Ethanol-induced Gastric Damage In Rats Research Articles

Gastroprotective effect of sumatriptan against indomethacin-, stress- and ethanol-induced gastric damage in male rats: Possible modulatory role of 5-hydroxytryptamine 1B/1D receptors and pro-inflammatory cytokines.

The current study was aimed to investigate the beneficial effect of sumatriptan, a 5-hydroxytryptamine 1B/1D (5HT1B/1D ) receptor agonist, on gastric ulcer in rats via stimulating 5HT1B/1D receptors and suppressing pro-inflammatory cytokines. Rats were allocated into three models of gastric ulcer: indomethacin (30 mg/kg, PO), water immersion restraint stress (WRS) and ethanol (5ml/kg PO). Animals were administered with sumatriptan (0.01, 0.1, 0.3 and 1mg/kg, i.p) 30 min before gastric ulcer induction. GR-127935 (0.01 mg/kg, i.p, a selective 5HT1B/1D antagonist) was administered 30 min before sumatriptan (0.1mg/kg) injection. Macroscopic assessments (J-score), ELISA analysis of tumour necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) and histopathological changes were performed on the rat's stomach tissues. Gastric ulcer induction in three models caused an increase in J-score, TNF-α, IL-1β and microscopic features. Sumatriptan (0.1mg/kg) significantly improved gastric injury induced by indomethacin, WRS and ethanol through the reduction in the J-score, TNF-α, IL-1β and microscopic lesions. Concurrent administration of GR-127935 (0.01 mg/kg) with sumatriptan (0.1mg/kg) reversed the gastroprotective effect of sumatriptan in three models. Sumatriptan possessed gastroprotective effects on indomethacin-, WRS- and ethanol-induced gastric damage in rats via the possible involvement of the 5HT1B/1D receptors.

<p>Gastroprotective Effect of DLBS2411 Bioactive Fraction from <em>Cinnamomum burmannii</em> Against Ethanol-Induced Gastric Damage in Rats</p>

BackgroundThe study was carried out to evaluate the anti-ulcerative and gastroprotective effect of DLBS2411, a bioactive fraction from Cinnamomum burmannii (Nees & T. Nees) Blume, in Wistar rats (Rattus norvegicus).MethodsThe rats were divided into five treatment groups, which were the Normal control group, Negative control group (ethanol-induced) and two treatment groups: DLBS2411 at the doses of 25 mg/kg body weight (BW) and 50 mg/kg BW, and the Positive control group treated with sucralfate at the dose of 100 mg/kg BW. Gastroprotective effect was measured by the ulcerative lesion index, ulcer surface area, percentage of lesion area, and cure ratio. Hematological and histopathological analyses were also conducted to gain additional data regarding the gastroprotective effect of DLBS2411 in the rats’ stomachs.ResultsDLBS2411 was found to contain not less than 15% of total phenolic compounds. Treatment with DLBS2411 at doses of 25 mg/kg BW and 50 mg/kg BW significantly reduced the percentage of ulcer area in rats. The percentage of ulcer area for the Negative control group and both doses in the DLBS2411 treatment group reached 22.64±6.82%, 6.75±4.41%, and 6.18±4.63%, respectively. Ulcer surface area in the treatment groups and Positive control group also decreased. Histopathological data showed that gastric epithelial cells in the Negative control group were more severely ulcerated than in the treatment group of DLBS2411 and the Positive control group.ConclusionThis study showed that DLBS2411 at the dose of 50 mg/kg BW was more effective in protecting the stomach lining than DLBS2411 at the dose of 25 mg/kg BW, as measured by percentage of ulceration inhibition and the ulcerative lesion index.

Protective effects of β-glucan isolated from highland barley on ethanol-induced gastric damage in rats and its benefits to mice gut conditions.

Gastrointestinal tract disease is a global health problem which affects a major part of the world population. In this study, the gastroprotective effects of β-glucan isolated from highland barley on ethanol-induced gastric damage in rats and its benefits to mice gut health were investigated. Biochemical and pathological analysis methods were adopted to evaluating the gastrointestinal tract protective of β-glucan isolated from highland barley. In the ulceration model, it was found that β-glucan treatment could mitigate the gastric lesions and gastric mucosal damage caused by ethanol, decrease the gastric ulcer index. Furthermore, β-glucan treatment alleviated the gastric oxidative stress injury in vehicle rats through increasing the activity of superoxide dismutase and catalase, decreasing the level of malondialdehyde. In addition, β-glucan treatment also could decrease the level of interleukin-6 and tumor necrosis factor alpha and increased level of prostaglandin E2, nitric oxide. In the mouse gut health promoting model, β-glucan treatment increased the colon length, faces water contents and the concentration of total short-chain fatty acids (SCFAs) both in mice colon and cecum. Taken together, these results may indicate that β-glucan isolated from highland barley exert protective effects on the gastrointestinal tract of laboratory rodents.

Bioactivity evaluations of betulin identified from the bark of Betula platyphylla var. japonica for cancer therapy.

Identification of bioactive natural products with anticancer activity as well as alleviating effects on chemotherapy-induced side effects has significant implications for cancer treatment. Betula platyphylla var. japonica, commonly known as Asian white birch, has been used in Chinese traditional medicine for a variety of purposes. In this study, the medicinal properties of betulin from B. platyphylla var. japonica useful for cancer management were investigated. LC/MS analysis revealed that betulin is a main chemical component of the EtOH extract of B. platyphylla var. japonica bark, and betulin was isolated from EtOH extract using an LC/MS-guided isolation method. Its structure was identified with 1H and 13C NMR spectroscopic data and LC/MS analysis and then compared to the previously reported spectroscopic and physical data. We first verified the cytotoxicity of betulin against three human lung adenocarcinoma cell lines, A549, H1264, and Calu-6, with IC50 values ranging from 18.7 to 39.6μM. Regarding alleviation of side effects associated with anticancer chemotherapy, betulin ameliorated cisplatin-induced renal cell damage to 80% of the control value from the concentration of 5μM. In addition, betulin showed anti-gastritis activity against ethanol-induced gastric damage in rats and notably reduced the gastric damage index compared to control in a concentration-dependent manner. These findings provide the first experimental evidence for potential use of B. platyphylla var. japonica as a functional food for cancer treatment that simultaneously alleviates the side effects of chemotherapy.

Antigastritis effects of Armillariella tabescens (Scop.) Sing. and the identification of its anti-inflammatory metabolites.

This study demonstrates the biological and chemical analysis of the mushroom Armillariella tabescens (Scop.) Sing. (Tricholomataceae). Chemical structures of the isolates were determined by 1D and 2D NMR, and ESI-MS, as well as comparison with previously reported data. All isolates were tested for anti-inflammatory effects based on their ability to inhibit LPS-stimulated nitric oxide (NO) production in RAW264.7 cells. We found that the MeOH extract of the fruiting bodies of A. tabescens showed antigastritis activity against ethanol-induced gastric damage in rats and notably reduced the gastric damage index compared to control in a concentration-dependent manner. Chemical investigation of the MeOH extract led to the isolation of four steroids (1-4), three alkaloids (5-7), two nucleic acids (8-9) and four fatty acids (10-13). This is the first study to report the identification of all isolates, except for compound 7, from A. tabescens. Compounds 1, 2, 3, 4 and 10 showed inhibition on LPS-stimulated NO production. Treatment with compound 10 inhibited expression of iNOS, COX-2, phospho-IKKα, IKKα, phospho-IκBα, IκBα and NF-kappa B in LPS-stimulated RAW264.7 cells. Compound 10 likely contributes to the health benefits of A. tabescens as an antigastritis agent through its anti-inflammatory effects.

Protective effects of polysaccharide from Dendrobium nobile against ethanol-induced gastric damage in rats

Dendrobium nobile is a medicinal herb in traditional China and Southeast Asian countries. Employing a rat model of ethanol-induced gastric ulcer, we examined the protective effect of polysaccharide (JCP) extracted from Dendrobium nobile and explored the related mechanisms. Oral administration with 100mg/kg and 300mg/kg body weight JCP for days can significant prevent the formation of gastric ulcer. Moreover, JCP pretreatment could alleviate ethanol-induced histological damage, antioxidant activities, the level of epidermal growth factor, gastric concentration of prostaglandin E, and regulate the signaling pathways of mitogen-activated protein kinases and matrix metalloproteinases. This study investigated the ethanol-induced gastric ulcer protective effect of JCP for the first time, and elucidated that the protective mechanisms.

Protective Effect of Extract from Rumex Aquaticus Herba on Ethanol-induced Gastric Damage in Rats

Background/Aims: In this study, we investigated the gastroprotective effect of extract including quercetin-3-O-β-<smlcap>d</smlcap>-glucuronopyranoside (EIQ) from Rumex aquaticus herba against the ethanol-induced gastric damage in rats. Methods: The rats were divided into eight groups composed of a non-ethanol group, only EIQ (10 mg/kg) group, groups with absolute ethanol after pretreatment with various doses of EIQ (1, 3 and 10 mg/kg), rebamipide (10 mg/kg), stillen (40 mg/kg) and a control receiving only absolute ethanol. Ethanol-induced gastric lesions, lipid peroxidation, neutrophil infiltration and glutathione level were measured. Superoxide dismutase (SOD) and catalase activity were assessed by an assay kit. Protein expression of SOD, catalase or hemoxygenase-1 (HO-1) was assessed by western blotting analysis. Results and Conclusion: In the absolute ethanol treated group, gastric lesion and malondialdehyde levels were significantly increased with enhanced myeloperoxidase activity. Administration of EIQ 1 h prior to ethanol treatment significantly inhibited the formation of gastric lesions and the elevation of the malondialdehyde levels with myeloperoxidase activity. In addition, pretreatment with EIQ significantly increased the level of glutathione, and elevated the activity and protein expression of radical scavenging enzymes, such as SOD, catalase and HO-1. EIQ may exert anti-inflammatory and anti-oxidative effects against ethanol-induced gastric injury through the reduction of lipid peroxidation, myeloperoxidase activity and free radicals.

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.

Effects of osutidine (T-593) and its enantiomers on gastric mucosal hemodynamics and mucosal integrity in anesthetized rats.

T-593 (osutidine, CAS 140695-21-2) is a new anti-ulcer agent that consists of two enantiomers, (+)-(R)-T-593 and (-)-(S)-T-593. The present study was designed to investigate the effects of T-593, (+)-(R)-T-593 and (-)-(S)-T-593 on ethanol-induced gastric damage in rats. Rats were given intraperitoneal administration of vehicle, racemic T-593, (+)-(R)-T-593 or (-)-(S)-T-593. 30 min later, the rats intragastrically received a 1-ml solution of 40% ethanol, and 30 min thereafter, they were sacrificed for assessment of gastric damage. Gastric hemodynamics were assessed by reflectance spectrophotometry and laser Doppler flowmetry during the experiment. Gastric damage was significantly suppressed by racemic T-593 in a dose-dependent manner. While 60 mg/kg of (+)-(R)-T-593 and (-)-(S)-T-593 also suppressed ethanol-induced gastric injury, the same dose of racemic T-593 exerted the most potent anti-ulcerative activity. Both (+)-(R)-T-593 and racemic T-593 increased gastric mucosal blood flow and abolished gastric mucosal blood flow stasis induced by 40% ethanol. Although (-)-(S)-T-593, which antagonizes histamine H2-receptors, exerts an antiulcerative effect, (+)-(R)-T-593 also protects the gastric mucosa from ethanol-induced injury, possibly by influencing gastric mucosal hemodynamics. Thus racemic T-593 may protect the gastric mucosa by antagonizing H2-receptors and by enhancing gastric circulation in rats.

Role of Capsaicin-Sensitive Primary Afferent Neurons and Non-protein Sulphydryl Groups on Gastroprotective Effect of Amifostine Against Ethanol-Induced Gastric Damage in Rats

Amifostine has been widely tested as a cytoprotective agent against a number of aggressors in different organs. Recently, a gastroprotective effect was observed for this drug in a model of indomethacin-induced gastric injury. Our objective was to investigate the effect of amifostine on ethanol-induced gastric injury and the role played in this mechanism by afferent sensory neurons, non-protein sulfhydryl groups, nitric oxide, ATP-sensitive potassium channels, and cyclooxygenase-2. Rats were treated with amifostine (22.5, 45, 90, or 180 mg/kg, PO or SC). After 30 min, the rats received absolute ethanol (5 ml kg(-1), PO). One hour later, gastric damage was quantified with a planimeter. Samples from the stomach were also taken for histopathological assessment and for assays of non-protein sulfhydryl groups. The other groups were pretreated with L-NAME (10 mg kg(-1), IP), glibenclamide (10 mg kg(-1), PO), or celecoxib (10 mg kg(-1), PO). After 30 min, the animals were given amifostine (90 mg kg(-1), PO or SC), followed 30 min later by gavage with absolute ethanol (5 ml kg(-1)). Other rats were desensitized with capsaicin (125 mg kg(-1), SC) 8 days prior to amifostine treatment. Amifostine administration PO and SC significantly and dose-dependently reduced ethanol-induced macroscopic and microscopic gastric damage by restoring glutathione levels in the stomach mucosa. Amifostine-promoted gastroprotection against ethanol-induced stomach injury was reversed by pretreatment with neurotoxic doses of capsaicin, but not by L-NAME, glibenclamide, or celecoxib. Amifostine protects against ethanol-induced gastric injury by increasing glutathione levels and stimulating the afferent sensory neurons in the stomach.

Sildenafil reduces the alcohol‐induced gastric damage: just say ‘NO’

British Journal of Pharmacology (2008) 153, 1764; doi:10.1038/bjp.2008.103

Role of the NO/cGMP/KATP pathway in the protective effects of sildenafil against ethanol‐induced gastric damage in rats

Sildenafil is a selective inhibitor of cGMP-specific phosphodiesterase. Sildenafil, acting via NO-dependent mechanisms, prevents indomethacin-induced gastropathy. Activation of ATP-sensitive potassium channels (K(ATP)) is involved in gastric defence. Our objective was to evaluate the role of the NO/cGMP/K(ATP) pathway in the protective effects of sildenafil against ethanol-induced gastric damage. Rats were treated with L-NAME (1 or 3 mg kg(-1), i.p.) or with L-arginine (200 mg kg(-1), i.p.) + L-NAME (3 mg kg(-1), i.p.), the guanylate cyclase inhibitor, ODQ (10 mg kg(-1), i.p.), glibenclamide (0.1, 0.3, 1 or 3 mg kg(-1), i.p.) or with glibenclamide (1 mg kg(-1), i.p.) + diazoxide (3 mg kg(-1), i.p.). After thirty minutes, the rats received sildenafil (1 mg kg(-1), by gavage), followed by intragastric instillation of absolute ethanol (4 ml kg(-1)) to induce gastric damage. One hour later, gastric damage (haemorrhagic or ulcerative lesions) was measured with a planimetry programme. Samples of stomach were also taken for histopathological assessment and for assays of tissue glutathione and haemoglobin. Sildenafil significantly reduced ethanol-induced gastric damage in rats. L-NAME alone, without L-arginine, significantly reversed the protection afforded by sildenafil. Inhibition of guanylate cyclase by ODQ completely abolished the gastric protective effect of sildenafil against ethanol-induced gastric damage. Glibenclamide alone reversed sildenafil's gastric protective effect. However, glibenclamide plus diazoxide did not alter the effects of sildenafil. Sildenafil had a protective effect against ethanol-induced gastric damage through the activation of the NO/cGMP/K(ATP) pathway.

The Role of Zinc Sulfate and Metallothionein in Protection Against Ethanol-Induced Gastric Damage in Rats

In this study, the effects of zinc sulfate against ethanol-induced acute gastric damage in rats were investigated, morphologically and biochemically. In addition, the present investigation has demonstrated the distribution of metallothionein stimulated by zinc in gastric mucosal tissues, immunohistochemically. The gastric damage was induced by intragastric administration of 1 ml absolute ethanol per rat. Rats received zinc sulfate (100 mg/kg/day) for 3 consecutive days 2 hr prior to the administration of absolute ethanol. Acute ethanol exposure caused degenerative morphological changes, a decrease in metallothionein immunreactivity; an increase in lipid peroxidation (LPO) levels, and a decrease in reduced glutathione (GSH) levels in gastric mucosa. On the other hand, zinc sulfate administration to ethanol-treated rats caused a significant reduction in the histological damage, an increase in metallothionein immunreactivity, a decrease in LPO levels, and an increase in GSH levels in gastric mucosa. As a result, the present study indicates that zinc sulfate has a protective effect against ethanol-induced acute gastric damage. In addition, we might say that the zinc given as exogenous protection against acute gastric damage has a protective effect both by stimulation of metallothionein synthesis and through GSH as well as having antioxidative potential.

Role of nitric oxide in the gastro-protective effect of lithium

Background and aim: Lithium is widely used for the management of neuropsychiatric symptoms in bipolar disorders. A few studies have shown that lithium has a protective effect against gastric damage with an unknown mechanism. Some of the actions of lithium are mediated through nitric oxide (NO), which has an important role in the regulation of gastric wall blood flow as well as gastric mucosal integrity. The aim of this study was to test the hypothesis if the gastro-protective effect of lithium is mediated through NO. Methods: Male Wistar rats were pre-treated with either a non-selective NO synthase inhibitor ( N G-nitro- l-arginine, 10 mg/kg), a selective inducible NO synthase inhibitor (aminoguanidine, 100 mg/kg) or saline. Lithium carbonate (10, 20, 50 and 100 mg/kg) was then administered intraperitoneally 1 h before the induction of gastric mucosal damage. Gastric damage was induced by either water immersion stress or ethanol gavage in rats. Results: Lithium had a significant protective effect in both stress and ethanol-induced gastric damage, but it needed in ethanol-induced gastric damage a higher dose than in the stress induced lesion. Lithium carbonate doses 20 and 50 mg/kg produced plasma concentrations that were in the range of human therapeutic Li levels (0.6–1.0 μM). Pre-treatment of animals with N G-nitro- l-arginine (20 and 40 mg/kg) reduced the protective effect of lithium against ethanol-induced gastric damage, but not in stress-induced damage. Aminoguanidine administration showed no effect on the damage reduction either in control or lithium treated rats. Conclusions: The results indicate that NO might play a role in the gastro-protective effect of lithium against ethanol-induced gastric damage in rats.

Drugs acting at the GABAA receptor attenuate ethanol-induced gastric mucosal damage in vitro.

1. Benzodiazepines (BZ) have been reported to protect against ethanol-induced gastric damage in rats in both in vivo and in vitro models. However, the effects of some drugs in the new in vitro model do not agree with results reported previously in in vivo studies. 2. Therefore, the aim of the present study was to modify the new in vitro model to a model that more closely resembles the in vivo model and, using the new in vitro model, to reassess the gastroprotective effects of some BZ and to assess the effects of some new compounds. 3. The rat stomach was isolated from the whole animal and kept in aerated Krebs' solution at 37 degrees C in an organ bath. Gastric mucosal damage was induced by instillation of 1 mL of 100% ethanol into the stomach. Drugs or their vehicle were administered inside the bath 15 min before ethanol instillation into the stomach. One hour after the instillation of ethanol, the stomach was removed from the organ bath, opened along the greater curvature and then examined for gastric mucosal damage. 4. The results indicate that, compared with vehicle pretreatment, ethanol-induced gastric mucosal damage was significantly reduced in a dose-dependent manner by pretreatment with clonazepam, a drug that acts as an agonist at central BZ sites of the GABAA receptor, and Ro 15-4513, a partial inverse agonist at BZ sites of the GABAA receptor. Flumazenil (an antagonist of central BZ sites of the GABAA receptor) did not affect gastric mucosal lesions provoked by ethanol. However, flumazenil significantly reversed the mucosal protective effects of clonazepam and Ro 15-4513. 5. CGS 9896 (a partial agonist at BZ sites of the GABAA receptor, with anxiolytic and anticonvulsant but no sedative effects) did not offer any protection against ethanol-induced gastric mucosal damage. Ro 5-3663, an atypical BZ that binds to the picrotoxin site of the GABAA receptor and reported to be a potent convulsant and only a weak antagonist of GABA, did not show any protection against the development of lesions. 6. The results suggest local gastric mediation of the effects of ethanol, as well as the gastric protective effects of BZ, through an action at local central-type BZ sites of the GABAA receptor located in the rat stomach.

Pharmacological screening of the anti-ulcerogenic effects of some Jordanian medicinal plants in rats

Ethanolic extracts of 18 medicinal plants traditionally used in Jordan for the treatment of gastric ulcers were evaluated for their possible anti-ulcer activity. Among the tested plants, 12 extracts lowered the severity of ethanol-induced gastric damage in rats with curative ratios ranging from 62.9 to 99.5%. The most active extract was that of Quercus coccifera, with a curative ratio of 99.5%.

Effects of aqueous extracts from Quercus ilex L. root bark, Punica granatum L. fruit peel and Artemisia herba-alba Asso leaves on ethanol-induced gastric damage in rats.

The gastroprotective effect of tannic acid and the aqueous extract of Quercus ilex L. root bark, Punica granatum L. fruit peel and Artemisia herba-alba Asso leaves was investigated in the rat against ethanol-induced damage. Tannic acid, Q. ilex and P. granatum extracts gave 100% precipitation of ovine haemoglobin in vitro, whereas A. herba-alba extract was devoid of any protein-binding property. Oral administration of these plant extracts or tannic acid induced a significant decrease in gastric lesions (47.7%-76%). The observed protection was more pronounced when the test solution was given at the same time with ethanol, except for Q. ilex extract. The acid content of the stomach was significantly increased by P. granatum (368%) and A. herba-alba (251%) extracts prepared in ethanol. It is suggested that monomeric and polymeric polyphenols can strengthen the gastric mucosal barrier.

Role of dorsal motor nucleus of vagus in gastric function and mucosal damage induced by ethanol in rats.

Experimental evidence indicates that the autonomic nervous system, especially the cholinergic pathway modulates the mucosal defensive mechanism and affects mucosal damage in the stomach. The present study investigated the role of the dorsal motor nucleus of vagus (DMV) in gastric function and its influences on ethanol-induced mucosal damage in pentobarbitone-anesthetized rats. Electrolytic lesion of the DMV as compared with sham operation and lesions of other brain areas, eg, nucleus reticular gigantocellularis and cuneate nucleus, reduced the basal gastric mucosal blood flow (GMBF) and also the blood flow after ethanol administration. The same operation did not affect the acid secretion either in the basal state or during the ethanol treatment period. Lesions at the caudal half of the DMV produced a bigger depression of GMBF when compared with lesion at the rostral half. In the sham-operated rats, ethanol induced severe hemorrhagic lesions in the gastric glandular mucosa, and this was significantly potentiated by lesions at the DMV, especially in the caudal half. The present findings indicate that acute DMV damage at the caudal half markedly affects the GMBF but not the acid secretion. The action on GMBF may contribute to the aggravation of ethanol-induced gastric damage in rats. These data reinforce the idea that the central vagal pathway, especially the caudal half of the DMV, plays a significant role in the modulation of GMBF, which in turn affects the integrity of gastric mucosal barrier.

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.

Acute normovolaemic anaemia prevents ethanol-induced gastric damage in rats through a blood flow related mechanism.

The aim of the study was to assess whether changes in gastric mucosal blood flow induced by acute normovolaemic anaemia influence the susceptibility of the gastric mucosa to ethanol-induced damage, and the relationship of these changes with nitric oxide biosynthesis. Acute normovolaemic anaemia, promoted by exchanging 3 ml of blood by a plasma expander, induced a significant increase in gastric mucosal blood flow measured by hydrogen gas clearance, without changes in arterial blood pressure. After intragastric 60% ethanol administration, gastric blood flow was still significantly higher in anaemic than in control rats, and this was associated with a lower macroscopic and microscopic gastric damage. Following ethanol administration, anaemic rats pretreated with an inhibitor of nitric oxide biosynthesis (L-NMMA, 50 mg/kg, i.v.) had a lower gastric blood flow and a higher macroscopic gastric damage than anaemic rats without pretreatment. Anaemic rats pretreated with vasopressin also had after ethanol administration a lower gastric blood flow and a higher macroscopic gastric damage. It is concluded that acute normovolaemic anaemia protects the gastric mucosa against damage induced by intragastric ethanol. The inhibition of nitric oxide biosynthesis reverts in part this protective effect, and this seems to be related with the capability of nitric oxide to increase gastric mucosal blood flow, since vasoconstriction by a nitric oxide-independent mechanism causes a similar effect.