Aspirin-induced Gastric Damage Research Articles

Effects of taxifolin on aspirin-induced gastric damage in rats: macroscopic and biochemical evaluation.

Taxifolin (dihydroquercetin) is a flavanonol isolated from various plants and has antioxidant effects. The aim of our study was to macroscopically and biochemically investigate the effects of taxifolin on aspirin-induced oxidative gastric damage in rats and to evaluate them by comparison with those of famotidine. Rats were divided into four drug administration groups: a healthy control group, an aspirin-only group (ASG), a taxifolin + aspirin group (TASG), and a famotidine + aspirin group (FASG). The results revealed that in light of the results that we obtained, 50 mg/kg taxifolin had anti-ulcer effects. At this dose, taxifolin was able to bring COX-1 activities to a level close to those seen in healthy rats with appropriate macroscopic, oxidant/antioxidant, and biochemical parameters. Based on these results, it can be said that taxifolin may be successfully used as a more potent alternative to famotidine, which is the currently accepted treatment for aspirin-induced ulcers.

Gastroprotective, hepatoprotective, and nephroprotective effects of thymol against the adverse effects of acetylsalicylic acid in rats: Biochemical and histopathological studies

Acetylsalicylic acid (Aspirin) has been used for a long time as an antipyretic and analgesic. Nevertheless, aspirin use is associated with severe morbidity and death because of its detrimental impacts on several organs, including the liver, kidneys, and stomach. The current investigation sought to ascertain the influence of thymol in mitigating aspirin-mediated gastric and hepato-renal injury. This was done by 1) evaluating gastric juice volume and pH as well as pepsin and prostaglandin E2 level; 2) measuring serum biochemical parameters and proinflammatory cytokines; 3) determining tissue oxidant/antioxidant status, and 4) identifying a link with gastric, hepatic and renal histopathological changes. Forty-eight rats were segregated to six groups: normal control, Th100, Th200, ASA, Th100 + ASA, Th200 + ASA. Daily administration of aspirin (ASA, 150 mg/kg body weight) for 3 successive days induced a significant increase in gastric juice volume, pepsin activity, serum transaminases, alkaline phosphatase, urea, creatinine, tumor necrosis factor-α, myeloperoxidase, and tissue malondialdehyde levels. In contrast, a significant reduction in gastric pH, prostaglandin E2, tissue non-enzymatic antioxidant (glutathione), and enzymatic antioxidant (superoxide dismutase, glutathione peroxidase, and catalase) levels. These biochemical changes were accompanied by histological modifications that included changes to the normal gastric, hepatic, and renal architectures. Pretreatment and simultaneous oral treatment with thymol (100 or 200 mg/kg body weight) plus ASA significantly improved all biochemical and histological changes in a dose-dependent way. Thymol's antiinflammatory and antioxidative properties may contribute to its protective action. As a result, thymol may represent a promising medication for preventing aspirin-induced gastric, liver, and renal damage.

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.

Abstract 13070: The Probiotic Bifidobacterium breve , Bif195, Supports the Defense Against Aspirin-Induced Gastrointestinal Mucosal Damage

Introduction: Low-dose aspirin (50-325 mg daily) is widely recommended for the prevention of cardiovascular disease. However, daily use of aspirin is associated with an increased risk of gastrointestinal mucosal damage including gastric and duodenal ulcers. We have recently published data on the ability of the probiotic Bifidobacterium breve , Bif195, to reduce aspirin-induced epithelial damage in the small intestine, as evaluated by capsule endoscopy. However, it remains undetermined whether Bif195 alters aspirin-induced mucosa damage in the gastric ventricle, representing a more aspirin-exposed area and hostile environment for probiotics. Methods: In a 2x4 week double-blinded, placebo-controlled, randomized, crossover clinical trial, 25 healthy men and women were asked to take a daily oral dose of 300 mg aspirin during both intervention periods, and randomized to a sequence of daily oral intake of Bifidobacterium breve , Bif195≥ 10 11 colony forming units) capsules and placebo capsules, separated by a 6 weeks washout period. Participants were subjected to a gastroduodenoscopy immediately before and in the end of each intervention period. All gastroduodenoscopies were performed by the same gastroenterologist. The primary endpoint was change in Lanza score (0-5). Furthermore, mucosal biopsies, luminal fluids and blood samples were collected. Results: Gastrointestinal damage was absent in all subjects at baseline (Lanza score 0). The score was significantly reduced with Bif195 compared to placebo, in the Gastric ventricle. Values after treatment, see the table. Conclusion: Aspirin-induced gastric mucosa damage is significantly ameliorated by intake of Bif195 resulting in a 3 times lower Lanza score compared to placebo, whereas no statistically significant difference was observed in the duodenum. Bif195 may represent a beneficial supplement to continuous aspirin treatment reducing risk of aspirin-induced upper GI mucosa damage and ulcer formation.

Gastro-protective Effects of Green Banana (Musa cavendishii Lamb.) Pulp Powder on Aspirin-induced Gastric Ulcer in Albino Rats

Green banana (Musa cavendishii) is used in the traditional medicine in Sudan to treat peptic ulcer disease. The aim of this study was to evaluate the gastro-protective effect of aqueous extract of green banana pulp powder on aspirin-induced ulcer in albino rats. The effect was studied using aspirin-induced gastric damage in rats and compared between groups which were: group 1 (negative control) received water only, group 2 (positive control) received aspirin. Groups 3 and 4 were received 0.5 g/kg and 1 g/kg of banana extract before aspirin 100 mg/kg, respectively. Groups 5 and 6 were received 0.5 g/kg and 1 g/kg of banana extract of banana extract after aspirin 100 mg/kg, respectively. The results indicate that there was a significant difference (p<0.05) in ulcer index between M. cavendishii extract treated groups 3, 4, 5, 6 with ulcer index (15.0 ± 1.31), (09.5 ± 0.64), (09.0 ± 0.79) and 0 respectively when compared to the control group with ulcer index (25.5 ± 1.45). The histopathological assessment showed significant improvement as partial erosion of mucosa with groups 3 and 4, while group 5 and 6 showed total gastric aspirin induced-ulcer protection. The study concluded that banana pulp powder suspension showed significant gastro-protective effect in all groups of rats, promotes ulcer healing and strengthens the mucosa. This study confirmed the use banana in folk medicine for the management of gastric ulcer. The mechanism of protection afforded by bananas has to be further elucidated.

Carvedilol safeguards against aspirin-induced gastric damage in rats

This study investigated the effect of carvedilol on aspirin-induced gastric damage. Male Wistar rats were divided into three groups. Control rats received the vehicle, while the aspirin group received aspirin (200 mg/kg) orally for 4 days. Rats of aspirin + carvedilol group were administered aspirin along with carvedilol (5 mg/kg; intraperitoneal) for 4 days. Animals were euthanized at the end of the treatment period, and gastric tissues were collected to perform histopathological and mechanistic studies. The results revealed that aspirin administration induced gastric ulcer as there were remarkable histopathological lesions in the form of marked necrosis, inflammation, hemorrhage, edema, and dysplastic changes. Lipid peroxidative markers such as malondialdehyde, 4-hydroxynonenal, and protein carbonyl were significantly elevated in the aspirin group. This was concurrent with a significant amelioration of antioxidants such as reduced glutathione, superoxide dismutase, and catalase. Furthermore, aspirin increased the immunoexpression of cyclooxygenase (COX) 2 and nuclear factor kappa-B (NF-κB). Aspirin induced elevation in the inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β. Aspirin enhanced the immunoexpression of inducible nitric oxide synthetase (iNOS) and increased the level of nitrite/nitrate in gastric tissue. On the other hand, carvedilol treatment reversed all these pathological changes. Carvedilol succeeded to enhance antioxidants in gastric tissue, attenuated lipid peroxidative parameters, and suppressed the release of inflammatory mediators. It attenuated the immunoexpression of COX-2, NF-κB, and iNOS. Collectively, carvedilol has a gastro-protective effect that could be attributed to its antioxidative and anti-inflammatory properties, which modulate NF-κB/COX-2/iNOS pathways.

The Possible Protective Effect of Ocimum Basilicum L. Aqueous Extract on Aspirin Induced Damage of Gastric Mucosa in Adult Male Albino Rats: Histological and Ultrastructural Study

Background and Objectives: One of the new strategies to limit the gastric mucosal injury induced by aspirin is addingantioxidant. Therefore, our aim was to detect histological changes that may occur in fundic mucosa of adult male albino ratsgiven aspirin and the protective role of Ocimum Basillicum administration.Materials and Methods: Thirty adult male albino rats were classified into three groups: Group I (control group, which weresubdivided into two equal subgroups, Group II (aspirin treated group, given aspirin in a dose of 12.5 mg/kg by orogastric tubefor 4 weeks) and Group III (coadministration group, given aspirin in the same previous dose in concomitant with Basil in adose of 200 mg/Kg b.w by orogastric tube).Results: Fundic mucosa of aspirin treated group showed disorganized fundic glands, desquamation of surface epithelial cells,mononuclear cell infiltration and congested blood vessels. Many parietal cells exhibited small nuclei with increased amount ofheterochromatin, dilated canaliculi containing few short microvilli and vacuole-like structures. Many eosinophils were seen inlamina propria. Many chief cells appeared with shrunken pyknotic nuclei and vacuolated cytoplasm. Statistically significantincrease in the mean area percent of collagen fibers and decrease in the mean thickness of mucous film in PAS stained sectionsof fundic mucosa of aspirin treated group. These changes were reduced in the coadministration group.Conclusion: Ocimum Basilicum aqueous extract has beneficial protective effects against the deleterious effects of aspirin onthe fundic mucosa. Therefore, it may be a suitable nutritional supplement or therapeutic drug to protect against aspirin-inducedgastric damage.

Olive-Derived Hydroxytyrosol Shows Anti-inflammatory Effect without Gastric Damage in Rats.

Hydroxytyrosol (HT) is a simple phenol compound present in olive oil. In a previous in vitro study, we showed that HT downregulated lipopolysaccharide-mediated expression of inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), tumor necrosis factor alpha, and interleukin-1β, resulting in reduced nitric oxide and prostaglandin E2 production. In the present study, we aimed to determine whether HT suppresses COX-2-induced inflammation in a carrageenan-induced rat paw edema model. Additionally, we compared its activity with those of the selective COX-2 inhibitor, celecoxib for a comparative control, and a representative nonsteroidal anti-inflammatory drug (NSAID), indomethacin for a positive control. HT, celecoxib, and indomethacin significantly suppressed swelling in carrageenan-injected rat paws. Although HT was less effective than celecoxib and indomethacin, it had a delayed onset of action. Moreover, we evaluated whether HT aggravates gastric damage, which is a typical adverse effect associated with NSAIDs and COX-2 inhibitors under low dose aspirin (LDA) treatment, in an aspirin-induced gastric damage rat model. Unlike celecoxib and indomethacin, HT did not cause gastric damage when co-administered with aspirin. Our results indicate that HT exerts a delayed but sustained anti-inflammatory effect against COX-2-mediated inflammation. Finally, the combination of short-acting conventional anti-inflammatory drugs and long-acting HT can be considered a new, safe, and effective anti-inflammatory treatment modality even when continuously administered for a long period under LDA treatment.

AK106-001616, a Potent and Selective Inhibitor of Cytosolic Phospholipase A2: In Vivo Efficacy for Inflammation, Neuropathic Pain, and Pulmonary Fibrosis.

3-[3-Amino-4-(indan-2-yloxy)-5-(1-methyl-1H-indazol-5-yl)-phenyl]-propionic acid (AK106-001616) is a novel, potent, and selective inhibitor of the cytosolic phospholipase A2 (cPLA2) enzyme. Unlike traditional nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors, AK106-001616 reduced prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) production by stimulated cells. The suppression of PGE2 and LTB4 production was also confirmed using an air pouch model in rats administered a single oral dose of AK106-001616. AK106-001616 alleviated paw swelling in a rat adjuvant-induced arthritis (AIA) model. The maximum effect of the inhibitory effect of AK106-001616 was comparable with that of naproxen on paw swelling in a rat AIA model. Meanwhile, the inhibitory effect of AK106-001616 was more effective than that of naproxen in the mouse collagen antibody-induced arthritis model with leukotrienes contributing to the pathogenesis. AK106-001616 dose dependently reversed the decrease in paw withdrawal threshold not only in rat carrageenan-induced hyperalgesia, but also in a rat neuropathic pain model induced by sciatic nerve chronic constriction injury (CCI). However, naproxen and celecoxib did not reverse the decrease in the paw withdrawal threshold in the CCI model. Furthermore, AK106-001616 reduced the disease score of bleomycin-induced lung fibrosis in rats. In addition, AK106-001616 did not enhance aspirin-induced gastric damage in fasted rats, increase blood pressure, or increase the thromboxane A2/ prostaglandin I2 ratio that is thought to be an underlying mechanism of thrombotic cardiovascular events increased by selective cyclooxygenase-2 inhibitors. Taken together, these data demonstrate that oral AK106-001616 may provide valuable effects for wide indications without attendant gastrointestinal and cardiovascular risks.

Nitric oxide, afferent sensory nerves, and antioxidative enzymes in the mechanism of protection mediated by tricarbonyldichlororuthenium(II) dimer and sodium hydrosulfide against aspirin-induced gastric damage

BackgroundAspirin exerts side effects within the gastrointestinal tract. Hydrogen sulfide (H2S) and carbon monoxide (CO) have been implicated in gastroprotection but the mechanism of beneficial action of these gaseous mediators against aspirin-induced damage has not been fully studied. We determined the involvement of afferent sensory neurons, calcitonin-gene-related peptide (CGRP), lipid peroxidation, and nitric oxide (NO) biosynthesis in gastroprotection of H2S-releasing NaHS and CO-releasing tricarbonyldichlororuthenium(II) dimer (CORM-2) against aspirin-induced injury.MethodsWistar rats with or without capsaicin-induced denervation of sensory neurons were pretreated with vehicle, CORM-2 (5 mg/kg intragastrically), or NaHS (5 mg/kg intragastrically) with or without capsazepine (5 mg/kg intragastrically) or NG-nitro-l-arginine (l-NNA, 20 mg/kg intraperitoneally). The areas of aspirin-induced lesions and gastric blood flow (GBF) were assessed by planimetry and laser flowmetry respectively. Gastric mucosal messenger RNA and/or protein expression of CGRP, heme oxygenase 1, inducible nitric oxide synthase, cyclooxygenase 2, interleukin-1β, glutathione peroxidase 1 (GPx-1), and superoxide dismutase was determined by real-time PCR or Western blot. Malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) content was determined by colorimetric assay.ResultsAspirin caused gastric lesions, decreased GBF, and raised MDA content, but pretreatment with NaHS and CORM-2 reduced these effects. Capsaicin-induced denervation or co-treatment with capsazepine reversed the gastroprotective and vasodilatory effects of NaHS but not those of CORM-2. l-NNA reversed NaHS-induced gastroprotection and partly reduced CORM-2-induced gastroprotection. NaHS and CORM-2 decreased MDA and 4-HNE content, restoring GPx-1 protein expression.ConclusionsWe conclude that H2S- but not CO-mediated gastroprotection against aspirin-induced injury involves afferent sensory nerves and partly NO activity. NaHS and CORM-2 prevented aspirin-induced gastric mucosal lipid peroxidation via restoration of microcirculation and antioxidative GPx-1 protein expression.

Interaction between endogenous carbon monoxide and hydrogen sulfide in the mechanism of gastroprotection against acute aspirin-induced gastric damage

Acetylsalicylic acid (ASA) is mainly recognized as painkiller or anti-inflammatory drug. However, ASA causes serious side effects towards gastrointestinal (GI) tract which limits its usefulness. Carbon monoxide (CO) and hydrogen sulfide (H2S) have been described to act as important endogenous messengers and mediators of gastroprotection but whether they can interact in gastroprotection against acute ASA-induced gastric damage remains unknown.In this study male Wistar rats were pretreated with 1) vehicle (saline, i.g.), 2) tricarbonyldichlororuthenium (II) dimer (CORM-2, 5mg/kg i.g.), 3) sodium hydrosulfide (NaHS, 5mg/kg i.g.), 4) zinc protoporphyrin (ZnPP, 10mg/kg i.p.), 5) D,L-propargylglycine (PAG, 30mg/kg i.g.), 6) ZnPP combined with NaHS, 7) PAG combined with CORM-2 or 8) 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10mg/kg i.p.) combined with CORM-2 or NaHS and 30min later ASA was administered i.g. in a single dose of 125mg/kg. After 1h, gastric blood flow (GBF) was determined by H2 gas clearance technique and gastric lesions were assessed by planimetry and histology. CO content in gastric mucosa and COHb concentration in blood were determined by gas chromatography and H2S production was assessed in gastric mucosa using methylene blue method. Protein and/or mRNA expression for cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MST), heme oxygenase (HO)-1, HO-2, hypoxia inducible factor-alpha (HIF)-1α, nuclear factor (erythroid-derived 2)-like 2 (Nrf-2), cyclooxygenase (COX)-1 and COX-2, inducible nitric oxide synthase (iNOS) and interleukin (IL)-1β were determined by Western blot or real-time PCR, respectively.ASA caused hemorrhagic gastric mucosal damage and significantly decreased GBF, H2S production, CO content, mRNA or protein expression for CSE, 3-MST, HO-2 and increased mRNA and/or protein expression for CBS, HO-1, Nrf-2, HIF-1α, iNOS, IL-1β, COX-2 in gastric mucosa and COHb concentration in blood. Pretreatment with CORM-2 or NaHS but not with PAG decreased ASA-damage and increased GBF. ZnPP reversed protective and hyperemic effect of NaHS but PAG failed to affect CORM-2-induced gastroprotection. CORM-2 elevated CO content, mRNA or protein expression for HO-1, Nrf-2, and decreased expression of CBS, HIF-1α, COX-2, IL-1β, iNOS, the H2S production in gastric mucosa and COHb concentration in blood. NaHS raised mRNA or protein expression for CSE, COX-1 and decreased mRNA expression for IL-1β and COHb level in blood.We conclude that CO is involved in gastroprotection induced by H2S while beneficial protective action of CO released from CORM-2 in gastric mucosa seems to be H2S-independent. In contrast to H2S, CO ameliorates hypoxia, regulates Nrf-2 expression but similarly to H2S acts on sGC-dependent manner to restore gastric microcirculation and exhibit anti-inflammatory activity in gastric mucosa compromised by ASA.

Tu1858 Role of Heme Oxygenase-1 and Nuclear Factor (Erythroid-Derived 2)-Like 2 Factor (NRF2) in Pathogenesis of Aspirin-Induced Gastric Damage and Protection by Carbon Monoxide

Tu1858 Role of Heme Oxygenase-1 and Nuclear Factor (Erythroid-Derived 2)-Like 2 Factor (NRF2) in Pathogenesis of Aspirin-Induced Gastric Damage and Protection by Carbon Monoxide

Microscopical Evaluation of Healing Effect of &lt;i&gt;Falcaria vulgaris&lt;/i&gt; Extract on Aspirin-Induced Gastric Ulcer in Rats

Objectives : Gastroprotective effects of herbal medicine were shown in numerous studies. Falcaria vulgaris (Ghazzayaghi) has traditionally been used for the treatment of stomach disorders in the Northwest of Iran. The present study was carried out to evaluate the microscopic healing effect of F. vulgaris extract on aspirin-induced gastric damage in rats. Materials and Methods : Thirty five young male rats were divided into five groups (7 rats/group). Control (group I) treated with 1 ml/kg distilled water. Four groups of animals had been exposed to starvation for 48 h and then received aspirin (200 mg/kg) in 1 ml carboxymethyl cellulose (CMC) 1% solvent for 3 days. Then, groups II-IV of rats were treated with 150 mg/kg extract (experimental group), 20 mg/kg omeprazole (reference group) and CMC solution (ulcer control group) by gavages for 14 days, respectively. The fifth group only received aspirin for 3 days. Three hours after last treatment rats were sacrificed and the stomachs were fixed in formalin (10%) and sections of 6 μ in diameter were prepared. Ulcer index, curative ratio, and morphological characteristics of the stomach were assessed using hematoxylin and eosin and Van Gieson staining. Data were analyzed using one-way ANOVA and post hoc Tukey test. Results : The results indicated that F. vulgaris extract significantly decreased the ulcer index (P < 0.01), increased curative ratio, and enhanced the formation of collagen fibers compare to aspirin and omeprazole groups. Conclusions : Hydroalcoholic extract of F. vulgaris showed significant microscopic healing effect on the aspirin-induced gastric ulcer.

GW26-e0712 Comparative Effects of Clopidogrel, Ticagrelor and Cilostazol on Aspirin-induced Gastric Bleeding and Damage in Stomach of Rats

To evaluate the effects of frequently used clopidogrel, ticagrelor and cilostazol on the gastric bleeding and ulcerogenic responses induced by acidified acetylsalicylic acid (ASA) in rats. 24 Sprague-Dawley rats were randomly assigned to give clopidogrel (10-100mg/kg) groups, ticagrelor (3-10 mg/kg

Comparative effects of the anti-platelet drugs, clopidogrel, ticlopidine, and cilostazol on aspirin-induced gastric bleeding and damage in rats

AimsThe present study compared the effects of frequently used anti-platelet drugs, such as clopidogrel, ticlopidine, and cilostazol, on the gastric bleeding and ulcerogenic responses induced by intraluminal perfusion with 25mM aspirin acidified with 25mM HCl (acidified ASA) in rats. Main methodsThe stomach was perfused with acidified ASA at a rate of 0.4ml/min for 60min under urethane anesthesia, and gastric bleeding was measured as the concentration of hemoglobin in the luminal perfusate, which was collected every 15min. Clopidogrel (10–100mg/kg), ticlopidine (10–300mg/kg), or cilostazol (3–30mg/kg) was given p.o. 24h or 90min before the perfusion of acidified ASA, respectively. Key findingsPerfusion of the stomach with acidified ASA alone led to slight bleeding and lesions in the stomach. The pretreatment with clopidogrel, even though it did not cause bleeding or damage by itself, dose-dependently increased the gastric bleeding and ulcerogenic responses induced by acidified ASA. Ticlopidine also aggravated the severity of damage by increasing gastric bleeding, and the effects of ticlopidine at 300mg/kg were equivalent to those of clopidogrel at 100mg/kg. In contrast, cilostazol dose-dependently decreased gastric bleeding and damage in response to acidified ASA. SignificanceThese results demonstrated that clopidogrel and ticlopidine, P2Y12 receptor inhibitors, increased gastric bleeding and ulcerogenic responses to acidified ASA, to the same extent, while cilostazol, a phosphodiesterase III inhibitor, suppressed these responses. Therefore, cilostazol may be safely used in dual anti-platelet therapy combined with ASA, without increasing the risk of gastric bleeding.

Protective role of hydrogen-rich water on aspirin-induced gastric mucosal damage in rats

To investigate the role of the hydrogen-rich water (HRW) in the prevention of aspirin-induced gastric mucosal injury in rats. Forty male rats were allocated into four groups: normal control group, HRW group, aspirin group, and HRW plus aspirin group. The protective efficacy was tested by determining the gastric mucosal damage score. Malondialdehyde (MDA), superoxide dismutase (SOD), myeloperoxidase (MPO), interleukin (IL)-06 and tumor necrosis factor (TNF)-α in gastric tissues were evaluated. The serum levels of IL-1β and TNF-α were also detected. Histopathology of gastric tissues and localization of Cyclooxygenase 2 (COX-2) were detected using hematoxylin and eosin staining and immunohistochemistry, respectively. Pretreatment with HRW obviously reduced aspirin-induced gastric damage scores (4.04 ± 0.492 vs 2.10 ± 0.437, P < 0.05). The oxidative stress levels of MDA and MPO in the gastric tissues increased significantly in the aspirin-treated group compared with the HRW group (2.43 ± 0.145 vs 1.79 ± 0.116 nmol/mg prot, P < 0.05 and 2.53 ± 0.238 vs 1.40 ± 0.208 U/g tissue, P < 0.05, respectively). HRW could obviously elevated the SOD levels in the gastric tissues (37.94 ± 8.44 vs 59.55 ± 9.02 nmol/mg prot, P < 0.05). Pretreatment with HRW significantly reduced IL-06 and TNF-α in the gastric tissues (46.65 ± 5.50 vs 32.15 ± 4.83 pg/mg, P < 0.05 and 1305.08 ± 101.23 vs 855.96 ± 93.22 pg/mg, P < 0.05), and IL-1β and TNF-α in the serum (505.38 ± 32.97 vs 343.37 ± 25.09 pg/mL, P < 0.05 and 264.53 ± 28.63 vs 114.96 ± 21.79 pg/mL, P < 0.05) compared to treatment with aspirin alone. HRW could significantly decrease the COX-2 expression in the gastric tissues (staining score: 8.4 ± 2.1 vs 2.9 ± 1.5, P < 0.05). HRW pretreatment alleviated the aspirin-induced gastric lesions by inhibiting the oxidative stress, inflammatory reaction and reducing the COX-2 in the gastric tissues.

Effect of decursinol on the aspirin-induced gastric ulcer in mice

Decursinol is one of the coumarins purified from the dried roots of Angelica gigas Nakai (Umbelliferae) and has various pharmacological effects including an analgesic property. Although aspirin is widely used to reduce pain and inflammation, aspirin-induced gastric damage remains the major limitation to its use. Therefore, the anti-ulcer activity of decursinol in aspirininduced gastric ulcer in mice was examined. One group of mice was treated orally once daily with aspirin (300 mg/kg) and another group was co-administered with decursinol (10, 25, 50, and 100 mg/kg) and aspirin (300 mg/kg) orally once daily for 5 consecutive days. On day 6, the gastric mucosae were examined. Animal groups co-administered with decursinol and aspirin exhibited a dose-dependent reduction of gastric damage against aspirin-induced gastric ulceration. The extent of inhibitions for the respective doses employed was 11.1, 15.8, 50.3, and 70.4%, respectively. These results suggest that combination therapy with aspirin and decursinol may be useful to alleviate pain and inflammation without major gastrointestinal side effects.

Comparison of Indomethacin, Diclofenac and Aspirin-Induced Gastric Damage according to Age in Rats

Background/AimsAging gastric mucosa is known to have decreased mucosal defenses and increased susceptibility to injury by nonsteroidal anti-inflammatory drugs. Depending on the type of nonsteroidal anti-inflammatory drug (NSAID), the underlying mechanisms and the extent of damage to the stomach or intestine may differ. This study was performed to evaluate the acute gastric damage caused by different doses of indomethacin, diclofenac and aspirin in rats of various ages.MethodsFor the acute models, indomethacin (10, 20 or 40 mg/kg), diclofenac (40 or 80 mg/kg) or aspirin (100 mg/kg) was given to 7- and 25-week-old and 1-year-old Sprague-Dawley rats by intragastric gavage. The gross ulcer index, damage area as assessed by imaging, histological index, myeloperoxidase (MPO) activity, and cytosolic phospholipase A2 (cPLA2) levels were measured after 24 hours.ResultsThe gross ulcer index and damage area increased with age in the presence of three NSAIDs (p<0.05). The increases in MPO levels induced by diclofenac and aspirin were significantly higher in 1-year-old than 7-week-old rats (p<0.05). cPLA2 expression induced by indomethacin (10 and 40 mg/kg) was greater in the 1-year-old rats, compared with 7-week-old rats (p<0.05).ConclusionsNSAID-induced acute gastric damage increased in a dose- and age-dependent manner.

Evaluation of Antiulcer Potential of Mimusops hexandra in Experimental Gastro Duodenal Ulcers

The study was aimed to investigate antiulcer effects of acetone extract and its different fractions Mimusops hexandra against experimental gastro-duodenal ulcers. 80% acetone extract of stem bark of Mimusops hexandra (Extract A, p.o.) and its different fractions namely diethyl ether (Extract A1, p.o.), ethyl acetate (Extract A2, p.o.) and aqueous (Extract A3, p.o.) were tested for the presence of preliminary phytoconstituents and were screened for their antiulcer potential in experimental animals using ethanol-HCl and aspirin-induced gastric damage at the dose of 500 mg kg-1p.o. Extract A2 being the most active fraction amongst all the fractions tested was also studied at different doses to find its ED50. Further, to establish the mechanism of action, Extract A2 was also tested for its effects in acetic acid-induced gastric ulcer models and cysteamine-induced duodenal ulcer. The effect was compared with cimetidine. Flavonoids (quercetin), procyanidins, saponins and triterpenoids were found to be present in bark. Oral administration of Extract A2 inhibited formation of gastric lesions induced by aspirin in a dose dependent manner. Elevated level of lipid peroxidation due to ethanol-HCl and aspirin induced gastric damage was significantly (p<0.05) reduced by the treatment with Extract A2. Further, Extract A2 at the dose of 100 mg kg-1 (p.o.) reduced extent of acetic acid induced gastric ulcer in experimental animals. Moreover, protection afforded by Extract A2 against cysteamine-induced duodenal lesions was evident from dose dependent decrease in ulcer index (p<0.05), score for intensity (p<0.05) and total lesion area (p<0.05), when compared with the control group. The antiulcer activity shown by Extract A2 in experimental gastro-duodenal ulcer could be attributed to decrease in gastric acid secretory activity along with strengthening of mucosal defensive mechanisms.

Gastroprotective effect of small centaury (Centaurium erythraea L) on aspirin-induced gastric damage in rats

The aim of this study was to determine the antiulcer and antioxidant activities of Centaurium erythraea L (small centaury) in aspirin (ASA) induced acute gastric ulcer model. The gastroprotective effect of the 50% aqueous-ethanolic small centaury (SC) extract was investigated in rats at a dose of ASA 200 mg/kg body weight. Twenty-one Sprague-Dawley albino rats were divided into three groups of seven rats each as follows: (1) control group; (2) acute ASA-treated group and (3) ASA plus SC group. At the end of the 4-h drug administration, ulcer index, oxidant and antioxidant levels were measured and compared between the groups. The percentage of lesion area to total gastric surface area (ulcer index) was significantly reduced (77%) in ASA plus SC group as compared with acute ASA-treated group. The oral administration of ASA decreased catalase (CAT), reduced glutathione (GSH), and increased lipid peroxidation (LPO) levels. Although myeloperoxidase (MPO) activity was increased by ASA, it was found to be lower in the ASA plus SC group. GSH and Vitamin A levels were determined higher in the ASA plus SC group compared with ASA group. These results suggest that SC extract protects against ASA-induced damage due to its antioxidizing activity.