Lipid Peroxidation In Gastric Mucosa Research Articles

Saudi honey alleviates indomethacin-induced gastric ulcer via improving antioxidant and anti-inflammatory responses in male albino rats

Recent years have reported a rise in the occurrence of gastric ulceration especially among young children and adults. This study investigated the mechanism by which two types of Saudi honey: AlnahalAljawal honey (Wadi) or Bin Ghaithan honey (Talh) exerted their antiulcer potential in indomethacin-induced gastric ulceration. Four cohorts of rats were used: Group 1; Healthy controls, Group 2; Ulcerative animals, Group 3; Ulcerative + Wadi honey treatment, Group 4; Ulcerative + Talh honey treatment. We profiled the levels of different indicators of oxidative stress including the activities of gastric mucosal glutathione superoxide dismutase (SOD), catalase (CAT), peroxidase (GPx), reduced glutathione (GSH), and lipid peroxidation (measured as malondialdehyde; MDA). CRP content, IL-10, and plasma tumor necrosis factor-α were also evaluated. The stomach was visually examined for macroscopic lesions and using light microscope for histopathological changes in the glandular mucosa.Wadi or Talh honey significantly reduced the ulcer indices, and essentially protected the glandular mucosa from lesions. Wadi or Talh honey also significantly reduced the gastric mucosal concentrations of GPx, SOD and GSH. In addition, the administration of Wadi or Talh honey decreased gastric mucosal plasma TNF-α and MDA, CRP content, and IL-10 levels. In conclusion, Wadi or Talh honey possibly exerted their antiulcer potential via restoring the homeostasis and stabilizing the enzymatic (SOD and GPx) and non-enzymatic (GSH) antioxidants as well as reducing the levels of inflammatory cytokines (TNF-α, CRP content, IL-10 and, NF-κB activity), and inhibiting the lipid peroxidation in the gastric mucosa. Consequently, Wadi or Talh honey may be of beneficial therapy for patients diagnosed with gastric ulceration. Clinical studies need to be conducted to further support these findings.

Effects of curcumin on antioxidant capacity and gastric mucosal injury following strenuous endurance training in rats

Strenuous endurance training (SET) in endurance athletes can cause gastrointestinal problems, such as gastritis. Gastritis is associated with increased oxidative stress and an imbalance between free-radical production and antioxidant defences. The present study investigated the effects of SET and curcumin injection on systemic total antioxidant capacity (TAC), gastric mucosal injury and lipid peroxidation (malondialdehyde – MDA) in male rats. Twenty-six male Wistar rats were randomly divided into four groups including Control, Curcumin, Endurance, and Endurance + curcumin. Incremental endurance training (up to 70 min with 35 m/min), and curcumin injection (30 mg/kg bodyweight, three times per week) was carried out in relevant groups. The pathology of gastritis was measured concerning the restoration factors (the number of neutrophils, the formation of new vessels, and proliferation of fibroblasts), gastric MDA levels and the TAC were measured. SET-induced gastritis symptoms, such as gastric mucosal injury and lipid peroxidation and curcumin decreased systemic TAC. However, curcumin reduced exercise-induced gastric mucosal injury and lipid peroxidation. Also, serum levels of TAC were maintained at normal levels following a combination of SET and curcumin injection. These findings suggest that curcumin injection during SET could be useful for managing gastritis symptoms and improving antioxidant capacity in healthy and eutrophic rats.

Ethanol-induced gastric ulcer in rats and intervention of tert-butylhydroquinone: Involvement of Nrf2/HO-1 signalling pathway.

Gastric ulcer (GU) is the most common health concern that occurs due to alcohol consumption, smoking and physiological stress. Ethanol-induced GU in animal model resembles the pathophysiology of human ulcer. The present study was designed to investigate the cytoprotective and anti-inflammatory properties of tert-butylhydroquinone (tBHQ), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator, against gastric mucosal damage induced by acute exposure of ethanol (5 ml/kg). The intervention of tBHQ (25 and 50 mg/kg, per os (po)) and omeprazole (20 mg/kg, po) was done for 10 consecutive days. Omeprazole was chosen as a standard drug because it is prescribed for the treatment of GU. Pretreatment of tBHQ decreased gastric mucosal lesion, ulcer index, apoptotic cells and lipid peroxidation level induced by ethanol. Furthermore, the intervention of tBHQ increased gastric mucosa integrity, pH, reduced glutathione, collagen and mucus-producing goblet cells. Intervention of tBHQ increased the expression of antioxidant markers such as Nrf2, haeme oxygenase-1 and catalase and decreased the expressions of inflammatory markers such as nuclear factor kappa-light-chain-enhancer of activated B cells and cyclooxygenase-2. The cytoprotective potential of tBHQ against gastric mucosal damage might be due to its ability to enhance cellular antioxidants and anti-inflammatory responses.

Gastro-Protective and Anti-Oxidant Potential of Althaea officinalis and Solanum nigrum on Pyloric Ligation/Indomethacin-Induced Ulceration in Rats.

Recently, an alternative disease treatment approach is the research of medicaments from traditional medicine. Plants with anti-oxidant capabilities are used as herbal treatments for ulcer diseases. Medicinal/herbal extracts containing phytoconstituents have significant anti-ulcer activities in in vivo experiments on animal models, compared to reference drugs. The current study aims to inspect gastro-protective as well as in vitro and in vivo anti-oxidant potential of Althaea officinalis and Solanum nigrum extracts on pyloric-ligation/indomethacin-induced gastric-ulceration in rats. Rats were divided into six groups: normal control, gastric ulcer control, two standard pretreatment groups receiving omeprazole and misoprostol, and two test pretreatment groups receiving Althaea officinalis and Solanum nigrum. Pretreatments were administrated orally for 14 days. On the 15th day, animals, excluding the normal control group, were exposed to pyloric-ligation followed by indomethacin injection. After four hours, the rat’s stomachs were removed and gastric juice and blood samples were collected. Pyloric-ligation/indomethacin administration caused considerable elevation in ulcer number, ulcer index, acid and pepsin productivity, aggressive factors, and gastric mucosal lipid-peroxide contents. Moreover, reduction in titratable acidity, gastric mucosal nitric-oxide, anti-oxidant contents, and protective factors accompanied gastric-ulceration. Additionally, elevation in pro-inflammatory cytokines content and reduction in cystathionine-β-synthase and heme-oxygenase-1 expression was witnessed. Omeprazole, misoprostol, Althaea officinalis, and Solanum nigrum pretreatments fixed blood and tissue biomarkers, thereby protecting them from pyloric-ligation/indomethacin-induced gastric-ulceration in rats, which is hopeful for clinical examinations.

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.

Gastroprotective effect of bezafibrate, a peroxisome proliferator activated receptor α agonist and its mechanism in a rat model of aspirin-induced gastric ulcer

SummaryBackgroundThe aim of the present study was to demonstrate the antiulcer activity and mechanism of bezafibrate in a rat model of aspirin‐induced gastric ulcer.MethodsWe used an aspirin‐induced gastric ulcer model. Bezafibrate was administered orally in graded doses (10 mg/kg, 25 mg/kg, 50 mg/kg, 100 mg/kg, and 200 mg/kg) to detect the best effective antiulcer dose of bezafibrate. The parameters measured were: ulcer index, histopathological scoring of gastric ulcer, gastric juice analysis, gastric mucosal lipid peroxidation parameters, estimation of NO metabolite in blood, mRNA expression of inducible NO synthase iNOS and constitutive NO synthase (cNOS) in gastric mucosa, and gastric mucosal DNA fragmentation.ResultsThe dose‐dependent antiulcer activity of bezafibrate was shown by the ulcer index and histopathological score. Bezafibrate (100 mg/kg) significantly reduced total acidity, free acidity, and pepsin activity, and increased total hexoses and total proteins. Bezafibrate (100 mg/kg) also significantly reduced lipid peroxidation, inhibited iNOS expression, preserved cNOS expression, and inhibited DNA fragmentation.ConclusionBezafibrate can decrease aspirin‐induced gastric mucosal injury via reducing lipid peroxidation, inhibiting iNOS expression, preserving cNOS expression, and decreasing DNA fragmentation.

Prooxidant activity of norbixin in model of acute gastric ulcer induced by ethanol in rats.

Free radicals and oxidative stress play a central role in gastric injuries caused by ethanol (EtOH). Antioxidant strategies to counteract EtOH toxicity are highly desirable. Norbixin (NBIX) is a carotenoid with antioxidant potential largely used in the food industry. This study evaluated the NBIX effects in a model of gastric ulcer induced by EtOH in rats. Male Wistar rats received NBIX doses of 0, 10, and 25 mg/kg by gavage 1 h after EtOH administration (0 or 75% solution, 1 mL/200 g of animal). The animals were euthanized 1 h after the NBIX administration, and their stomachs were removed for macroscopic and histopathological analyses, quantification of nonprotein sulfhydryl (NPSH) groups, lipid peroxidation (LPO) levels, and catalase (CAT) activity determination. NBIX increased LPO in gastric mucosa and caused CAT inhibition and NPSH depletion in EtOH-treated animals. Results showed that NBIX did not protect gastric tissue against EtOH damage, and this could be associated to a prooxidant effect.

Assessment of Protective Effects of Extracts of Zingiber officinale and Althaea officinalis on Pyloric Ligation-Induced Gastric Ulcer in Experimental Animals

Gastric ulcer is one of the most gastro-intestinal disorders in world. There are many drugs used for the treatment of gastric ulcer, but most of these associates with several adverse effects. In the present study we investigate the protective effects of extracts of Zingiber officinale and Althaea officinalis on pyloric ligation-induced gastric ulcer in rats. Animals were divided into 5 groups; a normal control group, an ulcer control group, a standard treatment group receiving famotidine (20 mg/kg), and two treatment groups receiving Z. officinale extract (100 mg/kg) and A.officinalis extract (100 mg/kg). Treatments were given orally for 14 days. On the 15th day, animals were subjected to pyloric ligation except normal control group. Four hours later, rat stomachs were excised and gastric juice and blood samples were collected. Pyloric ligation significant increases ulcer number, ulcer index, gastric volume, titratble acidity, acid output, mucin content and peptic activity, accompanied by significant decreases in blood superoxide dismutase activity (SOD) activity and gastric mucosal nitric oxide (NO) and glutathione (GSH) contents. In addition, elevations in gastric mucosal lipid peroxide and histamine contents were observed. Pretreatment with famotidine, Z. officinale or A.officinalis extracts significantly corrected all blood and tissue parameters by varying degrees.Famotidine, Z. officinale and A.officinalis extractsmay protect against pyloric ligation-induced peptic ulcer in rats, being promising for further clinical trials.

Comparison between the Protective Effects of Famotidine, Ginger and Marshmallow on Pyloric Ligation-Induced Peptic Ulcer in Rats

Background: Gastric ulcer is one of the most serious diseases over wide the world. There are many drugs used for the treatment of gastric ulcer, but most of these produce several adverse reactions. This study aims to investigate the protective effects of extracts of ginger and marshmallow on pyloric ligation-induced gastric ulcer in rats. Methods: Animals were divided into 5 Groups; a normal control group, an ulcer control group, a standard treatment group receiving famotidine (20 mg/kg), and two treatment groups receiving ginger (100 mg/kg) and marshmallow (100 mg/kg). Treatments were given orally for 14 days. On the 15th day, animals were subjected to pyloric ligation except for the normal control group. Four hours later, rat stomachs were excised and gastric juice and blood samples were collected. Results: Pyloric ligation caused significant elevations in ulcer number, ulcer index, gastric volume, titratble acidity, acid output, mucin content and peptic activity, accompanied by significant decreases in blood superoxide dismutase (SOD) activity and gastric mucosal nitric oxide (NO) and glutathione (GSH) contents. In addition, elevations in gastric mucosal lipid peroxide and histamine contents were observed. Pretreatment with famotidine, ginger or marshmallow significantly corrected all blood and tissue parameters by varying degrees. Conclusions: Famotidine, ginger and marshmallow may protect against pyloric ligation-induced peptic ulcer in rats, being promising for further clinical trials.

Protective effects of ginger and marshmallow extracts on indomethacin-induced peptic ulcer in rats.

Background:Gastric ulcer is one of the most serious diseases. Most classic treatment lines produce adverse drug reactions. Therefore, this study aimed to investigate the protective effects of two natural extracts, namely ginger and marshmallow extracts, on indomethacin-induced gastric ulcer in rats.Materials and Methods:Animals were divided into five groups; a normal control group, an ulcer control group, and three treatment groups receiving famotidine (20 mg/kg), ginger (100 mg/kg), and marshmallow (100 mg/kg). Treatments were given orally on a daily basis for 14 days prior to a single intra-peritoneal administration of indomethacin (20 mg/kg).Results:Indomethacin administration resulted in significant ulcerogenic effect evidenced by significant elevations in ulcer number, ulcer index, and blood superoxide dismutase activity accompanied by significant decreases in gastric mucosal nitric oxide and glutathione levels. In addition, elevations in gastric mucosal lipid peroxides and histamine content were observed. Alternatively, pretreatment with famotidine, ginger or marshmallow significantly corrected macroscopic and biochemical findings, supported microscopically by results of histopathological study.Conclusion:These results demonstrate that administration of either ginger or marshmallow extract could protect against indomethacin-induced peptic ulcer in rats presumably via their antioxidant properties and inhibition of histamine release.

The protective effect of apelin against water-immersion and restraint stress-induced gastric damage.

The aim of the present study was to investigate the gastroprotective effect of apelin on water-immersion and restraint stress (WIRS)-induced gastric lesions. Male Wistar rats were divided into four groups: control, WIRS, F13A + WIRS and F13A. APJ receptor antagonist F13A was administered to rats to determine the influence of apelin on stress-induced gastric injury. WIRS administered for 6 h resulted in the development of gastric mucosal lesions accompanied by a significant increase in plasma corticosterone. WIRS increased the concentration of 4-hydroxynonenol (4-HNE) + malondialdehyde (MDA) and the expression of apelin and hypoxia inducible factor-1α (HIF-1α) in gastric mucosa. In addition, WIRS reduced the mucosal blood flow and gastric prostaglandin E(2) (PGE(2)) concentration. Plasma corticosterone, which was increased due to stress, was significantly decreased in the F13A + WIRS group. Gastric lesions and the 4-HNE + MDA concentration were also higher in the F13A + WIRS compared to the WIRS group. We conclude that apelin has a gastroprotective effect against stress-induced lesions possibly by reducing lipid peroxidation in gastric mucosa.

Protective Effect of 3,4-Methylenedioxyphenol (Sesamol) on Stress-Related Mucosal Disease in Rats

Stress-related mucosal disease (SRMD) causes considerable morbidity and mortality in critically ill patients. 3,4-Methylenedioxyphenol (sesamol) has been reported to have potent antioxidative and anti-inflammatory properties. The aim of this study was to investigate the effect of sesamol on water immersion restraint- (WIR-) induced SRMD in rats. Rat gastric ulcer and hemorrhage were induced by WIR. Rats were pretreated orally with various doses of sesamol (0.1, 0.3, and 1 mg/kg, resp.) 30 min before WIR. Gastric mucosal ulceration, hemoglobin, lipid peroxidation, mucus secretion, proinflammatory cytokines, and nuclear factor (NF)-κB levels were determined 4 h after WIR. In addition, the infiltration of neutrophil and macrophage into gastric mucosa was also determined after WIR. Water immersion restraint increased gastric mucosal ulcer and hemorrhage, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels but failed to affect mucosal lipid peroxidation and mucus secretion compared with non-WIR. Sesamol significantly decreased gastric ulceration and hemorrhage and inhibited mucosal TNF-α, IL-1β, and IL-6 production and NF-κB activity in WIR-treated rats. In addition, increased myeloperoxidase and CD68 levels in gastric mucosa were found in WIR-treated rats compared to non-WIR rats. Sesamol did not affect myeloperoxidase but decreased CD68 levels in mucosa in WIR-treated rats. Sesamol may protect against SRMD by inhibiting gastric mucosal proinflammatory cytokines in rats.

Evaluation of antioxidant and immunity-enhancing activities of Sargassum pallidum aqueous extract in gastric cancer rats.

The effect of Sargassum pallidum (brown seaweed) aqueous extract on the immunity function and antioxidant activities in was studied gastric cancer rats. Treatment with Sargassum pallidum aqueous extract at oral doses 400, 600 or 800 mg/kg body weight was found to provide a dose-dependent protection against N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)-induced immunity damage and oxidative injury by enhancing serum interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-10 (IL-10) levels, decreasing interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α) levels, preserving normal antioxidant enzymes activities, and by inhibiting lipid peroxidation in gastric mucosa. It can be concluded that Sargassum pallidum aqueous extract may enhance the immunity and antioxidant activities in gastric cancer rats.

Gastroprotective Effect of Selenium on Ethanol-Induced Gastric Damage in Rats

In the present study, we examined the gastroprotective effect of selenium against ethanol-induced gastric mucosal lesions in rats. The gastric mucosal lesions were produced by oral administration with various concentrations of ethanol for three days, and 80% ethanol treatment was determined to be the optimal condition for induction of gastric damage. To identify the protective effect of selenium on ethanol-induced gastric damage, various doses of selenium were given as pretreatment for three days, and then gastric damage was induced by 80% ethanol treatment. Selenium showed a protective effect against ethanol-induced gastric mucosal lesions in a dose dependent manner. Specifically, 100 μg/kg selenium showed the highest level of gastroprotection. In addition, selenium markedly attenuated ethanol-induced lipid peroxidation in gastric mucosa and increased activities of radical scavenging enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase in a dose-dependent manner. Histological data showed that 100 μg/kg selenium distinctly reduced the depth and severity of the ethanol induced gastric lesion. These results clearly demonstrate that selenium inhibits the formation of ethanol-induced gastric mucosal lesions through prevention of lipid peroxidation and activation of enzymatic radical scavenging.

Preventive Effect of Probiotics and α-Tocopherol on Ethanol-Induced Gastric Mucosal Injury in Rats

The protective effect of a probiotic mixture of 13 different bacteria and α-tocopherol on 98% ethanol-induced gastric mucosal injury was evaluated. Levels of gastric mucosal pro- and anti-inflammatory cytokines, malondialdehyde, and secretory immunglobulin A were measured. Rats were allocated into four groups: control, ethanol, probiotic, and α-tocopherol. The control and ethanol groups received skim milk for 14 days. Probiotic and α-tocopherol groups were administered probiotic mixture suspended in skim milk and 100 mg/kg α-tocopherol, respectively, by daily gavage for 14 days. On Day 15, gastric lesions were induced by administration of ethanol 98% (1 mL) to all rats except those in the control group. Probiotic, but not α-tocopherol, seemed to inhibit ethanol-induced gastric mucosal tumor necrosis factor-α, interferon-γ, and interleukin-2 production (P > .05). Ethanol caused the elevation of mucosal interleukin-4 level (compared to the control, P < .05). Probiotic pretreatment significantly suppressed the ethanol-induced increase of gastric mucosal interleukin-4 levels. Pretreatment with either probiotic or α-tocopherol inhibited the ethanol-induced increase of mucosal malondialdehyde concentration (P < .01 and P < .05, respectively). Probiotic pretreatment enhanced the gastric mucosal secretory immunoglobulin A concentration (P < .001). In conclusion, probiotic mixture and α-tocopherol reduced ethanol-induced gastric mucosal lipid peroxidation, suggesting that they may be beneficial for gastric lesions induced by lower ethanol concentration.

Octreotide ameliorates gastric lesions in chronically mild stressed rats

To evaluate the effect of chronic mild stress (CMS) on the emergence of gastric ulcers and possible modulation by octreotide, a synthetic somatostatin analogue. Adult male Wistar rats were subjected to nine different unpredictable random stress procedures for 21 d, a multifactorial interactional animal model for CMS. Octreotide was administered daily for 21 d at two dose levels (50 and 90 μg/kg) before exposure to stress procedure. Macro- and microscopical assessments were made, in addition to quantification of plasma corticosterone and gastric mucosal inflammatory, oxidative stress, and apoptotic biomarkers. Exposure to CMS elevated plasma corticosterone (28.3 ± 0.6 μg/dL, P = 0.002), an event that was accompanied by gastric lesions (6.4 ± 0.16 mm, P = 0.01) and confirmed histopathologically. Moreover, the insult elevated gastric mucosal lipid peroxides (13 ± 0.5 nmol/g tissue, P = 0.001), tumor necrosis factor-α (3008.6 ± 78.18 pg/g tissue, P < 0.001), prostaglandin E2 (117.1 ± 4.31 pg/g tissue, P = 0.002), and caspase-3 activity (2.4 ± 0.14 OD/mg protein, P = 0.002). Conversely, CMS mitigated interleukin-10 (627.9 ± 12.82 pg/g tissue, P = 0.001). Furthermore, in animals exposed to CMS, octreotide restored plasma corticosterone (61% and 71% from CMS, P = 0.002) at both dose levels. These beneficial effects were associated with a remarkable suppression of gastric lesions (38% and 9% from CMS, P = 0.01) and reversal of derangements in gastric mucosa. The current investigation provides evidence that exposure to CMS induces gastric ulceration, which was alleviated by administration of octreotide possibly possessing antioxidant, anti-inflammatory, and anti-apoptotic actions.

Octreotide Ameliorates Gastric Lesions In Chronically Mild Stressed Rats: Possible Involvement of Antioxidant, Anti‐inflammatory and Antiapoptotic Mediators.

Chronic mild stress (CMS) is linked to different pathophysiological changes that have not been thoroughly investigated. Hence, the present study aimed to evaluate the effect of random exposure to 9 different unpredictable stressors for 21 days on the emergence of hemorrhagic peptic ulcer spots in rats. The possible modulatory effect of a somatostatin‐analogue, octreotide, at two dose levels (50 and 90 μg/kg) was studied in this model of CMS. In addition, both doses of octreotide were given daily for 21 days to normal rats. Exposure to CMS produced anhedonia, increased plasma cortisol level, and reduced body weight, effects which were accompanied by typical gastric lesions confirmed histopathologyically. This insult was also able to elevate levels of gastric mucosal lipid peroxides, PGE2 and the inflammatory cytokine TNF‐α, as well as caspase‐3 activity. On the other hand, CMS mitigated the levels of the anti‐inflammatory cytokine IL‐10 and total antioxidant capacity (TAC). Octreotide administered to normal rats only suppressed gastric mucosal PGE2 level and elevated that of IL‐10. Furthermore, when administered during exposure to CMS, octreotide prevented anhedonia and maintained normal body weight partially at the low dose level and completely with the higher one. These beneficial effects were associated by a remarkable suppression of gastric lesions formation and reverted all derangements in cortisol level and the gastric mucosa, effects that were reflected microscopically. The present study shows that exposure to CMS induces gastric ulceration and that octreotide possesses antiulcer effects via antioxidant, anti‐inflammatory and anti‐apoptotic actions.

Sesame lignan sesamol protects against aspirin-induced gastric mucosal damage in rats

Non-steroidal anti-inflammatory drugs are commonly used to control pain, fever, and various inflammatory diseases; however, they have been identified as gastro-toxic. The aim of the present study was to evaluate the effect of aspirin plus sesamol on gastric mucosa in rats. Rats were given oral aspirin (30 mg/kg/d) and oral sesamol (ranging from 0 to 30 mg/kg/day) for 5 weeks, after which their gastric mucosal integrity, oxidative stress, inflammation, and neutrophil infiltration were assessed 6 h after gastric surgery. Sesamol dose-dependently decreased aspirin-induced gastric haemorrhage and mucosal ulceration, and significantly reduced (a) gastric mucosal lipid peroxidation, (b) nitric oxide production, (c) gastric mucosal proinflammatory cytokines (tumor necrosis factor-α and interleukin 1-β levels), and (d) the activity of gastric mucosal myeloperoxidase compared with aspirin-alone groups. We hypothesize that aspirin plus sesamol decreases aspirin-induced gastro-toxicity by inhibiting neutrophil infiltration and subsequent gastric mucosal inflammation and oxidative stress in rats.

Gastroprotective effect of simvastatin against indomethacin-induced gastric ulcer in rats: Role of nitric oxide and prostaglandins

This study investigated the possible mechanisms underlying the gastroprotective effect of simvastatin against indomethacin-induced gastric ulcer in rats. Rats were randomly assigned to vehicle-, simvastatin-, simvastatin + l-arginine- and simvastatin + N(G)-nitro- l-arginine methyl ester (L-NAME)-pretreated groups for two weeks. Pyloric ligation was performed for the collection of gastric juice, and gastric ulceration was induced by a single intraperitoneal injection of indomethacin (30 mg/kg). Gastric juice parameters (total acid output, pepsin activity and mucin concentration) were determined. The stomachs tissues were used for determination of gastric mucosal lipid peroxides, superoxide dismutase, catalase, total nitrites and prostaglandin E 2 levels. Pretreatment with simvastatin (10 mg/kg, orally, for 2 weeks) caused significant reduction in gastric mucosal lesions and lipid peroxides associated with a significant increase in gastric juice mucin concentration. Simvastatin significantly increased the gastric mucosal total nitrite and prostaglandin E 2 levels. Additionally, simvastatin attenuated the elevations in gastric mucosal superoxide dismutase observed with indomethacin. The gastroprotective effect afforded by simvastatin was significantly augmented by coadministration with l-arginine (a nitric oxide precursor) and inhibited by coadministration with L-NAME (a nitric oxide synthase inhibitor). Results confirm a gastroprotective effect for simvastatin, and indicate that the anti-ulcer effect of simvastatin is mediated by scavenging free radicals, increasing nitric oxide and prostaglandin E 2 levels, and increasing gastric juice mucin production. We conclude that simvastatin represents a more suitable antihyperlipidemic therapy for patients who are at risk of gastric ulcers that were induced by the use of nonsteroidal anti-inflammatory drugs (NSAIDs).

Effect of Sesame Oil on Acidified Ethanol‐Induced Gastric Mucosal Injury in Rats

Exposure of gastric mucosa to concentrated ethanol induces acute gastritis. Gastric mucosal lipid peroxidation plays a significant role in the pathogenesis of ethanol-induced gastric mucosal lesions. The aim of this study was to investigate the effect of sesame oil on acidified ethanol-induced gastric mucosal damage in rats. We performed gastric bilateral vagotomy in rats. A small incision on forestomach was made and stomach content was expelled. Normal artificial gastric acid (54 mM NaCl plus 100 mM HCl) or acidified ethanol (30% ethanol plus 150 mM HCl) was instilled into the stomach. Gastric lipid peroxidation, glutathione, and nitric oxide levels were measured 3 hours after acidified ethanol administration. Acidified ethanol caused mucosal ulceration, luminal hemorrhage, lipid peroxidation, and a lower level of mucosal glutathione and nitric oxide production. Pretreatment of sesame oil, but not mineral oil, significantly decreased acidified ethanol-induced mucosal ulcer formation and luminal hemorrhage. Sesame oil reduced mucosal lipid peroxidation, as well as glutathione and nitric oxide production in acidified ethanol-treated stomachs. Furthermore, both sesame oil and mineral oil did not affect serum ethanol concentration in acidified ethanol-treated rats. Sesame oil attenuates acidified ethanol-induced gastric mucosal injury by reducing oxidative stress in rats.