Rat Stomach Research Articles

Identification of glucagon like peptide-1 (GLP-1) in mice stomach

Glucagon like peptide-1 (GLP-1) is a peptide hormone encoded by the pre-proglucagon gene that serves multiple physiological functions, including incretin action. While GLP-1 is primarily synthesized in the L cells of the lower intestine, recent findings indicate its presence in the stomachs of both rats and humans. However, the role of gastric GLP-1 in other species remains unclear. In this study, we aimed to identify GLP-1-producing cells and examine the localization of GLP-1 production in the mouse stomach. We found that pre-proglucagon mRNA was higher in the corpus than that in the antrum of the stomach. In addition, GLP-1 immunoreactive cells were found in the gastric mucosa, and their cell number was higher in the corpus than that in the antrum. Double immunofluorescence showed that some GLP-1 immunoreactive cells displayed somatostatin immunoreactivity, whereas did not co-localize with ghrelin and gastrin. Moreover, transmembrane G protein-coupled Receptor 5 (TGR5) agonist decreased pre-proglucagon mRNA expression in SG-1 cells in a concentration-dependent manner, and in vivo experiments showed a decrease in its mRNA levels in the gastric corpus but not in the antrum. This study marks the first report of GLP-1 production in the mouse stomach. Our findings suggest that gastric pre-proglucagon mRNA expression is regulated by a distinct mechanism compared to the L cells of the lower intestine.

Effects of the protective and therapeutic effect of yogurt enriched with Citrus sinensis essential oil against ibuprofen-induced gastric ulcer in elderly rats.

The aim of this study was to evaluate the effect of Citrus sinensis essential oil (EO) on the proximate composition of yogurt over a 28-day shelf life and to investigate the therapeutic and prophylactic effects of functional yogurt on ibuprofen-induced gastric ulcers in a rat model. It was observed that the yogurt group containing C. sinensis EO had higher acidity, total solids, and ash values. Histologic evaluation of the stomachs of rats with gastric ulcers revealed that rats fed with functional yogurt had fewer lesions compared to the control group. The treatment group had fewer lesions than the positive control (p>0.05). Lesions in the glandular mucosa of the prophylactic group were significantly lower than those in the positive control group (p<0.05). Yogurt with C. sinensis EO may be beneficial in reducing the severity of ulcers and improving overall health.

Gastroprotective effect of rhodanine and 2,4-thiazolidinediones scaffolds in rat stomachs by contribution of anti-apoptotic (BCL-2) and tumor suppressor (P53) proteins

In recent times, the methods used to evaluate gastric ulcer healing worldwide have been based on visual examinations and estimating ulcer dimensions in experimental animals. In this study, the protective effect of rhodanine and 2,4-thiazolidinediones scaffolds compared to esomeprazole was investigated in an ethanol model of stomach ulcers in rats. Pretreatment with experimental treatments or esomeprazole prevented the development of ethanol-induced gastric ulcers. The severity of the lesions and injuries was significantly lower than that of vehicle (10% Tween 80) treated rats. Significant and excellent results were obtained with the compound 6 group, with inhibition percentage and ulcer area values of 97.8% and 12.8 ± 1.1 mm2, respectively. Synthesized compounds 2, 7 and 8 exhibited inhibition percentages and ulcer areas of 94.3% and 31.2 ± 1.1 mm2, 91. 3% and 48.1 ± 0. 8 mm2, 89. 5% and 57. 6 ± 1. 2 mm2, and 89. 1% and 60.3 ± 0. 8 mm2, respectively. These biological outcomes are consistent with the docking studies in which Compounds 7 and 8 showed remarkable binding site affinities toward human H+/K+-ATPase α protein (ID: P20648), rat H+/K+-ATPase α protein (ID: P09626), and Na+/K+-ATPase crystal structure (PDB ID:2ZXE) with binding site energies of − 10.7, − 9.0, and − 10.4 (kcal/mol) and − 8.7, − 8.5, and − 8.0 (kcal/mol), respectively. These results indicate that these test samples were as effective as esomeprazole. Likewise, immunohistochemical staining of antiapoptotic (BCL2) and tumor suppressor (P53) proteins showed strong positive marks in the10% Tween 80- treated group, opposing the mild staining results for the esomeprazole-treated group. Similarly, the staining intensity of the group treated with Compounds 2–8 was variable for both proteins.

Comparative Study on the Gross Anatomy of Some Abdominal Organs in Albino Rat (Rattus norvegicus) and Albino Mouse (Mus musculus)

A comparative gross anatomical study was carried out on six apparently healthy adult male albino rats (Rattus norvegicus) and albino mice (Mus musculus) (Three rats and three mice) The aim of the current work is to demonstrate the gross anatomical topography, morphology and fixation of (liver, kidney, spleen, stomach and pancreas) in order to highlight similarities and differences between both species. The animals were brought from local animal markets and delivered to the anatomy laboratory of the Faculty of Veterinary Medicine Cairo University, Egypt. After euthanasia, animals were anatomically dissected via mid laparotomy to study the concerned abdominal viscera in both species. The organs were removed separately and preserved by both freezing and immersion in a container filled with 10% neutral buffered formalin solution for further examination. Photographs of the organs insitu and isolated were taken, discussed and compared with that of the other lab mammals in previous literatures. The study confirmed the absence of the gall bladder and the round ligament of liver in albino rat, while the hepatorenal ligament was absent in albino mouse. Also, the site of renal impression was found to be located on the right lateral hepatic lobe in albino rat while on the caudate process of liver in the albino mouse. Albino rats and mice had a bean shaped smooth unipapillated kidneys, however the position of kidneys greatly varied between both species. The characteristic crescentic-shaped stomach in rats with a tightly closed esophageal opening compared to the thumb-shaped stomach of mice with slightly loose esophageal opening were anatomical remarks. The proper knowledge of the normal morphology and topography of these abdominal viscera would assist veterinarians in designing of therapeutic surgical approaches in abdominal cavity and experimental transplantations.

Synergistic gastroprotective and antioxidative effects of natural olive oil and usnic acid isolated from Usnea longissima, a lichen species in Anatolia (Türkiye), in the indomethacin ulcer model created in rats

Usnea longissima, a medically important lichen growing up in forests in Anatolia (Turkey). In this study, the gastroprotective effect of usnic acid (UA) was investigated using an indomethacin (IND)-induced gastric ulcer model in rats. While 25, 50, 100 and 200 mg/kg UA doses were dissolved in 2 ml of olive oil (OO) and administered to rats, only OO was given to one group. In addition, lansoprazole (LAN) and ranitidine (RAN) and IND were dissolved in water and administered to rat groups. IND administration caused very high levels of damage to rat stomachs. On the other hand, when four doses of UA, OO, RAN and LAN were administered, it was determined that hyperemias in the stomach of rats was significantly reduced. After macroscopic analysis of gastric tissues, the activities of superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO) and nitric oxide synthase (iNOS and cNOS) enzymes as well as glutathione (GSH) and lipid peroxidation (LPO) levels were determined in these tissues. After IND application, it was detected increases in MPO, CAT and iNOS activities in gastric tissues and decreases in SOD, cNOS and GSH amounts. Four doses of UA, OO, RAN and LAN applications reversed the trend, bringing them closer to healthy levels.

Electrophysiology, molecular modelling, and functional analysis of the effects of dietary quercetin and flavonoid analogues on Kir6.1 channels in rat stomach fundus smooth muscle

Flavonoids, ubiquitously distributed in the plant world, are regularly ingested with diets rich in fruit, vegetables, wine, and tea. During digestion, they are partially absorbed in the stomach. The present work aimed to assess the in vitro effects of quercetin and ten structurally related flavonoids on the rat gastric fundus smooth muscle, focussing on ATP-dependent K+ (Kir6.1) channels, which play a central role in the regulation of resting membrane potential, membrane excitability and, consequently, of gastric motility. Whole-cell currents through Kir6.1 channels (IKir6.1) were recorded with the patch-clamp technique and the mechanical activity of gastric fundus smooth muscle strips was studied under isometric conditions. Galangin ≈ tamarixetin > quercetin > kaempferol > isorhamnetin ≈ luteolin ≈ fisetin > (±)-taxifolin inhibited pinacidil-evoked, glibenclamide-sensitive IKir6.1 in a concentration-dependent manner. Morin, rutin, and myricetin were ineffective. The steric hindrance of the molecule and the number and position of hydroxyl groups on the B ring played an important role in the activity of the molecule. Molecular docking simulations revealed a possible binding site for flavonoids in the C-terminal domain of the Kir6.1 channel subunit SUR2B, in a flexible loop formed by residues 251 to 254 of chains C and D. Galangin and tamarixetin, but not rutin relaxed both high K+- and carbachol-induced contraction of fundus strips in a concentration-dependent manner. Furthermore, both flavonoids shifted to the right the concentration-relaxation curves to either pinacidil or L-cysteine constructed in strips pre-contracted by high K+, rutin being ineffective. In conclusion, IKir6.1 inhibition exerted by dietary flavonoids might counterbalance their myorelaxant activity, affect gastric accommodation or, at least, some stages of digestion.

The Effect of Avocado Leaf Ethanol Extract (Persea Americana Mill) on Aspirin-Induced Reduction of Gastric Acid in Rats

Gastritis is inflammation of the mucosal lining of the stomach. Gastritis can be caused by several things, one of which is the use of anti-inflammatory drugs which can damage the gastric mucosal lining which occurs in two ways, namely local and systemic. Local damage is caused by being lipophilic and acidic, while systemic damage is caused by a significant decrease in prostaglandin production. Avocado leaf ethanol extract contains flavonoids and saponins which have anti-inflammatory effects and inhibit histamine secretion. This study aims to analyze the activity of ethanol extract of avocado leaves in reducing gastritis in vivo in rats induced by apirin. Samples of 60 mice weighing 150-200 g were divided into 5 groups, namely negative control group (CMC Na), positive control (Simetidine), ethanol extract of avocado leaves 100, 200, 400 mg/Kg BW. Mice were fasted for 24 hours, induced by aspirin 400 mg/KgBW for 24 hours and mice remained fasted. then given treatment according to group division for 8 days. Every 2 days after treatment, 3 mice were taken from each group to be sacrificed by dislocation, the mice's stomachs were dissected, all gastric fluid was collected and the stomach contents were removed and then washed with 0.9% NaCl solution. Gastric fluid is used to check fluid concentration and pH. Then the rat's stomach was opened by stretching it to count the number of ulcers and the ulcer index that occurred. The results of the study showed that the 400 mg/KgBW avocado leaf ethanol extract group had an anti-inflammatory effect that was almost the same as Cimetidine, this was shown by the results of decreasing gastric fluid concentration, decreasing the number of ulcers, decreasing the ulcer index and increasing gastric pH. Based on the description above, it can be concluded that the ethanol extract of avocado leaves has an anti-inflammatory effect in reducing gastritis.

Nanopore sequencing of metagenomic DNA from rat stomach contents to infer diet

Nanopore sequencing of metagenomic DNA from rat stomach contents to infer diet

Trace Metal Accumulation in Rats Exposed to Mine Waters: A Case Study, Bor Area (Serbia).

Zinc (Zn), copper (Cu), iron (Fe), manganese (Mn), cadmium (Cd), and lead (Pb) levels were measured in the Bor City water supply system (control) and two watercourses exposed to mining wastewaters, i.e., the Lutarica River (one site) and the Kriveljska River (two sites). The same parameters were determined in the brain, heart, lungs, stomach, liver, spleen, kidneys, and testes of male Wistar rats given water from these sources for 2 months. Water Cu, Fe, Cd, and Pb were outside the safe range, excepting the reference site. Significant impacts on intra-organ metal homeostasis were detected, especially in the brain, stomach, kidneys, and testes. The dynamics and magnitude of these changes (versus controls) depended on the target organ, analyzed metal, and water origin. The greatest number of significant intra-organ associations between essential and non-essential metals were found for Cd-Zn, Cd-Cu, and Cd-Mn. A regression analysis suggested the kidneys as the most relevant organ for monitoring water manganese, and the stomach and brain for lead. These results highlight the environmental risks associated with mining wastewaters from the Bor area and could help scientists in mapping the spatial distribution and severity of trace metal contamination in water sources.

Effects of green decorated AgNPs on lignin-modified magnetic nanoparticles mediated by Cydonia on cecal ligation and puncture-induced sepsis

Abstract Sepsis is a common and deadly syndrome that despite all the progress in its control, the death rate caused by it is high. Sepsis is a serious problem that needs immediate attention and treatment. This infection, especially if it is caused by bacteria resistant to several drugs, causes high mortality. About two-thirds of sepsis cases occur in hospitalized patients. Several factors such as increasing the age of the population, increasing the duration of chronic diseases, high consumption of antibiotics and corticosteroids, use of mechanical devices and intravascular devices play a role in increasing its incidence. We herein demonstrate the biogenic procedure for the in situ immobilizing gold nanoparticles over lignin (Lig)-modified Fe3O4 magnetic nanoparticles mediated by Cydonia leaf extract (Fe3O4@Lig-Ag NPs) and its catalytic activity on the acetylation of alcohols using acetic anhydride and subsequent biological performances. The successful synthesis of Fe3O4@Lig-Ag NPs was assessed using an array of advanced techniques like field emission scanning electron microscopy, fourier transformed infrared spectroscopy, transmission electron microscopy EDX, elemental mapping, vibrating-sample magnetometer, and X-ray diffraction. Cecal ligation and puncture was used for inducing the sepsis model in rats. Several doses of Fe3O4@Lig-Ag NPs (45, 15, and 5 µg/kg) on oxidant–antioxidant, inflammatory mediators mRNA such as IL-1 and TNF-α, and its effects on the levels of expression were assessed in the kidney, liver, duodenum, lung, and stomach. When septic rats kidney, liver, duodenum, lung, and stomach were compared with those of the control group, it was found that Fe3O4@Lig-Ag NPs dose-dependent administration raised glutathione levels and superoxide dismutase activity and significantly reduced the levels of malondialdehyde. The Fe3O4@Lig-Ag NPs (45 µg/kg) indicated greater anti-oxidative effects than the 5 and 15 µg/kg doses for all the assessed parameters. In addition, the expression of TNF-α mRNA in the CLP + 45 µg/kg group was decreased in comparison with the control group. Fe3O4@Lig-Ag NPs reduced oxidative stress by enhancing the free radicals scavenging effects and supporting endogenous antioxidants. The Fe3O4@Lig-Ag NPs potent antioxidant property may be related to the cytokine cascade suppression during sepsis. The above findings offer that Fe3O4@Lig-Ag NPs administration may indicate a modern treatment for the inhibition of liver, kidney, lung, duodenum, and stomach tissues damage caused by septic conditions.

Characterization of neuromuscular transmission and projections of muscle motor neurons in the rat stomach.

The stomach is the primary reservoir of the gastrointestinal tract, where ingested content is broken down into small particles. Coordinated relaxation and contraction is essential for rhythmic motility and digestion, but how the muscle motor innervation is organized to provide appropriate graded regional control is not established. In this study, we recorded neuromuscular transmission to the circular muscle using intracellular microelectrodes to investigate the spread of the influence of intrinsic motor neurons. In addition, microanatomical investigations of neuronal projections and pharmacological analysis were conducted to investigate neuromuscular relationships. We found that inhibitory neurotransmission to the circular muscle is graded with stimulus strength and circumferential distance from the stimulation site. The influence of inhibitory neurons declined between 1 and 11 mm from the stimulation site. In the antrum, corpus, and fundus, the declines at 11 mm were about 20%, 30%, and 50%, respectively. Stimulation of inhibitory neurons elicited biphasic hyperpolarizing potentials often followed by prolonged depolarizing events in the distal stomach, but only hyperpolarizing events in the proximal stomach. Excitatory neurotransmission influence varied greatly between proximal stomach, where depolarizing events occurred, and distal stomach, where no direct electrical effects in the muscle were observed. Structural studies using microlesion surgeries confirmed a dominant circumferential projection. We conclude that motor neuron influences extend around the gastric circumference, that the effectiveness can be graded by the recruitment of different numbers of motor neuron nerve terminals to finely control gastric motility, and that the ways in which the neurons influence the muscle differ between anatomical regions.NEW & NOTEWORTHY This study provides a detailed mapping of nerve transmission to the circular muscle of the different anatomical regions of rat stomach. It shows that excitatory and inhibitory influences extend around the gastric circumference and that there is a summation of neural influence that allows for finely graded control of muscle tension and length. Nerve-mediated electrical events are qualitatively and quantitatively different between regions, for example, excitatory neurons have direct effects on fundus but not antral muscle.

Effectiveness of neutral honey as a tissue fixative in histopathology.

Background: In routine histopathology, 10% neutral buffered formalin (NBF) is the choice fixative. However, formalin is a human carcinogen, so there is a necessity for a safer alternative. To the best of our knowledge, neutral honey, not natural or artificial honey, has not been tested to fix histological samples. This study determined the effectiveness of neutral buffered honey and other types of fixatives to fix histological tissues. Methods: The study was conducted between July 2019 and August 2020 at Sultan Qaboos University, Oman. Sections from three rat livers, kidneys, and stomach tissues were fixed with 10% NBF, neutral buffered Sumer honey, neutral buffered date honey, formalin, Sumer honey, date honey, alcoholic formalin, alcoholic Sumer honey, and alcoholic date honey for 24 hours. Samples were stained with hematoxylin and eosin (H&E), special stains, and vimentin methods. Three expert biomedical scientists then evaluated the fixed and stained samples for the quality of all sections. The fixation ability of the different honey solutions was then compared to 10% NBF and the utility was determined using nuclear and cytoplasmic criteria, specificity, and intensity. Results: H&E showed adequate staining in all groups compared to 10% NBF. The specificity and intensity of all groups for the Periodic acid-Schiff method were identical to 10% NBF except for Sumer honey and alcoholic date honey. Vimentin showed comparable findings with 10% NBF as there were no significant differences. Conclusions: The findings of this study encourage the use of honey, including neutral, as a possible safe substitute fixative for formalin, however, further experiments on larger specimens should be conducted.

Spinal afferent innervation in flat-mounts of the rat stomach: anterograde tracing

The dorsal root ganglia (DRG) project spinal afferent axons to the stomach. However, the distribution and morphology of spinal afferent axons in the stomach have not been well characterized. In this study, we used a combination of state-of-the-art techniques, including anterograde tracer injection into the left DRG T7-T11, avidin–biotin and Cuprolinic Blue labeling, Zeiss M2 Imager, and Neurolucida to characterize spinal afferent axons in flat-mounts of the whole rat stomach muscular wall. We found that spinal afferent axons innervated all regions with a variety of distinct terminal structures innervating different gastric targets: (1) The ganglionic type: some axons formed varicose contacts with individual neurons within myenteric ganglia. (2) The muscle type: most axons ran in parallel with the longitudinal and circular muscles and expressed spherical varicosities. Complex terminal structures were observed within the circular muscle layer. (3) The ganglia-muscle mixed type: some individual varicose axons innervated both myenteric neurons and the circular muscle, exhibiting polymorphic terminal structures. (4) The vascular type: individual varicose axons ran along the blood vessels and occasionally traversed the vessel wall. This work provides a foundation for future topographical anatomical and functional mapping of spinal afferent axon innervation of the stomach under normal and pathophysiological conditions.

SIMILARITIES BETWEEN MORPHOLOGICAL INDICATORS OF THE STOMACH OF HUMANS AND WHITE-BREEDLESS RATS

. Information about the anatomy of the stomach of white-breedless rats is very rare in the scientific literature. The shape, structure, and topography of rat stomachs are significantly different from those of vertebrates, but the same sections as shark stomachs can be found in them. This structure of white rat stomach sections characterizes the sac-like formation of the digestive tract. In the anterior part of the abdominal cavity of rats, on the left side of the midline, there is a hole for the heart between the esophagus and the line of the lesser curvature of the stomach. The liver is located in the small curvature of the stomach and partially covers it. The greater curvature of the stomach touches the caecum and cecum.

Histological Structure of Male Wistar Rats’ Stomach Fed with Yam Tuber Flour Supplementation

A residential rat might harm human health because it acts as a disease reservoir. It has been many efforts to control this rate using synthetic rodenticide. Nevertheless, synthetic rodenticides broke the environment and made rats resistant. Yam (Dioscorea hispida) tube application on rat’s bite could solve the problem. This study evaluated the histology of male Wistar rats (Rattus norvegicus) fed with bite block supplemented with different yam tuber flour concertation to control residential rat populations. Five different treatments were applied with five replications. The treatments were negative control and brodifacoum 0.005% (positive control), 30%, 50%, and 70% of yam tuber flour. The results show that yam tuber supplementation caused damage to male Wistar rat stomachs, as indicated by mucosal erosion and the presence of inflammatory cells. The statistical test indicated that stomach damage significantly differed among treatments, with the severest damages caused by 50% yam tuber supplementation. It could be concluded that the rat’s bite containing yam tuber flour caused stomach damage, and the feed bite containing 70% yam tuber flour was the most effective. This result proved that yam tuber has good potential as a natural rodenticide to control residential rat populations.

Пропіонова кислота відновлює секрецію муцину у шлунку при експериментальному цукровому діабеті

Type 2 diabetes mellitus (T2DM) is associated with a number of complications, in particular, gastrointestinal tract dysfunction. Impaired mucin secretion by the gastric mucosa in rats with T2DM may affect the absorption of drugs in the stomach and may explain the poor efficacy of treatment and correction of the condition. The aim of our work was to study changes in mucin secretion by the mucous membrane of the gastric fundus in rats with T2DM and the administration of metformin in combination with propionate. T2DM was modelled in rats by a high-fat diet for 3 months with a single administration of streptozotocin (25 mg/kg). Pharmacological correction was performed by intragastric administration of metformin (60 mg/ kg), propionate (60 mg/kg), and combined administration of the mentioned drugs for 14 days. Structural changes in the gastric mucosa and mucopolysaccharide secretion activity were assessed by histochemistry. Western blot analysis of MUC5AC expression was performed. A significant decrease in mucin production was observed in the lower stomach of rats, which was associated with a decrease in the density of cells actively producing acidic mucopolysaccharides. Metformin administration to animals with T2DM did not restore mucin production in the gastric fundus, whereas propionate administration increased acid mucopolysaccharide secretion. An increase in the neutral component of mucus and MUC5AC was found in T2DM. The combined administration of metformin and propionate helped to reduce the content of this mucin. The identified morphofunctional changes in the gastric fundus require further research and should be taken into account when using oral hypoglycaemic drugs because the loss of the mucin barrier layer may affect the state of the gastric mucosa and the absorption of drugs.

Some Anatomical and Histological effects of Diclofenac Sodium to the Stomach, Kidney and Liver in rats.

Diclofenac sodium (DS) is one of Non-steroidal anti-inflammatory drugs (NSAIDs).It is commonly used to relief pain and treats several disorders like renal diseases, inflammation and fever. This study was designed to show the effects of over dose of diclofenac sodium75ml/kg B.W in 5 days anatomically and histologically to the stomach, kidney and liver. 24 experimental rats were used,femal ages range between 8-10 weeks. The anatomical change include increase weight and grossly change in surface of these organs and mucosa of stomach but histological change in these tissue include damages which can form mucosal erosions in stomach. However, in kidney it causes infraction in the same area of cortex. Moreover, medulla causes congestion, and in liver occur hepatocyte inflammation and increase fibrous tissue.

A comparative metabolomics study between grain-sized moxibustion and suspended moxibustion on rats with gastric ulcers

Grain-sized moxibustion (GS-Moxi) and suspended moxibustion (S-Moxi) represent the two typical local heat therapies in Traditional Chinese Medicine (TCM) and have been extensively used in treating gastric ulcers (GU) in China. However, the difference in biological response between the two moxibustion therapies in treating GU remains unclear. Here we investigated the therapeutic effect and potential mechanistic difference underlying the two moxibustion methods. Ethanol-induced GU model was established and was treated with GS-Moxi or S-Moxi at ST36 and ST21 for 5 days separately. And then, gastric histopathological examination, immunohistochemical staining for repair factors (EGFR, VEGF, Ki67), and 1H NMR-based metabolomics analysis of plasma and stomach of rats were conducted. We found GS-Moxi and S-Moxi effectively alleviated gastric damage and significantly increased the expression of related repair factors. However, S-Moxi corrected aberrant energy metabolism and lipids metabolism in GU rats but had little effect on neurotransmitter-related metabolism, while GS-Moxi regulated energy metabolism and neurotransmitter-related metabolism in GU rats but had no effect on lipids metabolism. We further proposed that the main target of S-Moxi may be liver and vasculature, whereas GS-Moxi specially targeted the stomach via regulating nervous system. This study strongly verified the outstanding gastroprotective effects of moxibustion and enriched our understanding of the varied biological responses triggered by different moxibustion methods.

Protective effect of Lizhong Pill on nonsteroidal anti-inflammatory drug-induced gastric mucosal injury in rats: Possible involvement of TNF and IL-17 signaling pathways

Ethnopharmacological relevanceThe traditional Chinese medicine formula Lizhong Pill (LZP) and its herbal constituents are frequently utilized in Asian (China, Saudi Arabia, India, Japan, etc.) and some European (Russia, Sweden, UK, etc.) nations to treat various gastrointestinal ailments. Aim of the studyThis study aimed to investigate the protective impact and potential mechanism of LZP against indomethacin (IND)-induced gastric mucosal injury in rats. Material and methodsUsing a biochemical kit, we investigated the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) in rat serum, as well as pepsin in rat stomach tissue, using an IND-induced rat model of gastric mucosal injury. Various imaging tools, including HE staining, scanning electron microscopy (SEM), and transmission electron microscopy (TEM), were used to examine the gastric mucosa’s surface morphology and ultrastructure. Furthermore, molecular docking was employed to predict the binding capacity of the primary bioactive components of LZP to the critical molecular protein targets in the IL-17 and TNF signaling pathways. At the same time, immunofluorescence was used to determine the protein expressions of CASP3, VCAM1, MAPK15, MMP3, IL-17RA, and TNFR1. ResultsThe present study demonstrates that LZP (3.75 and 7.50 g/kg) significantly reduces the gastric mucosal injury index induced by IND. This effect is evidenced by the improved morphology, surface, and structure of the gastric mucosa, as determined by HE, SEM, and TEM findings. Additionally, 3.75 and 7.50 g/kg LZP intervention significantly increased SOD and CAT contents and inhibited pepsin and GST activities. Molecular docking analysis revealed that the small molecular components of LZP can bind spontaneously to crucial proteins involved in the IL-17 and TNF signaling pathways, including MAPK15, MMP3, VCAM1, and CASP3. The immunofluorescence findings proved that LZP (3.75 and 7.50 g/kg) can inhibit the protein expressions of MAPK15, MMP3, VCAM1, CASP3, IL-17RA, and TNFR1. ConclusionsOur investigation findings demonstrate that LZP can potentially ameliorate IND-induced damage to the gastric mucosa by inhibiting IL-17 and TNF signaling pathways. These results offer encouraging support for using alternative medicine to manage drug-induced gastric mucosal injury.

Granule Dendrobii suppresses chronic atrophic gastritis induced by N-methyl-N'-nitro-N-nitrosoguanidine by modulating the gastrointestinal bacteria in rats.

Chronic atrophic gastritis (CAG) is an important stage in the transformation of the normal gastric mucosa into gastric cancer. Granule Dendrobii (GD), a proprietary Chinese medicine, has proven clinical efficacy in treating CAG. GD might promote the reversal of precancerous lesions by improving them in CAG patients. However, the mechanism of GD in CAG treatment is relatively less understood. Here, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced CAG rats were treated with GD and its efficacy was evaluated by observing the changes in the rats' weight and the pathology of gastric tissues. The potential effect of GD on the bacteria was predicted and verified in the large and small intestines and stomachs of CAG rats using amplicon sequencing and RT-qPCR. The results showed that GD could ameliorate the symptoms of body weight loss in CAG rats. Hematoxylin-Eosin (HE) and Alcian Blue (AB) staining showed that GD significantly improved the pathological state of the gastric mucosa in CAG rats. The relative abundance (RA) of Lactobacillus and Turicibacter significantly decreased after GD intervention compared with that of the model group (P < 0.05), indicating that GD might improve CAG by regulating the RA of Lactobacillus and Turicibacter. These findings revealed that Lactobacillus and Turicibacter as bacteria agents associated with gastritis, have the potential to inhibit gastric cancer, especially Turicibacter maybe another pathogen of CAG besides Helicobacter pylori (HP), which is worthy of further study. Meanwhile, the findings provided new ideas and materials for the research and development of new CAG drugs.