Gastric Mucosal Nitric Oxide Research Articles

Piper sarmentosum Roxb. methanolic extract prevents stress-induced gastric ulcer by modulating oxidative stress and inflammation.

This study investigated the gastroprotective effect of Piper sarmentosum (PS) on stress-induced gastric ulcers in rats by measuring its effect on oxidative stress, gastric mucosal nitric oxide (NO), and inflammatory biomarkers. Twenty-eight male Wistar rats were randomly divided into four groups; two control groups (non-stress and stress) and two treated groups supplemented with either methanolic PS extract (500mg/kg body weight) or omeprazole (OMZ; 20mg/kg) orally. After 28days of treatment, the stress control, PS, and OMZ groups were subjected to water-immersion restrain stress (WIRS) for 3.5h. Gastric tissue malondialdehyde (MDA), NO, superoxide dismutase (SOD), inducible NO synthase (iNOS), SOD mRNA, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels were measured. WIRS significantly increased gastric MDA, NO, and pro-inflammatory cytokine levels compared to the non-stressed control group. PS and omeprazole supplementation significantly reduced WIRS-exposure-induced gastric ulcers and MDA, iNOS, and IL-1β levels. However, only PS reduced NO, TNF-α, and IL-6 levels, which were upregulated in this ulcer model. In conclusion, the gastroprotection afforded by PS is possibly mediated by gastric mucosal NO normalization through reduced iNOS expression and attenuation of inflammatory cytokines. PS showed a greater protective effect than omeprazole in reducing gastric lesions and NO, TNF-α, and IL-6 levels, and iNOS expression.

Gastric ulcer healing activity against acidified ethanol-induced gastric ulcer and gastroprotective mechanisms of Zingiber simaoense rhizome ethanol extract in rats

Background: Zingiber simaoense Y. Y. Qian (Zingiberaceae) rhizomes have been widely used to alleviate gastric disorders in Thai traditional medicine. Objectives: This study aimed to investigate the gastric ulcer healing activity of Z. simaoense rhizome ethanol extract (ZSE) against acidified ethanol-induced gastric ulcer and its possible gastroprotective mechanisms. Materials and Methods: The gastric ulcer healing activity of ZSE was evaluated using an acidified ethanol-induced gastric ulcer model in rats. The involvement of endogenous nitric oxide (NO) and sulfhydryl (SH) compounds in ZSE gastroprotection was also examined in addition to the determination of NO, malondialdehyde (MDA), and prostaglandin (PG) E2levels in rat gastric tissues as well as the determination of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and total phenolic content in ZSE. Results: ZSE at the dose of 240 mg/kg/day significantly accelerated gastric ulcer healing when observed on days 4 and 8 following ulcer induction. Pretreatment with either NG-nitro-L-arginine methyl ester or N-ethylmaleimide inhibited the gastroprotective activity of ZSE. Moreover, ZSE significantly increased NO and PGE2levels and decreased MDA levels in rat gastric tissues. DPPH radical scavenging activity and total phenolic compounds were also presented in ZSE. Conclusion: This study demonstrates the gastric ulcer healing activity of ZSE against acidified ethanol-induced gastric ulcer in rats. The possible gastroprotective mechanisms underlying the cytoprotective effect of ZSE might also involve gastric mucosal NO, SH compounds, and PGE2as well as its antioxidant activities.

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.

Gastric Mucosal Oxidative Stress Markers in Children with Helicobacter Pylori Infection

'Helicobacter pylori' "H. pylori" is one of the most common infections that colonizes human gastric mucosa and generates reactive oxygen and nitrogen species. The aim of this study was to evaluate the oxidative stress markers in the gastric mucosa of "H. pylori"- infected children. The present study was carried out on 60 children infected with "H. pylori" including 28 males, 32 females with their age ranging from 7-10 years and mean age value of 8.5 ± 1.65 years (Group I). This study included also 60 healthy children as a control group including 26 males and 34 females with their age ranging from 7-11 years and mean age value of 8.99 ± 1.63 years (Group II). All children were subjected to full history taking, thorough clinical examination, diagnosis of "H. pylori" infection through "H. pylori" stool antigen testing using enzyme immunoassay kit (Group I and II) and gastric antrum mucosal biopsies which were tested for urease activity using Campylobacter like organism test (CLO test) (Group I only) and measurement of gastric mucosal oxidative stress markers including Malondialdehyde (MDA), Superoxide dismutase (SOD), reduced glutathione (GSH), Catalase and nitric oxide (NO) [The sum of Nitrite (NO2 -) and Nitrate (NO3 -)]. The main clinical presentations in studied patients and controls were recurrent abdominal pain, recurrent vomiting, dyspepsia and hematemesis with no significant difference between patients and controls as regard abdominal pain, vomiting or dyspepsia but hematemesis was found only in patients. There were significant differences between patients and controls as regard site and duration of abdominal pain with epigastrium being the most common site of pain in patients versus diffuse abdominal pain in control group with significantly longer duration of abdominal pain in patients compared with controls. "H. pylori" infected children has significantly lower gastric mucosal nitric oxide and reduced glutathione and significantly higher gastric mucosal MDA, catalase and SOD compared to controls (nitric oxide was 85.68 ± 23.16 nmol/gm in patients versus 106.423±2.111 nmol/gm in controls, reduced glutathione in patients was 1.83 ± 0.16 nmol/gm versus 2.44 ± 0.07 nmol/gm in controls, MDA in patients was 189.15 ± 6.14 nmol/gm versus 166.21 ± 3.13 nmol/gm in controls, catalase was 57.38 ± 19.85 unit/gm in patients versus 36.51 ± 2.34 unit/gm in controls and SOD in patients was 375.52 ± 26.51 unit/gm versus 318.51 ± 32.06 unit/gm in controls. "H. pylori" infection is associated with gastric mucosal oxidative stress with significantly lower gastric mucosal nitric oxide and reduced glutathione and significantly higher gastric mucosal MDA, Catalase and SOD in patients compared to controls. Antioxidants may be an important adjuvant therapy for "H. pylori" infection as this infection is associated with gastric mucosal oxidative stress.

The role of apelin in the healing of water-immersion and restraint stress-induced gastric damage.

The objective of this study was to explore the role of apelin in the healing of gastric lesions induced by stress. Male Wistar rats were exposed to water immersion and restraint stress (WIRS) for 6h with or without the apelin receptor antagonist F13A. The rats were killed on the 1st, 3rd, 5th or 10th day after the end of stress induction. Apelin and hypoxia-inducible factor-1α expression was increased on the 1st day after the end of stress exposure and was decreased daily thereafter. However, F13A retarded the healing of gastric lesions by preventing the improvement of mucosal blood flow, prostaglandin E2 production and vascular endothelial growth factor expression in rats exposed to WIRS. Additionally, F13A increased the gastric 4-hydroxynonenol+malondialdehyde content on the 1st and 3rd days after the end of stress induction but did not affect the change in gastric mucosal nitric oxide levels. In conclusion, apelin may be a regulatory protein involved in the healing mechanism of stress-induced gastric damage.

Antioxidant, Anti-inflammatory, and Antiulcer Potential of Manuka Honey against Gastric Ulcer in Rats.

Gastric ulcers are among the most common diseases affecting humans. This study aimed at investigating the gastroprotective effects of manuka honey against ethanol-induced gastric ulcers in rats. The mechanism by which honey exerts its antiulcer potential was elucidated. Four groups of rats were used: control, ethanol (ulcer), omeprazole, and manuka honey. Stomachs were examined macroscopically for hemorrhagic lesions in the glandular mucosa, histopathological changes, and glycoprotein detection. The effects of oxidative stress were investigated using the following indicators: gastric mucosal nitric oxide (NO), reduced glutathione (GSH), lipid peroxide (MDA, measured as malondialdehyde) glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase. Plasma tumour necrosis factor-α, interleukin-1β, and IL-6 were also measured. Manuka honey significantly decreased the ulcer index, completely protected the mucosa from lesions, and preserved gastric mucosal glycoprotein. It significantly increased gastric mucosal levels of NO, GSH, GPx, and SOD. Manuka honey also decreased gastric mucosal MDA and plasma TNF-α, IL-1β, and IL-6 concentrations. In conclusion, manuka honey likely exerted its antiulcer, effect by keeping enzymatic (GPx and SOD) and nonenzymatic (GSH and NO) antioxidants as well as inflammatory cytokines (TNF-α, IL-1β, and IL-6) in a reduced form, inhibited lipid peroxidation (MDA), and preserved mucous glycoproteins levels.

Preventive Effects of Tocotrienol on Stress-Induced Gastric Mucosal Lesions and Its Relation to Oxidative and Inflammatory Biomarkers.

This study aimed to investigate the possible gastroprotective effect of tocotrienol against water-immersion restraint stress (WIRS) induced gastric ulcers in rats by measuring its effect on gastric mucosal nitric oxide (NO), oxidative stress, and inflammatory biomarkers. Twenty-eight male Wistar rats were randomly assigned to four groups of seven rats. The two control groups were administered vitamin-free palm oil (vehicle) and the two treatment groups were given omeprazole (20 mg/kg) or tocotrienol (60 mg/kg) orally. After 28 days, rats from one control group and both treated groups were subjected to WIRS for 3.5 hours once. Malondialdehyde (MDA), NO content, and superoxide dismutase (SOD) activity were assayed in gastric tissue homogenates. Gastric tissue SOD, iNOS, TNF-α and IL1-β expression were measured. WIRS increased the gastric MDA, NO, and pro-inflammatory cytokines levels significantly when compared to the non-stressed control group. Administration of tocotrienol and omeprazole displayed significant protection against gastric ulcers induced by exposure to WIRS by correction of both ulcer score and MDA content. Tissue content of TNF-α and SOD activity were markedly reduced by the treatment with tocotrienol but not omeprazole. Tocotrienol significantly corrected nitrite to near normal levels and attenuated iNOS gene expression, which was upregulated in this ulcer model. In conclusion, oral supplementation with tocotrienol provides a gastroprotective effect in WIRS-induced ulcers. Gastroprotection is mediated through 1) free radical scavenging activity, 2) the increase in gastric mucosal antioxidant enzyme activity, 3) normalisation of gastric mucosal NO through reduction of iNOS expression, and 4) attenuation of inflammatory cytokines. In comparison to omeprazole, it exerts similar effectiveness but has a more diverse mechanism of protection, particularly through its effect on NO, SOD activity, and TNF-α.

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.

Gastroprotective potentials of the ethanolic extract of Mukia maderaspatana against indomethacin-induced gastric ulcer in rats

This study investigated the protective effects of the ethanolic extract of Mukia maderaspatana against indomethacin-induced gastric ulcer in rats. Gastric ulceration was induced by single intraperitoneal injection of indomethacin (30 mg/kg b.wt.). M. maderaspatana extract produced significant reduction in gastric mucosal lesions, malondialdehyde and serum tumour necrosis factor-α associated with a significant increase in gastric juice mucin content and gastric mucosal catalase, nitric oxide and prostaglandin E2 levels. The volume and acidity of the gastric juice decreased in pretreated rats. The plant extract was evaluated in the gastric juice of rats, untreated has showed near normal levels in pretreated rats. The M. maderaspatana was able to decrease acidity and increase the mucosal defence in the gastric area, therefore justifying its use as an antiulcerogenic agent. Ranitidine significantly increased pH value and decreased pepsin activity and gastric juice free and total acidity. The anti-ulcer effect was further confirmed histologically.

Mechanisms of the Protective Effects of Curcumin against Indomethacin-Induced Gastric Ulcer in Rats

Background/Aims: Curcumin, a naturally occurring polyphenolic compound, exhibits anti-inflammatory and antioxidant properties that render it an attractive candidate for protection against gastric ulcer. The aim of this study is therefore to evaluate the protective effects of curcumin against indomethacin-induced gastric ulcer in rats. Methods: Gastric ulceration was induced by a single intraperitoneal injection of indomethacin (30 mg/kg). Curcumin (50 mg/kg, p.o.) was administered 30 min before ulcer induction. Results: Curcumin showed gastroprotective effects as evidenced by significant decreases in ulcer index, total acid output and pepsin activity in gastric juice in addition to gastric mucosal malondialdehyde concentration, and concomitant increases in gastric juice mucin concentration, gastric mucosal nitric oxide level and catalase and superoxide dismutase activities as compared to the indomethacin-induced ulcer group. Moreover, immunohistochemical investigations demonstrated that curcumin treatment markedly decreased expression of inducible nitric oxide synthase, nuclear factor-κB, and caspase-3. Conclusion: Curcumin protected the rats' gastric mucosa against indomethacin-induced gastric ulceration possibly, at least in part, by enhancement of the gastric mucosal barrier and reduction in acid secretory parameters in addition to antioxidant and antiapoptotic activities.

Protective effect of silymarin against ethanol-induced gastritis in rats: Role of sulfhydryls, nitric oxide and gastric sensory afferents

Silymarin has been known to exert antioxidant, anti-carcinogenic and anti-inflammatory effects. In this study, we examined the effect of silymarin on gastritis in rats. Oral administration of silymarin dose-dependently decreased gastric lesions in ethanol-induced gastritis model. Silymarin also significantly suppressed the development of gastric lesions in aspirin- or water immersion-restraint stress-induced gastritis models. Further study demonstrated that the gastroprotective effect of silymarin was blocked by nitric oxide (NO) synthase inhibitor l-NAME, SH blocker N-ethylmaleimide or TRPV1 antagonist capsazepine in ethanol-induced gastritis model. In addition, ex vivo analysis revealed that ethanol-induced decrease in gastric mucus and non-protein sulfhydryl (NPSH) groups was significantly reversed by silymarin treatment and lipid peroxidation was also suppressed by silymarin in ethanol-induced gastritis model. Taken together, these results suggest that silymarin exerts gastroprotective effects and the gastroprotective effects of silymarin might be related to the protection of gastric mucosal NO and NP-SH and the modulation of capsaicin-sensitive gastric sensory afferents.

Gastroprotective Efficacy of Coenzyme Q10 in Indomethacin-Induced Gastropathy: Other Potential Mechanisms

Though recently the mitochondrial bioenergetic coenzyme (Co)Q10 has been shown to protect against indomethacin-induced gastric ulceration, yet the full mechanistic cassettes have not been investigated. Therefore, the current investigation assessed further gastroprotective mechanisms of CoQ10 using the indomethacin-induced gastropathy model. While CoQ10 was administered at 3 dose levels to male Wistar rats, the proton pump inhibitor, pantoprazole, was given at 4 dose levels ahead of pyloric ligation and indomethacin administration. Indomethacin evoked gastric ulcerations that were associated by decreased gastric mucosal nitric oxide and glutathione levels. The NSAID reduced gastric volume and mucin content, but increased titratable acidity, acid output, and peptic activity. CoQ10, especially at the higher dose levels, as well as pantoprazole pretreatments reverted almost all diversions induced by the NSAID to different extends. Moreover, preadministration with the nonselective nitric oxide synthase inhibitor, L-NAME, boosted ulcer formation that was associated by suppression of gastric mucosal nitric oxide in CoQ10 and pantoprazole-treated groups. The current investigation shows that CoQ10 guards against gastric ulceration via its partial inhibition of titratable acidity and peptic activity, as well as enhancement of mucin secretion due to both gastric mucosal nitric oxide and glutathione replenishment, especially at the higher dose levels.

Gastroprotective effects of amygdalin on experimental gastric ulcer: Role of NO and TNF-

Natural plant origin products like amygdalin with anti-inflammatory effects are still a major part of traditional medicine. We conducted the present investigation to elucidate the amygdalin effects on alcohol-induced gastric ulcer together with the possible role of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α). Thirty-two male Wistar rats were used to study therapeutic and preventive effects of amygdalin on absolute alcohol-induced gastric ulcer. Animals were equally divided into 4 groups (n=8): (I) control, (II) Alcohol; absolute alcohol (1 ml/200 g b.w) used to induce gastric ulcer, (III) Alcohol/Amygda; amygdalin (2 mg/kg/day intramuscular) administrated for three weeks after gastric ulcer induction and (IV) Amygda/Alcohol; amygdalin was given for three weeks before gastric ulcer induction. Ulcer index, gastric acid secretion, gastric tissue’s NO metabolites andTNF-α level measured. Ulcer index was significantly decreased in Alcohol/Amygda than Alcohol group (p<0.05). Gastric tissue’s NO metabolites level and gastric acid secretion decreased in Alcohol and Amygda/Alcohol groups than control (p<0.05). Gastric tissue TNF-α level increased in Alcohol and Amygda/Alcohol rats than control group (p<0.05). The results of this study show that amygdalin protected gastric mucosa from alcohol-induced gastric ulcer. This gastroprotection may mediate via gastric mucosal nitric oxide production and TNF-α suppression. Key words: Amygdalin, gastric ulcer, nitric oxide, TNF-α.

English

Several studies have used&nbsp;Stachys&nbsp;Lavandulifolia vahl&nbsp;(S. lavandulifolia) as medicinal plant in Iranian folk medicine.&nbsp;The present investigation is designed to elucidatetherapeutic and preventive effects&nbsp;of&nbsp;S. lavandulifolia&nbsp;extract on gastric acid and pepsin secretions in experimental gastric ulcer. Thirty two Wistar male rats were used to study therapeutic and preventive effects of&nbsp;S. lavandulifolia&nbsp;extract on alcohol-induced gastric ulcer. Animals were equally (n=8) divided into 4 groups: (I) Control (II) Alcohol (1 ml/200 g/bw)&nbsp;to induce gastric ulcer&nbsp;(III) Alcohol/Lvandu (100 mg/kg bw/daily,&nbsp;S. lavandulifoliaextract was given for two weeks post alcohol administration) and (IV) Lvandu/alcohol (S. lavandulifolia&nbsp;extract was given for two weeks before alcohol administration). Ulcer index, gastric acid and pepsin secretions was measured. Ulcer index was significantly decreased in alcohol/Lvandu than Alcohol group. Also gastric acid and pepsin secretions, and gastric tissue&rsquo;s NO metabolites level were significantly lower in alcohol and Lvandu/alcohol groups than control (p&lt;0/05). But changes in gastric acid and pepsin secretions have not been noticeable in alcohol/Lvandu group than control. The results of this study show that&nbsp;S. lavandulifolia&nbsp;extract protected gastric mucosa from alcohol-induced gastric ulcer. This&nbsp;gastroprotection&nbsp;may mediate via gastric mucosal nitric oxide production. &nbsp; Key words:&nbsp;Stachys Lavandulifolia, acid, pepsin, nitric oxide.

Divergent effects of irritants on the gastric mucosa in rats during various stages after bile duct ligation

Controversy exists as to whether rats after bile duct ligation (BDL) are more susceptible to gastric mucosal damage (GMD) induced by irritants. In the present study we characterize GMD after intragastric instillation of either ethanol or hydrochloric acid (HCL), 3 and 21 days after the surgical procedure. Bile duct ligation and sham operated (SO) rats were studied. Three days after surgery, BDL rats exhibited a reduction in gastric mucosal nitric oxide synthase (NOS) activity but an increase in ethanol-induced GMD. Twenty-one days after surgery gastric mucosal prostaglandin (PG) E(2) generation in BDL rats was increased while NOS activity in both groups was similar. Ethanol-induced GMD in SO rats was higher. Pretreatment with NG-nitro-L-arginine methyl ester, prior to ethanol administration was associated with an increase in gastric mucosal PGE(2) generation: (147% in SO and 104% in BDL rats) and in GMD (176% in SO and 303% in BDL rats). HCL induced GMD was of similar magnitude in both groups in both time periods. The gastric resistance to damage by irritants in rats with BDL is not a static phenomenon. This may result from sequential changes that occur in the gastric mucosal defense mechanisms during the evolution of liver disease.

Gastroprotective Effect of Fructus Evodiae Water Extract on Ethanol-Induced Gastric Lesions in Rats

Fructus Evodiae is a widely used herbal medicine with anti-inflammatory and analgetic activities in China. The present study was designed to investigate the effect of Fructus Evodiae water extract (FE) on ethanol-induced gastric lesions in rats. Three hours before ethanol challenge, animals were intraperitoneally treated with FE (424.8 mg/kg, 141.6 mg/kg, and 47.6 mg/kg). Subsequently, we employed ex-vivo chamber technique to examine the effect of FE on gastric transmucosal potential difference (PD) changes. NO(x) (nitrate and nitrite) in gastric perfusate and gastric lesion index of whole glandular stomach were determined by intubation. The results showed that FE dose-dependently accelerated the recovery of PD reduction by ethanol, and increased NO(x) production in gastric perfusate. FE also inhibited gastric lesion formation in a dose-dependent manner. These results suggested that FE prevented ethanol-induced gastric mucosal lesions by strengthening the mucosal barrier integrity and increasing gastric mucosal nitric oxide (NO) synthesis.

The inhibition of gastric mucosal lesion, oxidative stress and neutrophil-infiltration in rats by the lichen constituent diffractaic acid

The antiulcerogenic effect of diffractaic acid (DA) isolated from Usnea longissima, a lichen species, on indomethacin (IND)-induced gastric lesions was investigated in rats. Administration of 25, 50, 100 and 200 mg/kg doses of DA and ranitidine (RAN) (50 mg/kg dose) reduced the gastric lesions by 43.5%, 52.9%, 91.4%, 96.7% and 72.7%, respectively. It is known that oxidative stress leads to tissue injury in organisms. Thus, in all treated groups of rats, the in vivo activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and the levels of reduced glutathione (GSH) and lipid peroxidation (LPO) were evaluated. IND caused oxidative stress, which resulted in LPO in tissues, by decreasing the levels of GPx, SOD and GSH as compared to healthy rats. In contrast to IND, the administration of DA and RAN showed a significant decrease in LPO level and an increase in tissue SOD, GPx and GSH levels. However, while CAT activity was significantly increased by the administration of IND, the administration of DA and RAN decreased CAT activity. The administration of IND also increased the myeloperoxidase (MPx) activity, which shows neutrophil infiltration into the gastric mucosal tissues. In contrast to IND, the administration of DA and RAN decreased MPx activity. The changes in activities of gastric mucosal nitric oxide synthases (NOS) throughout the development of gastric mucosal damage induced by IND were also studied. A decrease in constitutive NOS (cNOS) activity and an increase in inducible NOS (iNOS) activity were determined in gastric damaged tissues induced by IND. The administration of DA (100 mg/kg dose) and RAN reversed the activities of iNOS and cNOS. These results suggest that the gastroprotective effect of DA can be attributed to its enhancing effects on antioxidant defense systems as well as reducing effects of neutrophil infiltration.

Epinephrine protects against severe acute gastric bleeding in rats: role of nitric oxide and glutathione.

The aim of this study was to examine the effect of the systemic administration of epinephrine against severe acute gastric bleeding in rats. Epinephrine decreased gastric hemorrhage not only before but also after lipopolysaccharide-induced severe acute gastric bleeding. Epinephrine ameliorated severe gastric hemorrhage and decreased gastric mucosal lipid peroxidation through alpha- and beta-adrenoceptors. Epinephrine modulated alpha-adrenoceptors to increase the levels of gastric mucosal nitric oxide and glutathione. Nitric oxide synthase inhibitors potently reversed the effects of epinephrine on gastric mucosal glutathione. Thus, epinephrine might act through alpha-adrenoceptors to increase the levels of gastric mucosal nitric oxide and glutathione and thus protect against severe acute gastric bleeding in rats.