Protects Rat Gastric Mucosa Research Articles

Proanthocyanidin ameliorates against ethanol -induced gastric mucosal erosion by attenuating inflammatory response, oxidative stress and apoptosis in rats

Gastric ulcer is a common chronic disease in human digestive system. Massive alcohol drinking can lead to gastric ulcer. The gastroprotective effect and molecular mechanisms of Proanthocyanidin in a rat model of ethanol-induced gastric mucosal erosion were investigated.35 male rats were divided into five equal groups. Group 1 :( Control normal) rats received no drugs. Group 2:(Early ulcer) rats received absolute ethanol (0.5ml/100g rat) orally on empty stomach and sacrificed one hour later. Group 3 :(Early ulcer + proanthocyanidin protected) rats received proanthocyanidin orally (300mg/kg b.wt/day) for 3 weeks before ethanol administration then sacrificed after one hour. Group 4: (Late ulcer) rats received ethanol similar to group 2 and sacrificed after 21 days. Group 5: (Late ulcer + proanthocyanidin treated) rats first administered with ethanol (0.5ml/100g rat) and after one hour proanthocyanidin was administered for 21 days. A significant increase in stomach L-MDA concentration with marked decrease in CAT activity and GSH concentration were observed in gastric erosion -induced rats. However, a significant depletion of gastric L-MDA level and marked increase in CAT activity and GSH concentration were observed after Proanthocyanidin treatment when compared to ulcerated rats. A significant up-regulation of gene expression level of BAX, NF-κB and IL-1β with down-regulation of Bcl-2 gene were observed in stomach of gastric erosion -induced rats. However, a significant down regulation of BAX, NF-κB and IL-1β with up-regulation of Bcl-2 gene were observed after Proanthocyanidin treatment. Conclusively, Proanthocyanidin protects rat gastric mucosa against ethanol-induced gastric erosion via anti-inflammatory, anti- apoptotic and anti-oxidative mechanisms.

Gastroprotective effect of apricot kernel oil in ethanol-induced gastric mucosal injury in rats

ABSTRACT We investigated the gastroprotective effect of apricot kernel oil on ethanol induced gastric ulcer in rats. Male Wistar albino rats were divided into control, ethanol and apricot kernel oil + ethanol groups. The fatty acid composition of apricot kernel oil was determined using GC-MS. A gastric ulcer index was defined as the area percentage of the gastric mucosa consisting of ulcerated tissue. Gastric tissue was investigated by TUNEL staining for apoptosis, immunohistochemical iNOS staining, measurement of gastric IL-10 and IL-6 expression by ELISA and assays of catalase, malondialdehyde and superoxide dismutase. The ethanol group exhibited a higher gastric ulcer score, increased IL-6 level, increased number of inducible nitric oxide synthase-positive and TUNEL positive cells, and a higher MDA level compared to the control group. The apricot kernel oil + ethanol group exhibited significantly fewer gastric lesions compared to the ethanol group. Apricot kernel oil protects rat gastric mucosa against ethanol induced injury by its anti-inflammatory, anti-oxidative and anti-apoptotic effects, and might be useful for reducing the severity of gastric ulcers.

Astragaloside IV protects rat gastric mucosa against aspirin-induced damage

Aspirin (Asp) is commonly used as an anti-inflammatory drug, but the long-term usage of Asp can lead to severe gastrointestinal damage. Thus the co-administering of Asp with another drug that can suppress its side effect while having no impact on its anti-inflammatory activity would be ideal. Astragaloside IV (AST-IV) is a natural anti-inflammatory compound that has been shown to protect rat gastric mucosa from anhydrous ethanol-inflicted damage. In this study, we investigated whether AST-IV could protect rat gastric mucosa against Asp-induced gastric mucosal damage. Wistar rats administered 150mg/kg Asp showed significant damage to the gastric mucosa, as revealed by gastric damage score and histological evaluation. However, this was largely abolished by co-administering Asp and 25mg/kg or 50mg/kg AST-IV. The protective mechanism of AST-IV involved the suppression of Asp-induced inhibition of cycloxygenase-1 (COX-1) expression, prostaglandin E2 (PGE2) production, superoxide dismutase (SOD) activity and nitric oxide (NO) production. AST-IV blocked Asp-induced inhibition of SOD activity through preventing Asp from inhibiting the expression of SOD-1, both at the mRNA and protein levels. AST-IV did not appear to interfere with the anti-inflammatory activity of Asp since COX-2 level in model gastritis rats treated with Asp plus AST-IV was equally suppressed as in model gastritis rats treated with Asp alone. The results clearly showed that AST-IV could neutralize the toxicity of Asp while having no impact on its anti-inflammatory activity. AST-IV could therefore be considered as a potential drug for relieving the side effect associated with the long-term usage of Asp.

Taurine zinc solid dispersions protect against cold-restraint stress-induced gastric ulceration by upregulating HSP70 and exerting an anxiolytic effect

Pharmacological effects of solid dispersions (SDs) of a taurine zinc complex on gastric ulceration and anxiety were investigated. Pretreatment with taurine zinc (50, 100 or 200mg/kg) SDs dose-dependently protected rat gastric mucosa against cold-restraint stress (CRS)-induced gastric injury, and significantly attenuated increases in gastric mucosal H+K+-ATPase activity and lipid peroxidation and enhanced SOD activity. Taurine zinc also inhibited CRS-induced elevation of the serum stress hormones adrenocorticotropic hormone and corticosterone and upregulated HSP70 expression in the gastric mucosa. Moreover, taurine zinc (200mg/kg) SDs more potently protected the gastric mucosa from ulceration than the same dose of taurine, which may be attributed to a synergistic effect between taurine and zinc. Behavioral experiments in mice showed that taurine zinc SDs significantly increased the number of entries and time spent on the open arms in the elevated plus-maze test, time spent in the central area and total distance traveled in the open field test, and time spent and number of entries into the light compartment in the light/dark box test, indicative of reduced anxiety-like behaviors. This study demonstrates taurine zinc protected the gastric mucosa against CRS-induced gastric damage by decreasing oxidative stress, promoting endogenous HSP70 expression and attenuating psychological stress.

Gastroprotective effect of crocin in ethanol-induced gastric injury in rats

The present study investigated the gastroprotective effect of crocin in ethanol-induced gastric injury in rats. Rats were allocated into a normal group, an ulcer group, a crocin-treated group, an ulcer group pretreated with crocin, and an ulcer group pretreated with omeprazole as a reference anti-ulcer drug. Rats were sacrificed 3h after ethanol administration. Prophylactic administration of crocin (50mg/kg/day, i.p.) for 3 consecutive days before the administration of 70% ethanol (10ml/kg, orally) resulted in significant gastroprotection compared to ethanol-ulcerated rats as manifested by significant reduction in the gastric ulcer index. Crocin pretreatment increased ethanol-lowered levels of gastric juice mucin and mucosal prostaglandin E2 (PGE2) and interleukin-6 (IL-6). Moreover, crocin significantly decreased ethanol-elevated tumor necrosis factor-alpha (TNF-α) level, myeloperoxidase activity and heat shock protein 70 mRNA and protein levels. It also restored ethanol-altered mucosal levels of glutathione, malondialdehyde and superoxide dismutase activity. Furthermore, crocin-pretreatment alleviated ethanol-induced mucosal apoptosis as revealed by significant down-regulation of cytochrome c and caspase-3 mRNA expression, significant decrease in caspase-3 activity and mitigated DNA fragmentation as indicated by significant decrements in comet parameters. The protective efficacy of crocin was further supported by histological assessment. No significant difference was observed between crocin and omeprazole (20mg/kg orally 1h before ethanol administration) regarding their mucin-secretagogue and antioxidant effects, as well as their effects on TNF-α, IL-6 and cytochrome c. On the other hand, omeprazole was superior in enhancing PGE2 level and in alleviating neutrophil infiltration, caspase-3 activation and DNA fragmentation. Conclusively, crocin protects rat gastric mucosa against ethanol-induced injury via anti-inflammatory, anti-oxidative, anti-apoptotic and mucin-secretagogue mechanisms that are probably mediated by enhanced PGE2 release.

Gastroprotective effect of taurine zinc solid dispersions against absolute ethanol-induced gastric lesions is mediated by enhancement of antioxidant activity and endogenous PGE2 production and attenuation of NO production

Zinc plays a key role in maintaining gastric mucosal integrity, while alcohol dependency can lead to low zinc status. Complexes containing zinc have been reported to have better ability to protect gastric mucosa than the compounds alone. In this study, taurine zinc [Zn(NH3CH2CH2SO3)2] solid dispersions (SDs) were synthesized and investigated in an ethanol-induced ulcer model in rats. Gastric ulcer index; gastric mucosa malondialdehyde (MDA) level, glutathione (GSH) content, superoxide dismutase (SOD) activity and prostaglandin E2 (PGE2) production; and serum nitric oxide (NO) were assessed and histological analysis of the gastric mucosa tissue was performed. Taurine zinc (100, 200mg/kg) SDs protected rat gastric mucosa from ethanol-induced injury. Moreover, the gastroprotective effect of taurine zinc SDs was accompanied by a decrease in serum NO and significant increase in gastric prostaglandin E2 (PGE2). When indomethacin, a non-selective COX inhibitor was administered before the last dose of taurine zinc, the gastroprotective effect of taurine zinc was weakened. Furthermore, taurine zinc (200mg/kg) SDs protected against ulceration more significantly than the same dose of taurine alone, suggesting a synergistic effect between taurine and zinc. These results indicate taurine zinc protects the gastric mucosa against ethanol-induced damage by elevating antioxidants, decreasing lipid peroxidation and inhibiting the production of nitric oxide. The gastroprotective effect of taurine zinc was also partially mediated by endogenous PGE2 production.

Antimicrobial activity, acute toxicity and cytoprotective effect of Crassocephalum vitellinum (Benth.) S. Moore extract in a rat ethanol-HCl gastric ulcer model.

BackgroundA decoction of Crassocephallum vitellinum (Benth.) S. Moore (Asteraceae) is used in Kagera Region to treat peptic ulcers. This study seeks to evaluate an aqueous ethanol extract of aerial parts of the plant for safety and efficacy.MethodsAn 80% ethanolic extract of C. vitellinum at doses of 100, 200, 400 and 800 mg/kg body wt was evaluated for ability to protect Sprague Dawley rats from acidified ethanol gastric ulceration in comparison with 40 mg/kg body wt pantoprazole. The extract and its dichloromethane, ethyl acetate, and aqueous fractions were also evaluated for acute toxicity in mice, brine shrimp toxicity, and antibacterial activity against four Gram negative bacteria; Escherichia coli (ATCC 25922), Salmonella typhi (NCTC 8385), Vibrio cholera (clinical isolate), and Streptococcus faecalis (clinical isolate). The groups of phytochemicals present in the extract were also determined.ResultsThe ethanolic extract of C. vitellinum dose-dependently protected rat gastric mucosa against ethanol/HCl insult to a maximum of 88.3% at 800 mg/kg body wt, affording the same level of protection as by 40 mg/kg body wt pantoprazole. The extract also exhibited weak antibacterial activity against S. typhi and E. coli, while its ethyl acetate, dichloromethane and aqueous fractions showed weak activity against K. pneumonia, S.typhi, E. coli and V. cholera. The extract was non-toxic to mice up to 5000 mg/kg body wt, and the total extract (LC50 = 37.49 μg/ml) and the aqueous (LC50 = 87.92 μg/ml), ethyl acetate (LC50 = 119.45 μg/ml) and dichloromethane fractions (88.79 μg/ml) showed low toxicity against brine shrimps. Phytochemical screening showed that the extract contains tannins, saponins, flavonoids, and terpenoids.ConclusionThe results support the claims by traditional healers that a decoction of C.vitellinum has antiulcer activity. The mechanism of cytoprotection is yet to be determined but the phenolic compounds present in the extract may contribute to its protective actions. However, the dose conferring gastro-protection in the rat is too big to be translated to clinical application; thus bioassay guided fractionation to identify active compound/s or fractions is needed, and use of more peptic ulcer models to determine the mechanism for the protective action.

Protective effect of hydrogen sulfide against cold restraint stress-induced gastric mucosal injury in rats

Hydrogen sulfide (H2S) is an endogenous gaseous mediator plays a potential role in modulating gastric inflammatory responses. However, its putative protective role remains to be defined. The present study aimed to evaluate role of the exogenously released and endogenously synthesized H2S in cold restraint stress (CRS)-induced oxidative gastric damage in rats. Rats were restrained, and maintained at 4°C for 3h. The H2S donor, sodium hydrosulfide (NaHS) (60μmol/kg) was injected intraperitoneally (i.p.) before CRS. Our results revealed that NaHS pretreatment significantly attenuated ulcer index, free and total acid output, and pepsin activity in gastric juice along with decreased gastric mucosal carbonyl content and reactive oxygen species production. This was accompanied by increased gastric juice pH and mucin concentration in addition to restoring the deficits in the gastric reduced glutathione, catalase as well as superoxide dismutase enzyme activities. NaHS pretreatment markedly reduced the serum level of tumor necrosis factor (TNF-α) and myeloperoxidase activity compared to CRS-non-treated. Moreover, NaHS preadministration significantly abrogated the inflammatory and the deleterious responses of gastric mucosa in CRS. The protective effects of H2S were confirmed by gastric histopathological examination. However, pretreatment with the H2S-synthesizing enzyme, cystathionine-gamma-lyase inhibitor, beta-cyano-L-alanine (50mg/kg, i.p.) reversed the gastroprotection afforded by the endogenous H2S. Collectively, our results suggest that H2S can protect rat gastric mucosa against CRS-induced gastric ulceration possibly through mechanisms that involve anti-oxidant and anti-inflammatory actions alongside enhancement of gastric mucosal barrier and reduction in acid secretory parameters.

Pure tocotrienol concentrate protected rat gastric mucosa from acute stress-induced injury by a non-antioxidant mechanism

Stress has been implicated as a risk factor of various major health problems, such as stress-induced gastric mucosal injury. This study was performed to investigate the action of a pure preparation of tocotrienol (T3) concentrate, made up of 90% δ-tocotrienol and 10% γ-tocotrienol, on gastric injury of rats induced by water-immersion restraint stress (WIRS). Fourteen male Sprague-Dawley rats (200-250 g) were divided into two equal groups: a control group and a treated group. The treatment group received T3 concentrate at 60 mg/kg body weight daily for 28 days. The body weights of rats were recorded daily before the treatment was given. At the end of the treatment period, all rats were subjected to WIRS for 3.5 hours, following which the rats were euthanized. The stomachs were isolated and opened along the greater curvature for the examination of lesions and measurements of gastric malondialdehyde (MDA) and prostaglandin E₂ (PGE₂) contents. The mean gastric mucosal lesion index in the treated rats was significantly lower than that in the control rats. This suggests that the T3 concentrate has the ability to confer protection to the gastric mucosa against gastric injury induced by acute stress. No significant difference was observed for changes in body weight before and after the treatment. The gastric PGE2 content in both groups was comparable. However, the gastric MDA content was significantly higher in the treated group compared to the control group, indicating that the T3 supplementation was not able to reduce the lipid peroxidation process. This study concludes that the T3 concentrate has the ability to protect the gastric mucosa from stress-induced injury by a non-antioxidant mechanism.

Tocotrienol Attenuates Stress-Induced Gastric Lesions via Activation of Prostaglandin and Upregulation of COX-1 mRNA

The present study aims to distinguish the effect of tocotrienol on an important gastric protective factor, prostaglandin E2 (PGE2), in stress-induced gastric injury. Twenty-eight Wistar rats were divided into four groups of seven rats each. Two control groups were fed commercial rat diet, and two treatment groups were fed the same diet but with additional dose of omeprazole (20 mg/kg) or tocotrienol (60 mg/kg). After 28 days, rats from one control group and both treated groups were subjected to water-immersion restraint stress for 3.5 hours once. The rats were then sacrificed, their stomach isolated and gastric juice collected, lesions examined, and gastric PGE2 content and cyclooxygenase (COX) mRNA expression were determined. Both the regimes significantly attenuated the total lesion area in the stomach compared to the control. Gastric acidity, which was increased in stress, was significantly reduced in rats supplemented with omeprazole and tocotrienol. The PGE2 content was also significantly higher in the rats given tocotrienol supplementation compared to the control followed by an increase in COX-1 mRNA expression. We conclude that tocotrienol supplementation protected rat gastric mucosa against stress-induced lesions possibly by reducing gastric acidity and preserving gastric PGE2 by increasing COX-1 mRNA.

Vanillyl nonanoate protects rat gastric mucosa from ethanol-induced injury through a mechanism involving calcitonin gene-related peptide

Previous studies have demonstrated that capsaicin-sensitive sensory nerves are involved in the protection of gastric mucosa against damage by various stimuli and calcitoin gene-related peptide (CGRP) is a potential mediator in this process. This study was performed to explore the effect of vanillyl nonanoate, a capsaicin analog, on ethanol-induced gastric mucosal injury and the possible underlying mechanisms. A rat model of gastric mucosal injury was induced by oral administration of acidified ethanol and gastric tissues were collected for analysis of gastric ulcer index, cellular apoptosis, the activities of caspase-3, catalase and superoxide dismutase (SOD), levels of CGRP, TNF-α and malondialdehyde (MDA). The results showed that acute administration of ethanol significantly increased gastric ulcer index concomitantly with increased cellular apoptosis, caspase-3 activity, TNF-α and MDA levels as well as decreased activities of catalase and SOD. Pretreatment with 1 mg/kg vanillyl nonanoate significantly attenuated ethanol-induced gastric mucosal injury and cellular apoptosis accompanied by increase of CGRP expression, and SOD activity and decrease of caspase-3 activity, TNF-α and MDA levels. The effects of vanillyl nonanoate were inhibited by capsazepine, an antagonist of capsaicin receptor. Our results suggested that vanillyl nonanoate was able to protect the gastric mucosa against ethanol-induced gastric mucosal injury. The underlying mechanism is related to stimulation of CGRP release and subsequent suppression of ethanol-induced inflammatory reaction, cellular apoptosis and oxidative stress.

The effect of free silica on the mucosal protective and antiflatulent properties of polydimethylsiloxane.

Abstract The mucosal protective and antiflatulent properties of polydimethylsiloxane (PMS) alone, or containing free silica have been examined in rats. Both PMS and PMS + 6% silica significantly protected rat gastric mucosa from the irritant effects of aspirin but there was no significant difference between the protective effect of each agent. The antiflatulent property of PMS, as determined by X-ray measurements of foam production in the rat stomach, was significantly enhanced by the addition of free silica.

MELATONIN PROTECTS AGAINST HYDROGEN PEROXIDE‐INDUCED GASTRIC INJURY IN RATS

1. Melatonin (MT) is a pineal hormone that is also abundant in the gut and has a well known role in scavenging oxygen free radicals. The aim of the present study was to evaluate the potential protective effects of MT against H(2)O(2)-induced gastric lesions in rats. 2. An experimental model of gastric ulceration was established in rats using 15% H(2)O(2). Melatonin (12.5, 25 or 50 mg/kg, intagastrically) was administered to rats 30 min before H(2)O(2) challenge. 3. Intragastric administration of H(2)O(2) resulted in haemorrhagic lesions in the fundic area of the stomach. Furthermore, H(2)O(2) induced gastric oxidative stress, as indicated by depletion of reduced glutathione (GSH), inhibition of glutathione peroxidase (GPx) activity and elevation of malonedialdehyde (MDA) levels. These effects were accompanied by decreased gastric tissue levels of prostaglandin (PG) E(2) and nitric oxide (NO), as well as increased levels of tumour necrosis factor (TNF)-alpha. Administration of MT (12.5, 25 or 50 mg/kg) 30 min before H(2)O(2) significantly attenuated the development of gastric lesions in a dose-dependent manner. The protective effects of MT were accompanied by significant inhibition of the H(2)O(2)-induced reduction in gastric content of GSH and GPx activity and elevation in MDA levels. Furthermore, MT antagonized H(2)O(2)-induced reduction of gastric PGE(2) and NO levels and elevation of TNF-alpha. 4. In conclusion, MT protects rat gastric mucosa against H(2)O(2)-induced damage. The observed protective effects of MT can be attributed, at least in part, to its anti-oxidant properties, preservation of PGE(2) and NO levels, as well as inhibition of TNF-alpha induction in gastric tissues.

A Comparative Study upon the Cytoprotective Effect of Prostaglandin F2α and Acetaminophen on Indomethacin and Absolute Alcohol-induced Gastric Damage in Rat

This study was undertaken to investigate the comparison of the ability of a cytoprotective synthetic PGF2α and acetaminophen, to protect rat gastric mucosa against indomethacin and absolute alcohol. Fasted male rats received intragastric pretreatment of acetaminophen or either orally or IP PGF2α 30 min prior to either indomethacin (20 mg kg-1, oral suspension) or 1 mL of orally administered absolute alcohol. In another series of experiments rats were given acetaminophen concurrently with oral suspension of indomethacin or absolute alcohol. The animals were scarified 1 or 5 h after absolute alcohol or indomethacin administration respectively and the gastric mucosa was assessed for gross necrosis and for histologic changes. The results of this study showed that pretreatment with acetaminophen or PGF2α significantly reduced gross histologic changes and deep histologic necrosis versus control group. Co-administration of acetaminophen produced reduction in gastric lesions significantly, but this effect was less than when administered 30 min prior to indomethacin or absolute alcohol. The data obtained indicated effective protection of the gastric mucosa against ethanol and indomethacin injury can be achieved by oral administration of acetaminophen, probably through stimulation of gastric prostaglandins secretion. © 2007 Asian Network for Scientific Information.

Role of complement regulatory membrane proteins in ischaemia-reperfusion injury of rat gastric mucosa.

The role of complement in ischaemia-reperfusion injury has not been well investigated. 5I2 is a monoclonal antibody (mAb) directed against a rat membrane inhibitor of the C3 convertase step, which is the rat counterpart of mouse Crry/p65. 6D1 is a mAb against rat CD59 which inhibits the formation of membrane attack complexes. We visualized the tissue distribution of these membrane inhibitors in rat gastrointestinal tract by immunohistochemical staining with the appropriate mAb. Then, we tested the hypothesis that complement regulatory proteins protect rat gastric mucosa against ischaemia-reperfusion stress by using these mAbs. Gastric mucosal integrity was continuously monitored by measuring the blood-to-lumen clearance of [51Cr]-labelled ethylenediaminetetraacetic acid (EDTA) under control conditions, during ischaemia and after reperfusion. Rat 6D1 and 5I2 antigens were both widely distributed and predominantly expressed on smooth muscle and endothelial cells in gastrointestinal tracts. Blockade of complement regulatory proteins with 5I2 and 6D1 mAbs resulted in a significant increase in [51Cr]-EDTA clearance after reperfusion. These findings support the hypothesis that endogenous complement regulatory proteins may act as important protective factors against ischaemia-reperfusion stress in rat gastric mucosa.

Role of gap junctions in inhibiting ischemia-reperfusion injury of rat gastric mucosa.

Gap junctional intercellular communication (GJIC) is known to be important in the maintenance of tissue homeostasis. However, the role of GJIC in gastric mucosa has not been well investigated. We tested the hypothesis that maintenance of GJIC protects rat gastric mucosa against ischemia-reperfusion (I/R) stress by using irsogladine, an activator of GJIC, and octanol, an inhibitor of GJIC. Intragastric perfusion with octanol before ischemia resulted in a significant increase in 51Cr-EDTA clearance after reperfusion. Intraduodenal pretreatment with irsogladine attenuated the increase in 51Cr-EDTA clearance produced by octanol in a dose-dependent manner. Epithelial gap junctions reacted with anticonnexin-32 monoclonal antibodies were not changed after I/R stress alone. Intragastric perfusion with octanol caused a significant reduction in immunoreactive connexin-32 spots, which was completely reversed by irsogladine. These results indicate that inhibition of GJIC weakens the barrier function of gastric mucosa and subsequently causes damage of the barrier function in combination with I/R. Facilitation of GJIC and maintenance of gap junctions protect gastric mucosal barrier functions by potentiating cellular integrity.

Role of endogenous nitric oxide in ischaemia-reperfusion injury of rat gastric mucosa.

It has been suggested that endogenous nitric oxide may act as a protective factor for gastric mucosa since nitric oxide increases blood flow and may scavenge certain oxyradicals. We tested the hypothesis that nitric oxide protects rat gastric mucosa against ischaemia-reperfusion stress. Gastric ischaemia was induced by clamping the left gastric artery for 20 min. Rats were treated with two kinds of specific inhibitors of nitric oxide production, NG-nitro-L-arginine or NG-monomethyl-L-arginine. Gastric mucosal integrity was continuously monitored by measuring the blood-to-lumen clearance of [51chromium]-labelled ethylenediaminetetraacetic acid (EDTA) under control conditions, during ischaemia and after reperfusion. Oxidative stress in gastric mucosa was assessed by measuring dichlorofluorescein (DCF) fluorescence intensity before ischaemia and after reperfusion. Blockade of nitric oxide resulted in a significant increase in [51Cr]-EDTA clearance and DCF fluorescence intensity after reperfusion. These effects of nitric oxide inhibitors were attenuated by pretreatment with L-arginine. In conclusion, these findings support the hypothesis that endogenous nitric oxide acts as an important protective factor against ischaemia-reperfusion stress in rat gastric mucosa.

Pentagastrin gastroprotection against acid is related to H2 receptor activation but not acid secretion

Background—Pentagastrin enhances gastric mucosal defence mechanisms against acid and protects the gastric mucosa from experimental injury.Aims—To investigate whether this gastroprotection is mediated by histamine receptors or occurs as a secondary...

Increased expression of transforming growth factor α precursors in acute experimental colitis in rats

Background and aim—Epidermal growth factor (EGF) and transforming growth factor α (TGF-α), members of the EGF family of growth factors, protect rat gastric and colonic mucosa against injury. Having shown...

Ketotifen and nitroxides decrease capsaicin-augmented ethanol-induced gastric damage in rats.

Systemic administration of capsaicin aggravates ethanol-induced injury of rat gastric mucosa. We evaluated the effect of subcutaneous administration of capsaicin on the gastric mucosa and on inflammatory mediators in saline- and ethanol-treated rats. Functional ablation of primary afferent C-fibers by capsaicin (total 100 mg/kg subcutaneous) tripled ethanol-induced damage. Pretreatment with ketotifen, a mast cell stabilizer (1 mg/kg) protected rat gastric mucosa from the amplified injury induced by capsaicin and ethanol. Tempol, a selective nontoxic cell-permeable nitroxide, completely prevented the amplified gastric ulceration induced by capsaicin and ethanol. This was accompanied by a significant decrease in leukotriene B4 and C4 generation. It is therefore suggested that mast cells and free radicals contribute to the amplified injury observed in rats pretreated with capsaicin and ethanol and that the pharmacological modulation of mast cell release and scavenging of free radicals may be of therapeutic efficacy in the prevention of gastric injury.