The objectives of this research were to study the effects of Ethanol Extract of Green Algae (Ekstrak Etanol Ganggang Hijau / EEGH) Ulva lactuca L. on the histological pictures of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) expression in ethanol-induced gastric ulcer model rats. EEGH is macerated with 96% ethanol. A total of 36 rats were divided into 6 groups with 6 rats in each group. Group I and II were given food and drink, group III was given ranitidine (15.75mg/kgBW). Groups IV, V and VI were given EEGH at doses of 125, 250 and 500mg/kgBW orally. Treatments are given for 14 days. On day 14 the rats were induced with ethanol (except group I) then fasted for 24 hours and then operated on. Gastric histopathology was observed with Hematoxyclin Eosin (HE) staining to see the ability of protection against the stomach of ethanol-induced rats. Gastric protection mechanism was observed by immunohistochemically COX-1 and COX-2 expressions. The results showed that EEGH at doses of 500mg/kgBW had a protective effect as seen from a decrease in the ulcer index and a reduction in necrosis, edema, and hemorrhage. EEGH Ulva lactuca L. were given at a dose of 500mg/KgBW was able to significantly increase the percentage of COX-1 expression in glandular cells but was not able to significantly reduce COX-2 expression.

Bletilla striata Polysaccharide Nanoparticles Improved the Therapeutic Efficacy of Omeprazole on the Rat Gastric Ulcer Induced by Ethanol.

Gastric ulcers are a common clinical presentation affecting anyone, regardless of their age or gender. Nanoparticles (NPs) containing Bletilla striata polysaccharide (BSP) and omeprazole (OME) were investigated in the study for their therapeutic effect on gastric ulcers. Ethanol-induced gastric ulcers in rats (240 ± 30 g) were established. Our OME-BSP NPs were more stable than free OME in the acidic environment and can increase the absorption of OME in rat stomach, which was confirmed by in situ gastric absorption and distribution experiments. The extended blood circulation of OME-BSP NPs was also observed in rats with gastric ulcer. More importantly, OME-BSP NPs not only decreased the area of gastric ulcer and inhibited gastric acid secretion but also reversed gastric tissue damage and cell apoptosis, as revealed by HE and TUNEL staining. Subsequent SOD, MDA, PGE2, IL-6, and TNF-α tests further verified the superiority of OME-BSP NPs against rat gastric ulcer, which properly originated from superior antioxidant and anti-inflammatory effects. As a result, our OME-BSP NPs' drug delivery system improved the stability and absorption of OME in the rat stomach and achieved targeted treatment of gastric ulcers.