Aspirin-induced Gastric Injury Research Articles

Vitamin D3 mitigates aspirin-induced gastric injury by modulating gastrokines, E-cadherin, and inhibiting NLRP3 and NF-κB/MMP-9 signaling pathway.

The prevalence of gastric ulcers has grown significantly in the modern era affecting 10 % of global population. Aspirin downregulates gastrokines 1(GKN1) expression in gastric mucosa and GKN1 down-regulation results in gastric cancer. Vitamin D3 (Vit.D3) has anti-inflammatory and antioxidant effects. Study the gastroprotective impact of Vit.D3 following aspirin-induced gastric injury in relation to gastrokines and investigate the possible underlying mechanisms. 24 rats were divided into 4 groups: control, Vit.D3 supplemented normal, aspirin-induced gastric injury, and Vit.D3 supplemented gastric injury groups. Some oxidative stress markers with gene expression of GKN1&2, mucin 5AC (Muc5ac) and NLR family pyrin domain containing 3 (NLRP3) in the gastric tissue were done. Histopathological and immunohistochemical study of E-Cadherin, nuclear factor kappa beta (NFκB), and metalloproteinase-9 (MMP-9) in the stomach mucosa were identified. Vit.D3 supplementation significantly upregulated E-Cadherin, GSH, GKN1and Muc5ac in the gastric tissue. Also, it improved the morphology, histology of gastric tissue, by alleviating oxidative stress and NFκB, MMP-9 and down regulation of inflammasome (NLRP3). Vitamin D3 has a potential protective effect against aspirin -induced gastric injury via upregulating gastrokine1 and E-cadherin and down regulation of NFKB/MMP-9 signaling pathway and NLRP3 inflammasome.

Gastroprotective Effect of Anisomeles indica on Aspirin-Induced Gastric Ulcer in Mice.

Gastric ulcers are commonly seen in the upper gastrointestinal tract and may be related to the Helicobacter pylori infection and the use of aspirin, a nonsteroidal anti-inflammatory drug (NSAID). Typically, proton-pump inhibitors (PPIs) are used to treat gastric ulcers; however, adverse effects have emerged following long-term treatment. Natural medicines are used as alternative therapeutic agents in the treatment of gastric ulcers, with few side effects. Despite various reports on the anti-H. pylori and anti-gastric cancer activities of Anisomeles indica, its gastroprotective effect on ulcers remains undetermined. This study investigated the protective effect of A. indica on aspirin-induced gastric ulcers in murine models. Our results show that three fractions of ethanol-extracted A. indica inhibited aspirin-induced gastric injury. Among these, A. indica Fraction 1 was observed to enrich ovatodiolide, which effectively diminished gastric acidity and alleviated aspirin-induced inflammation in the stomach. Our results provide evidence that A. indica could be developed as an effective therapeutic agent for gastroprotective purposes.

Role of Acacia Catechu in Regulating Connective Tissue Components during Experimental Gastric Ulcer Healing

Aim: To determine the healing properties of different doses of Acacia catechu on histopathological changes induced by aspirin in the stomach of adult albino rats. Methods: In an experimental study which was carried out at Postgraduate Medical Institute for a period of 21 days, forty-eight adult albino rats were included. The animals were divided into four groups by ballottement. Every group was further subdivided into three groups based on the day of sacrifice. BDH (British drug houses) provided Aspirin in powder form, and the bark of Acacia catechu was obtained from Government College University (Botany Department). The study was approved by institutional Ethical Review Committee. Results: Increased number of fibroblasts were seen in the groups taking acacia catechu, signifying healing, compared to aspirin only group. After applying one-way ANOVA, a statistically significant difference was observed among the groups on day 7 and day 14 (P-value <0.01*). However, on day 3, an insignificant difference was seen among the groups (P-value = 0.97). Conclusion: Acacia catechu has a protective role against aspirin-induced gastric injury, by inhibiting inflammation. Keywords: Fibroblast, Acacia catechu, ulcer, wound healing.

Alleviating Aspirin-Induced Gastric Injury by Binding Aspirin to β-Lactoglobulin.

PurposeGastric injury is a major issue for long-term administration of aspirin. In this work, we tried to explore the possibility of using BLG to alleviate aspirin-induced gastric injury, because of excellent abilities of BLG in loading drug molecules.MethodsVarious spectroscopic techniques and molecular docking methods were applied to investigate the interaction mechanism between BLG and aspirin. Animal experiments were performed to figure out the effects of taking aspirin-BLG on the stomach.ResultsOur results demonstrate that aspirin could bind with BLG to form stable aspirin-BLG complex (the binding constant Kb= 2.051 × 103 M−1). The formation process is endothermic (∆H>0) and the main acting force is hydrophobic force. Our data also show that the aspirin-BLG complex is formed with a higher affinity in simulated gastric fluid and could remain stable for several hours, which might arise from its special binding mode under acidic condition and the resistance of BLG to gastric digestion. Furthermore, animal models (rats with aspirin-induced gastric damage) were built. The results of animal experiments reveal that the oral administration of aspirin-BLG could cause less damage to gastric tissue, and it also hardly triggers obvious inflammatory responses.ConclusionThis study would contribute to an in-depth understanding of the interaction mechanism between BLG and aspirin. It is reasonable to believe that using BLG to bind with aspirin would be a potential way to alleviate the aspirin-induced gastric injury.

Role of the Outer Inflammatory Protein A/Cystine–Glutamate Transporter Pathway in Gastric Mucosal Injury Induced by Helicobacter pylori

INTRODUCTION:Helicobacter pylori infection is a major cause of gastrointestinal diseases. However, the pathogenesis of gastric mucosal injury by H. pylori remains unclear. Exogenous glutamate supplementation protects against gastric mucosal injury caused by H. pylori. Previously, we showed that aspirin-induced gastric injury is associated with reduction in glutamate release by inhibition of cystine–glutamate transporter (xCT) activity. We hypothesized that the xCT pathway is involved in H. pylori-induced gastric mucosal injury. In this study, we tested the activity of xCT and evaluated the regulatory effect of outer inflammatory protein (Oip) A on xCT in H. pylori-induced gastric mucosal injury.METHODS:In the H. pylori-infected mice and cell lines, the activity of xCT and the regulatory effect of microRNA on xCT were tested, and the effect of OipA from H. pylori on xCT activity was observed.RESULTS:The results of in vivo and in vitro experiments showed that H. pylori infection induced gastric mucosal injury. This was accompanied by a reduction in xCT activity, which was attenuated by exogenous glutamate treatment. Furthermore, the expression of miR-30b was upregulated, and miR-30b inhibitors significantly restored xCT activity and gastric mucosal injury caused by H. pylori infection. The OipA, a virulence protein from H. pylori, significantly upregulated the expression levels of miR-30b and inhibited xCT activity.DISCUSSION:OipA plays a significant role in H. pylori-induced gastric mucosal injury, and the effects are mediated by micro30b/xCT pathway.

PCV39 ECONOMIC IMPACT OF SWITCHING FROM ENTERIC COATED ASPIRIN TABLETS TO LIQUID FILLED CAPSULES WITH A NOVEL PHARMACEUTICAL LIPID-ASPIRIN COMPLEX IN PATIENTS SURVIVING AN ACUTE CARDIOVASCULAR EVENT

A new, pharmaceutical lipid-aspirin complex (PL-ASA) formulation has been specifically developed to reduce the risk of aspirin-induced gastric injury. In clinical studies PL-ASA liquid-filled capsules were shown to have significantly higher rates of complete aspirin response compared with the current standard of care (enteric coated aspirin tablets [EC-ASA]). Aspirin response has been linked to avoidance of ischemic events such as myocardial infarction MI) or stroke. In the current analysis we sought to determine the economic impact of switching patients from EC-ASA to PL-ASA for the first year following an index MI or stroke.

Role of Outer Inflammatory Protein A/Cystine-Glutamate Transporter Pathway in Gastric Mucosa Injury Induced by <i>Helicobacter pylori</i>

Background: Helicobacter pylori (Hp) infection is a major cause of gastrointestinal disease. However, the pathogenesis of gastric mucosa injury by Hp remains unclear. Our previous research has been shown that aspirin-induced gastric injury was associated with reduction of glutamate release by inhibiting cystine-glutamate transporter (xCT) activity. It's likely that the xCT pathway may be involved in Hp-induced gastric mucosa injury. Methods: In the Hp-infected animals, cell lines and patients, the activity of xCT and the regulatory effect of miRNA on xCT were tested, and the effect of OipA from Hp on xCT activity was observed. Findings: In vivo and vitro experiments, Hp infection induced gastric mucosa injury with a reduction of xCT, which was attenuated by exogenous glutamate treatment. The expression of miR-30b and miR-27a was up-regulated, and miR-30b/27a inhibitors significantly attenuated gastric mucosa injury and reduction of xCT activity by Hp infection. Furthermore, the outer inflammatory protein A (OipA), a virulence protein from Hp, significantly up-regulated the expression of miR-30b and decreased the activity of xCT. These results suggested that micro30b/xCT mediated OipA plays a significant role in gastric mucosa injury induced by Hp. Interpretation: OipA is one of classical virulence protein from Hp, which promotes inflammatory cytokines secretion and heightens gastric inflammation. In our study, the effect of OipA on the microRNA/glutamate pathway in Hp-induced mucosa injury was observed. Glutamate has exhibited protective effect on gastric ulcer. Thus, OipA, besides promotive effect of gastric mucosa injury (promoting inflammation), may attenuate protective effect of gastric tissue itself on damage (inhibiting glutamate activity). Funding Statement: This work was supported by the National Natural Science Foundation of China (No. 81573486 to Yuan-Jian Li, No. 81703592 to Jie Du, No. 81770739 to Zhi-Cheng Gong). It is also supported by the Open Sharing Fund for the Large-scale Instruments and Equipments of Central South University. Declaration of Interests: The authors declare they have no conflict of interests. Ethics Approval Statement: All protocols of animal experiments were approved by the Central South University Veterinary Medicine Animal Care and Use Committee and all procedures were performed according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Clinical research project was approved by the Third Xiangya Hospital, Hunan, China (approval number: 2015-S109).

Spirulina ameliorates aspirin-induced gastric ulcer in albino mice by alleviating oxidative stress and inflammation

Aspirin is a commonly prescribed non steroidal anti-inflammatory drug, but its prolonged use injures the gastric mucosa. The present study was carried out to evaluate the ameliorative effect of spirulina against aspirin-induced gastric ulcer in albino mice. Gastric ulcer was induced by oral administration of aspirin (500 mg/kg bw). Spirulina (250 and 500 mg/kg bw) was given orally for 3 days after the induction of gastric ulcer. Spirulina ameliorated aspirin-induced gastric ulcer by improving the gross morphology, histology and mucous layer of gastric tissue, augmenting the endogenous enzymatic and non-enzymatic antioxidants (reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase) and the cytoprotective marker (COX-1), and by alleviating tissue levels of the lipid peroxidation marker (malondialdehyde) and inflammatory mediators (TNF-α, COX-2 and NO). In conclusion, spirulina has a therapeutic potential in aspirin-induced gastric injury by alleviating oxidative stress and inflammation.

Increased expression of tight junction protein occludin is associated with the protective effect of mosapride against aspirin-induced gastric injury.

Mosapride is known to affect gastric motility, however whether mosapride has anti-ulcergenic effects in gastric mucosal injury is unclear. The aim of the present study was to investigate the effects of mosapride on aspirin-induced gastric injuries. GES-1 cells were cultured and divided into 5 groups: Control group, aspirin injury group (treated with 18.2 mmol/l aspirin) and mosapride pretreatment groups (treated with 0.4, 0.5, or 0.6 µmol/l mosapride). Cell proliferation was evaluated via MTT assay and cell apoptosis was investigated via flow cytometry. The expression of occludin was determined by western blot analysis. A total of 40 male Sprague-Dawley rats were randomized into five groups: Control group, aspirin injury group (150 mg/kg) and mosapride pretreatment groups (0.25, 0.50 or 0.75 mg/kg). Gastric mucosal lesions were induced by administering 200 mg/kg aspirin daily for 4 days. Rats in the mosapride groups were pretreated with mosapride 1 h prior to aspirin administration. Histological changes were evaluated under a light microscope and gastric epithelial TJs were observed via transmission electron microscopy. The results revealed that cell apoptosis was significantly increased in the aspirin injury group compared with the control (P<0.05), whereas apoptosis was significantly decreased in the mosapride pretreatment groups compared with the aspirin group (P<0.05). Cell viability was significantly increased in the mosapride pretreatment groups compared with the aspirin injury group (P<0.05), and that of the aspirin injury group was significantly decreased compared with the control group (P<0.05). Compared with the aspirin injury group, occludin expression was significantly increased in the three mosapride pre-treatment groups (all P<0.05). It was also demonstrated that gastric damage was significantly attenuated in the mosapride pretreatment groups compared with the aspirin injury group (P<0.05). Impaired TJ integrity was observed in aspirin injury group, whereas TJs in the mosapride groups were almost intact. In conclusion, the results of the present study suggest that mosapride exerts a gastroprotective action on aspirin-induced gastric mucosal injury at least in part via attenuating cell apoptosis and increasing occludin expression.

Artesunate affords protection against aspirin-induced gastric injury by targeting oxidative stress and proinflammatory signaling.

Prolonged use of aspirin, a commonly prescribed non steroidal anti-inflammatory drug, is well known to produce gastrointestinal toxicity which could be minimized by various anti-secretory agents. The present study was carried out to evaluate the protective effect of artesunate against aspirin induced gastric injury in rats. Gastric injury was induced in fasted Wistar rats by oral administration of aspirin. The effect of 50 and 150mg/kg of artesunate was studied on macroscopic changes, gastric secretions, histology, oxidative stress and inflammatory markers in the stomach tissue after 5h of induction of gastric injury. Immunohistochemical analysis for the expression of IL-1β, IL-6, NF-κB(p65) and COX-2 was also carried out. The effect of artesunate was compared with that of standard anti-ulcer drug famotidine (20mg/kg). Artesunate pretreatment produced a dose-dependent reduction in aspirin induced gastric injury and restored the gastric juice parameters. It normalized the tissue levels of oxidative stress markers (glutathione, malondialdehyde and superoxide dismutase activity) and mediators of inflammation (myeloperoxidase and TNF-α). The protection afforded by artesunate was evident from the histoarchitecture of stomach tissue and marked reduction in tissue expression of IL-1β, IL-6, NF-κB(p65) and COX-2. The effect of artesunate was found to be comparable to that of standard drug famotidine. Artesunate markedly ameliorated aspirin induced gastric injury in rats by targeting oxidative stress and COX-2 dependent as well as COX-2 independent proinflammatory signaling pathways and could have a therapeutic potential in gastric ulcer disease.

Metabolomic analysis of the effects of omeprazole and famotidine on aspirin-induced gastric injury

Gastric mucosal ulceration and gastric hemorrhage are frequently associated with treatment by non-steroid anti-inflammatory drugs (NSAIDs); however, no convenient biomarker-based diagnostic methods for these adverse reactions are currently available, requiring the use of endoscopic evaluation. We recently reported five biomarker candidates in serum which predict gastric injury induced by NSAIDs in rats, but were unable to clarify the mechanism of change in the levels of these biomarker candidates. In this study, we performed capillary electrophoresis–mass spectrometry-based metabolomic profiling in stomach and serum from rats in which gastric ulcer was induced by aspirin and prevented by co-administration of omeprazole and famotidine. Results showed drug-induced decreases in the levels of citrate, cis-aconitate, succinate, 3-hydroxy butanoic acid, and O-acetyl carnitine in all animals administered aspirin. In contrast, aspirin-induced decreases in the level of 4-hydroxyproline were suppressed by co-administration of omeprazole and famotidine. We consider that these changes were due to the prevention of gastric ulcer and decrease in the amount of collagen in stomach tissue by omeprazole and famotidine, without prevention of the NSAID-induced depression of mitochondrial function. In addition, the decreases in 4-hydroxyproline in the stomach was also detectable as changes in the serum. While further study is needed to clarify limitations of indications and extrapolation to humans, this new serum biomarker candidate of gastric injury may be useful in the monitoring of NSAID-induced tissue damage.

H(2)S-Releasing Aspirin Protects against Aspirin-Induced Gastric Injury via Reducing Oxidative Stress

The aim of this study was to examine the effect of ACS14, a hydrogen sulfide (H2S)-releasing derivative of aspirin (Asp), on Asp-induced gastric injury. Gastric hemorrhagic lesions were induced by intragastric administration of Asp (200 mg/kg, suspended in 0.5% carboxymethyl cellulose solutions) in a volume of 1 ml/100 g body weight. ACS14 (1, 5 or 10 mg/kg) was given 30 min before the Asp administration. The total area of gastric erosions, H2S concentration and oxidative stress in gastric tissues were measured three hours after administration of Asp. Treatment with Asp (200 mg/kg), but not ACS14 (430 mg/kg, at equimolar doses to 200 mg/kg Asp), for 3 h significantly increased gastric mucosal injury. The damage caused by Asp was reversed by ACS14 at 1–10 mg/kg in a concentration-dependent manner. ACS14 abrogated Asp-induced upregulation of COX-2 expression, but had no effect on the reduced PGE2 level. ACS14 reversed the decreased H2S concentrations and blood flow in the gastric tissue in Asp-treated rats. Moreover, ACS14 attenuated Asp-suppressed superoxide dismutase-1 (SOD-1) expression and GSH activity, suggesting that ACS14 may stimulate antioxidants in the gastric tissue. ACS14 also obviously inhibited Asp-induced upregulation of protein expression of oxidases including XOD, p47phox and p67phox. In conclusion, ACS14 protects Asp induced gastric mucosal injury by inhibiting oxidative stress in the gastric tissue.

Gastric injury caused by low-dose aspirin therapy in consecutive Japanese patients: a prospective study

Low-dose aspirin (<325 mg/day), administered to those with several conditions involving ischemic disorders, can cause upper gastrointestinal (GI) complications. In this prospective study, we aimed to clarify the incidence of aspirin-induced gastric ulcers in consecutive Japanese patients and identify suitable preventive measures. We recruited 125 consecutive adult outpatients who received low-dose aspirin (enteric-coated tablets 100 mg) for >8 weeks. Endoscopy and blood tests were used to evaluate their gastric injury (which was scored using a modified Lanza scale) and anti-Helicobacter pylori antibody titer, respectively. We found that 39.8% of patients received either no upper GI drug or only mucoprotective drugs, 39.8% received medium-dose histamine H2 blockers, and 20.4% received proton-pump inhibitors (PPIs). Anti-H. pylori antibody titers were positive in 43.7% of patients. The incidence of definitive gastric ulcers in this population was 0.97%. Ordered logistic regression analysis revealed that the odds ratio for the increase in the modified Lanza score was 0.20 for medium-dose histamine H2 blockers and 0.09 for PPIs. The incidence of postoperative definitive gastric ulcers in Japanese patients receiving ≤100 mg enteric-coated aspirin was 0.97%. The use of PPIs and histamine H(2) blockers may prevent aspirin-induced gastric injury in such patients.

Helicobacter pylori and Non‐malignant Diseases

It is well known that Helicobacter pylori infection is associated with many nonmalignant disorders such as gastritis, peptic ulcer, gastroesophageal reflux disease (GERD), gastric polyp, nonsteroidal anti-inflammatory drug (NSAID)/aspirin-induced gastric injury, and functional dyspepsia. In 2008, interesting articles on the association of H. pylori infection with these disorders were presented, some of which intended to reveal the mechanisms of inter-individual differences in response to H. pylori infection, and have demonstrated that genetic differences in host and bacterial factors as well as environmental factors account for these differences. A decline in the occurrence of peptic ulcer related to H. pylori was confirmed. An inverse relationship between H. pylori infection and GERD was also confirmed but the impact of gastric atrophy on the prevention of GERD remained debatable. For NSAID-induced gastric injury, eradication of H. pylori infection has been recommended. During this year, eradication of H. pylori infection was recommended for patients treated with antiplatelet therapy as well as aspirin and NSAID. It was also reported that for patients with functional dyspepsia, eradication of H. pylori offers a modest but significant benefit.

T1069 Effect of Low-Dose Administration of Lansoprazole On the Gastric Mucosal Lesions Induced By Low-Dose Aspirin in Relation to Intragastric pH in Healthy Volunteers with Different CYP2C19 Genotypes

Backgrounds and Aims: Given the major role gastric acid plays in the development of aspirininduced gastric mucosal lesions, proton pump inhibitors (PPIs) are now employed as firstline therapy in treating aspirin-related gastrointestinal disorders. Low-dose PPIs are also expected to have a similar preventive effect on aspirin-induced gastric injury. PPIs are metabolized by CYP2C19 in the liver, and their therapeutic effects are influenced by CYP2C19 genotype status. However, the effect of low-dose PPI on aspirin-induced gastric mucosal injury in relation to gastric acidity in humans has not been examined. Here, we investigated the relationship between intragastric pH and aspirin-induced gastric mucosal lesions with regard to CYP2C19 genotype status in healthy subjects receiving aspirin with and without a low-dose administration of lansoprazole. Methods: Fifteen Helicobacter pylori-negative subjects with different CYP2C19 genotype statuses (5 RMs, 5 intermediate metabolizers [IMs], and 5 poor metabolizers [PMs]) were each administered a series of three 7-day regimens of 15 mg of lansoprazole alone, 100 mg of aspirin alone, and both 15 mg of lansoprazole and 100 mg aspirin, with the order randomized among individuals. A washout period of 2 weeks or more was provided between regimens. Gastric mucosal injury was endoscopically evaluated on day 7 of each dosing period based on the modified Lanza score (MLS). 24-hour intragastric pH monitoring was started after endoscopy. Results: Median values (range) of MLS were 0 (0-1) in controls, 0 (0-1) in subjects receiving 15 mg of lansoprazole alone, 3 (0-5) in subjects receiving aspirin alone, and 0 (0-1) in subjects receiving both aspirin and 15 mg of lansoprazole. Lansoprazole increased the intragastric pH and significantly prevented aspirin-induced gastric mucosal injury (p = 0.0009 for aspirin and lansoprazole 15 mg). MLSs were negatively correlated with 24-hour intragastric pH (r = -0.740, P < 0.0001), whereas aspirin had no effect on intragastric pH. With regard to treatment with aspirin and lansoprazole 15 mg, although median values of MLS did not differ among the three genotype groups, median values of intragastric pH during treatment with this regimen were higher in PMs than in RMs and IMs (P = 0.009 for RMs, P = 0.028 for IMs). Conclusion: We observed a significant relationship between 24-hour intragastric pH and grade of aspirin-induced gastric mucosal lesions. Further, the acid inhibition attained on administration of 15 mg of lansoprazole appeared sufficient to prevent aspirin-induced gastric mucosal damage, irrespective of CYP2C19 genotype status.

Preliminary Trial of Rebamipide for Prevention of Low-Dose Aspirin-Induced Gastric Injury in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Study

Although low-dose aspirin is widely used, since it is a cheap and effective means of prevention of cardiovascular events, it can cause hemorrhagic gastrointestinal complications. The aim of this study was to evaluate the efficacy of rebamipide in preventing low-dose aspirin-induced gastric injury. A randomized, double-blind, placebo-controlled, crossover trial was performed in twenty healthy volunteers. Aspirin 81 mg was administered with placebo or rebamipide 300 mg three times daily for 7 consecutive days. The rebamipide group exhibited significant prevention of erythema in the antrum compared with the placebo group (p = 0.0393, respectively). Results for the body and fornix did not differ significantly between the placebo and rebamipide groups. In conclusion, short-term administration of low-dose aspirin induced slight gastric mucosal injury in the antrum, but not in the body or fornix. Rebamipide may be useful for preventing low-dose aspirin-induced gastric mucosal injury, especially which confined to the antrum.

Apple polyphenol extracts prevent aspirin-induced damage to the rat gastric mucosa

Aspirin causes gastroduodenal ulcers and complications. Food bioactive compounds could exert beneficial effects in the gastrointestinal tract. We evaluated whether apple polyphenol extract (APE) reduced aspirin-induced injury to the rat gastric mucosa. Rats were treated with APE (10(-4) m catechin equivalent) before oral aspirin (200 mg/kg). Cyclo-oxygenase-2 (COX-2), transforming growth factor-alpha (TGF alpha) and heparin-binding epidermal-growth-factor-like growth factor (HB-EGF) mRNA and protein expression were assessed by RT-PCR and Western blot analysis, respectively; malondialdehyde (MDA) was determined by HPLC; gastric secretion was evaluated in pylorus-ligated rats. APE decreased acute and chronic aspirin injury both macroscopically and microscopically (approximately 50 % decrease in lesion score; P < 0.05). Aspirin up-regulated mRNA and protein expression of COX-2 and HB-EGF, but not of TGF alpha; APE reduced aspirin-induced mRNA and protein over-expression of COX-2 and HB-EGF; aspirin significantly increased gastric MDA and this effect was counteracted by APE pre-treatment. APE did not significantly affect gastric acid secretion. In conclusion, APE reduces aspirin-induced gastric injury independently of acid inhibition. We speculate that APE might be of therapeutic use in the prophylaxis of aspirin-related gastropathy.

A novel water-soluble vitamin E derivative protects against aspirin-induced gastric mucosal injury in rats

Oxygen radical-mediated lipid peroxidation and neutrophil activation may be involved in the development of gastric mucosal injury induced by non-steroidal anti-inflammatory drugs (NSAIDs). Vitamin E is one of the lipid-soluble antioxidants and is generally considered to protect against lipid peroxidation of the cell membrane and to scavenge singlet oxygen and superoxide anion radicals. Our object was to investigate the antioxidative effects of water-soluble vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetra-methylchroman-6-ol (TMG), on aspirin-induced gastric mucosal injury in rats. Gastric injury was induced by intragastric administration of aspirin and 0.15 N HCl in male Sprague-Dawley rats. TMG dissolved in physiological saline was injected intraperitoneally 0.5 h before the aspirin administration. The intragastric administration of acidified aspirin induced hyperemia and hemorragic erosions in rat stomach. The increase in total area of gastric erosions was reduced by pretreatment with TMG in a dose-dependent manner. The increases of thiobarbituric acid-reactive substances (TBA-RS) and myeloperoxidase (MPO) activity 3 h after aspirin administration were significantly inhibited by pretreatment with TMG. The gastric concentration of cytokine-induced neutrophil chemoattractants-1 (CINC-1) increased after aspirin administration, and the increase was also inhibited by pretreatment with TMG. These results suggest that TMG is effective for the treatment of aspirin-induced gastric injury. This anti-inflammatory effect of TMG seems to be related to impairment of lipid peroxidation, neutrophil function and cytokine production in gastric mucosa.

The Role of Transforming Growth Factor α Formulation on Aspirin-Induced Ulcer Healing and Oxidant Stress in the Gastric Mucosa

Transforming growth factor (TGF) alpha accelerates wound healing, especially in gastric ulcers. Transforming growth factor alpha can be affected by acid and pepsin in the gastric juice. Oxidative stress also plays a role in the formation of gastric lesions. This study was designed (1) to investigate the effects of microemulsion dosage form on the healing of gastric ulcers, and (2) to determine the relationship between oxidative mechanisms and TGF-alpha during ulcer healing. Gastric ulcers were induced in Wistar rats (male, 200 +/- 25 g), by 150 mg/kg acidified aspirin application. The animals were divided into five groups consisting of 7-11 animals. The rats were killed after ulcer induction with aspirin (acute ulcer), or 2 days after ulcer induction (chronic ulcer), or after the daily application of microemulsion and TGF-alpha for 2 days. The ulcer area was measured planimetrically. Thiobarbituric acid reactive substance, glutathione, and gastric mucus levels of tissues were measured by spectrophotometric methods. The total nitric oxide level was measured by a VCl3/Griess assay. Statistical comparisons were made by an analysis of variance and the Mann-Whitney U-test. The ulcer area and malondialdehyde level of gastric tissue both decreased and the glutathione level increased to intact gastric tissue levels, while the mucus and total nitric oxide levels increased significantly after the application of intragastric TGF-alpha. These findings suggest that TGF-alpha accelerates the healing process after aspirin-induced gastric injury, and a relationship was observed between this application and the oxidative reactions.

The Effect of Dosing Interval on the Efficacy of Misoprostol in the Prevention of Aspirin-Induced Gastric Injury

The Effect of Dosing Interval on the Efficacy of Misoprostol in the Prevention of Aspirin-Induced Gastric Injury