scholarly journals Hydroxyproline, a Serum Biomarker Candidate for Gastric Ulcer in Rats: A Comparison Study of Metabolic Analysis of Gastric Ulcer Models Induced by Ethanol, Stress, and Aspirin

2014 ◽  
Vol 9 ◽  
pp. BMI.S15918 ◽  
Author(s):  
Kenichiro Takeuchi ◽  
Maki Ohishi ◽  
Keiko Endo ◽  
Kenichi Suzumura ◽  
Hitoshi Naraoka ◽  
...  

Gastrointestinal symptoms are a common manifestation of adverse drug effects. Non-steroid anti-inflammatory drugs (NSAIDs) are widely prescribed drugs that induce the serious side effect of gastric mucosal ulceration. Biomarkers for these side effects have not been identified and ulcers are now only detectable by endoscopy. We previously identified five metabolites as biomarker candidates for NSAID-induced gastric ulcer using capillary electrophoresis–mass spectrometry (CE–MS)-based metabolomic analysis of serum and stomach from rats. Here, to clarify mechanism of changes and limitations of indications of biomarker candidates, we performed CE–MS-based metabolomic profiling in stomach and serum from rats with gastric ulcers induced by ethanol, stress, and aspirin. The results suggest that a decrease in hydroxyproline reflects the induction of gastric injury and may be useful in identifying gastric ulcer induced by multiple causes. While extrapolation to humans requires further study, hydroxyproline can be a new serum biomarker of gastric injury regardless of cause.

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1006 ◽  
Author(s):  
Nabil A. Alhakamy ◽  
Shaimaa M. Badr-Eldin ◽  
Osama A. A. Ahmed ◽  
Abdulrahman A. Halwani ◽  
Hibah M. Aldawsari ◽  
...  

A peptic ulcer is an alimentary tract injury that leads to a mucosal defect reaching the submucosa. This work aimed to optimize and maximize ellagic acid (EA) loading in Ca pectinate floating beads to maximize the release for 24 h. Three factors were selected: Ca pectinate concentration (X1, 1–3 w/v %), EA concentration (X2, 1–3 w/v %) and the dropping time (X3, 10–30 min). The factorial design proposed eight formulations. The optimized EA–Ca pectinate formulation was evaluated for the gastric ulcer index and the oxidative stress parameter determination of gastric mucosa. The results indicated that the optimum EA–Ca pectinate formula significantly improved the gastric ulcer index in comparison with raw EA. The protective effect of the optimized EA–Ca pectinate formula was further indicated by the histopathological features of the stomach. The results of the study indicate that an EA formulation in the form of Ca pectinate beads would be effective for protection against gastric ulcers because of Nonsteroidal anti-inflammatory drugs (NSAID) administration.


2015 ◽  
Vol 64 (4) ◽  
pp. 403-405
Author(s):  
Ancuta Ignat ◽  
◽  
Gabriela Paduraru ◽  
Angelica Cristina Marin ◽  
Anamaria Ciubara ◽  
...  

Nonsteroidal anti-inflammatory agents (NSAIDs) produce gastric lesions through two mechanisms: local irritation and systemic action. A 2 year and 10 months old female received NSAID for acute upper respiratory infection for 2 days and she developed coffee ground vomitus one day later. Upper gastrointestinal endoscopy revealed a gastric ulcer. She was negative for H. pylori infection, and she was diagnosed with NSAID – induced acute gastric ulcer in the absence of other causes of gastric ulcer. Gastric ulcers develop very rarely after a short-term administration of NSAIDs, which prompted us to report this case. Balancing the risk and the benefit of eradication therapy, it is indicated, for every patient who must follow a chronic treatment with anti-inflammatory drugs, to look for possible associated risk factors.


2021 ◽  
Vol 12 ◽  
Author(s):  
Catarina Alves de Lima Serafim ◽  
Maria Elaine Cristina Araruna ◽  
Edvaldo Balbino Alves Júnior ◽  
Leiliane Macena Oliveira Silva ◽  
Alessa Oliveira Silva ◽  
...  

Background: (-)-Carveol (p-Mentha-6,8-dien-2-ol) is a monocyclic monoterpenic alcohol, present in essential oils of plant species such as Cymbopogon giganteus, Illicium pachyphyllum and in spices such as Carum carvi (cumin). Pharmacological studies report its antitumor, antimicrobial, neuroprotective, vasorelaxant, antioxidant and anti-inflammatory activity.Hypothesis/Purpose: The objective of this study was to evaluate the acute non-clinical oral toxicity, gastroprotective activity of monoterpene (-)-Carveol in animal models and the related mechanisms of action.Methods: Acute toxicity was assessed according to OECD guide 423 in mice. Ethanol, stress, NSAIDs and pylorus ligation-induced gastric ulcer models were used to investigate antiulcer properties. The related mechanisms of action were using the ethanol-gastric lesions protocol.Results: (-)-Carveol has low toxicity, with a lethal dose 50% (LD50) equal to or greater than 2,500 mg/kg according to OECD guide nº 423. In all gastric ulcer induction methods evaluated, (-)-Carveol (25, 50, 100 and 200 mg/kg, p.o.) significantly reduced the ulcerative lesion in comparison with the respective control groups. To investigate the mechanisms involved in the gastroprotective activity, the antisecretory or neutralizing of gastric secretion, cytoprotective, antioxidant and immunoregulatory effects were evaluated. In the experimental protocol of pylorus ligation-induced gastric ulcer, (-)-Carveol (100 mg/kg) reduced (p < 0.001) the volume of gastric secretion in both routes (oral and intraduodenal). The previous administration of blockers NEM (sulfhydryl groups blocker), L-NAME (nitric oxide synthesis inhibitor), glibenclamide (KATP channel blocker) and indomethacin (cyclo-oxygenase inhibitor), significantly reduced the gastroprotection exercised by (-)-Carveol, suggesting the participation of these pathways in its gastroprotective activity. In addition, treatment with (-)-Carveol (100 mg/kg) increased (p < 0.001) mucus adhered to the gastric wall. Treatment also increased (p < 0.001) levels of reduced glutathione (GSH), superoxide dismutase (SOD) and interleukin-10 (IL-10). It also reduced (p < 0.001) malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels.Conclusion: Thus, it is possible to infer that (-)-Carveol presents gastroprotective activity related to antisecretory, cytoprotective, antioxidant and immunomodulatory mechanisms.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
A. Folorunsho Ajayi ◽  
S. Babafemi Olaleye

Cell proliferation and angiogenesis are of utmost importance for healing to take place. The KI67 and EGFR proteins are markers of cell proliferation, while CD31 and factor VIII are markers of angiogenesis. To elucidate the mechanism responsible for delayed healing of the gastric injury in old age, we analyzed the expression of these markers in rats of different months during the healing of an acetic acid-induced gastric ulcer. Male Wistar rats (aged 3, 6, 12, and 18 months) divided into four groups, according to their ages, formed the experimental animals. Stomach tissue samples were collected on days 3, 7, 14, and 21 after induction for assessment of ulcer healing. The area of gastric mucosa healed was inversely proportional to age. The expression of markers of proliferation (KI67 and EGFR) and angiogenesis (factor VIII and CD31) decreased significantly (p<0.05) in older rats when compared with younger ones (3 months > six months > 12 months > 18 months) on days 7, 14, and 21 after induction of gastric ulcer. This study revealed that the slower gastric ulcer healing rate in older rats might be due to reduced epithelial cell proliferation and angiogenic activities.


2019 ◽  
Vol 4 (5) ◽  
pp. 19-25
Author(s):  
E. V. Moroz ◽  
A. Y. Karateev ◽  
E. V. Kryukov ◽  
A. A. Sokolov ◽  
E. N. Artemkin

Intaking antithrombotic funds (ATA) and non-steroidal anti-inflammatory drugs (NSAIDs) is one of the most frequent causes of pathology in gastrointestinal (GI) tract.The purpose of the study: comparison of pathological changes of the mucous membrane in the upper GI tract, that occur against the background of ATA and NSAIDs admission.Material and methods. Endoscopic data of two groups of patients taking ATA and NSAIDS have been compared. The first group of 448 patients from the 10th Gastrointestinal Department in N.N. Burdenko Main Military Clinical Hospital was on record from 2013 to 2017. The patients had erosive ulcerous changes of gastrointestinal mucosa, occurred against the background of the ATA admission. The second group comprised 6431 patients with rheumatic diseases. They were hospitalized in the clinic of V.A. Nasonova Research Institute of Rheumatology in the period from 2007 to 2016 and took NSAIDs regularly.Results. Duodenal and gastric ulcer changes in gastric mucosa and duodenal ulcers were identified in 168 (37.5 %) patients taking ATA and in 1691 (26.3 %) patient treated with NSAIDS. Structure of pathology varied. So, against the background of ATA and NSAIDS admission, the number of acute gastric ulceration amounted to 6.5 % and 15.5 % (p < 0.001); acute ulcers duodenal was 2.9 % and 4.9 %; combined ulcerative lesions of gastric and duodenal was 2.9 % and 2.0 %; multiple erosions of gastroduodenal mucosa were 52.4 % and 15.7 % (p < 0.001); single erosion was 35. 1% and 61.6 %. The factor of ulcer history and age ≥ 65 years old increased significantly the risk of duodenal and gastric ulcer changes in patients taking ATA and NSAIDs: OR 5.182 (95% CI 2.701–9.942) and 3.24 (95% CI 2.19–5.34), 4.537 (95% CI 2.036–10.11) and 2.016 (95% CI 1.230–2.917) respectively. Intaking of proton pump inhibitor (PPI) reduced significantly the risk of complications for both ATA and NSAIDs: OR 0.329 (95% CI 0.199–0.546) and 0.317 (95% CI 0.210–0.428) respectively.Conclusion. The structure of pathology of mucous in the upper gastrointestinal tract that arose against the backdrop of ATA and NSAIDs admission is different. The first is characterized by a multiple erosion, while the second one has single acute distal gastric ulcers. The ulcerative history and advanced age of patients increase significantly the risk of complications concerning the gastroduodenal mucosa when using ATA and NSAIDs. PPI is the effective means of preventing this pathology.


2015 ◽  
Vol 11 (2) ◽  
Author(s):  
Mohammad Juffrie ◽  
Ina Rosalina ◽  
Wahyu Damayanti ◽  
Ali Djumhana ◽  
A. Ariani ◽  
...  

Hyperacidity causes gastric injury, and in severe situations, ulcer could develop. The growth factors known asthe basic fibroblast growth factor (bFGF) and the epidermal growth factor (EGF) have been recognized to promoteulcer healing. Fucoidan is extracted from a brown seaweed of Okinawa called Mozuku or Cladosiphon okamuranus.Fucoidan is effective for the healing of gastric ulcers by inducing epithelial cells to produce growth factors. The aimof this study is to explore the efficacy of fucoidan in patient who suffered by gastric ulcer. A randomized control trialdouble blind was conducted to 33 eligible samples. By using four-blocks random samples were divided into fucoidanand placebo groups. 100 mg of fucoidan was given to the fucoidan group and 100 mg of glucose was given to theplacebo group. Due to ethical reasons, for both groups were given a proton pump inhibitor. There was no differencein the age category between the fucoidan group (mean: 46.23 ± 14.8 years) and the placebo group (mean: 46.18 ± 18.4years) (p: 0.28). There was also no difference in sex between the fucoidan group (female: 10/33; male 7/33) and theplacebo group (female: 7/33; male: 9/33); p: 0.38. According to the SAKITA and MIWA criterias 32 patients fulfilledA1 which indicate active severe ulcer, and 1 patient fulfilled A2 which indicate active moderate ulcer. Most of theulcers were gastric ulcer. There was a significant improvement of the grade of ulcer in fucoidan group (94%) (16/17)compared to placebo group (37.5%) (6/16,p: 0.005). There was a significant reduction of abdominal pain after 5 daysin the fucoidan group, compared to the placebo group (p: 0.04). Vomiting tends to decrease in day 6 of the fucoidangroup however its proportion is similar with that of the placebo group (p: 0.9). Fucoidan is effective for ulcer healingand reducing ulcer symptoms.Key words : fucoidan, gastric ulcer, anti-peptic activity


2016 ◽  
Vol 2016 ◽  
pp. 1-3
Author(s):  
Nitin Vashistha ◽  
Dinesh Singhal ◽  
Gurpreet Makkar ◽  
Suneel Chakravarty ◽  
Vivek Raj

Giant gastric ulcer (GGU) is defined as an ulcer more than 3 cm in diameter. Now infrequent in clinical practice, in the pre-H2 receptor antagonist (H2RA) era, the incidence of GGU varied between 12 and 24% of all gastric ulcers. Proton pump inhibitors reportedly achieve better healing rates and symptom relief in comparison to H2RA. The GGU is associated with high incidence of serious complications such as hemorrhage. A perforated GGU though rare (<2%) offers serious challenges in management. We report one such case wherein the role of multidetector CT scan (MDCT) for diagnosis and treatment planning, surgical options for GGU perforations, and factors affecting outcome are discussed.


1994 ◽  
Vol 266 (4) ◽  
pp. G657-G664 ◽  
Author(s):  
F. J. Andrews ◽  
C. Malcontenti-Wilson ◽  
P. E. O'Brien

Leukocyte adhesion to the endothelium appears to play an important role in gastric injury. This study aimed to develop immunohistochemical staining techniques to investigate the distribution and sequence of expression of both leukocyte [lymphocyte function associated antigen 1 (LFA-1)] and endothelial [intracellular adhesion molecule 1 (ICAM-1)] adhesion molecules in the mucosa after treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). In control rats there were 803 +/- 72 LFA-1-stained cells/mm2 in the deep mucosa, 134 +/- 32 cells/mm2 in the superficial mucosa, and 6.4 +/- 1.2 ICAM-1-stained blood vessels/mm2 in the total mucosa. The number of ICAM-1-stained blood vessels in the mucosa increased significantly after 30 min of treatment with intragastric aspirin (30 mM; 25.2 +/- 7.2/mm2, P < 0.01) and indomethacin (20 mg/kg; 20.7 +/- 4.4/mm2, P < 0.01) before any appreciable mucosal damage was evident. This increase was reversed by treatment with misoprostol (100 micrograms/kg) in both aspirin- (7.6 +/- 1.7/mm2, P < 0.01) and indomethacin-treated animals (10.7 +/- 2.6/mm2, P < 0.05). There was no significant increase in LFA-1-positive cells until 60 min of NSAID treatment. We conclude that the adhesion molecules LFA-1 and ICAM-1 are expressed in the normal gastric mucosa and that the number of ICAM-1-stained blood vessels increase rapidly after NSAID treatment. This increase in ICAM-1 expression may be associated with an inhibition of prostaglandin synthesis by NSAIDs. These results provide further support for the role of early vascular changes in NSAID gastropathy.


2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Xin Chen ◽  
Lijuan Hu ◽  
Huanhuan Wu ◽  
Wei Liu ◽  
Shuhe Chen ◽  
...  

Chronic gastritis and gastric ulcers are prevalent throughout the world and are considered to be a global health problem. Modified Xiaochaihutang (MXCHT) prescription is broadly used in traditional medicine hospital for the treatment of gastritis. In order to assess the anti-Helicobacter pylori (H. pylori) effect of MXCHT, agar diffusion method in vitro and fluid dilution method for the minimal inhibitory concentration (MIC) were established. The anti-inflammatory effects were then evaluated using mouse ear edema model and rat paw edema model. The ethanol-induced gastric ulcer method was employed to verify the gastroprotective effect of active extracts in MXCHT. HPLC-TOF-MS/MS was used for analyzing the possible active constituents after oral administration of effective extracts in ethanol-induced gastric ulcer models. MXCHT and 4 different extracts of the bacterial inhibition diameter and MIC were dramatically decreased compared with control group, showing anti-Helicobacter pylori effects. High dose groups of MXCHT, water extract, EtOAc extract, and n-BuOH extract displayed significant anti-inflammatory effects in xylene-induced mouse ear edema model and carrageenan-induced rat paw edema model test. MXCHT and all active extracts exhibited gastroprotective activity and prevented gastric lesions induced by ethanol in rats. 4 prototype components and 4 metabolites were identified after oral administration of EtOAc extract. In addition, 6 prototype components and 6 metabolites were identified in n-BuOH extract. MXCHT, EtOAc extract, and n-BuOH extract demonstrate gastroprotective effects through anti-Helicobacter pylori and anti-inflammatory activities. Thus, this prescription may be a suitable natural source for the prevention and treatment of chronic gastritis and gastric ulcers.


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