Ethanol-induced Gastric Damage Research Articles

Ablation of primary afferent neurons by neonatal capsaicin treatment reduces the susceptibility of the portal hypertensive gastric mucosa to ethanol-induced injury in cirrhotic rats

Primary sensory afferent neurons modulate the hyperdynamic circulation in cirrhotic rats with portal hypertension. The stomach of cirrhotic rats is prone to damage induced by ethanol, a phenomenon associated with reduced gastric hyperemic response to acid-back diffusion. The aim of this study was to examine the impact of ablation of capsaicin-sensitive neurons and the tachykinin NK 1 receptor antagonist A5330 on the susceptibility of the portal hypertensive gastric mucosa to ethanol-induced injury and its effects on gastric cyclooxygenase (COX) and nitric oxide synthase (NOS) mRNA expression. Capsaicin was administered to neonatal, male, Wistar rats and the animals were allowed to grow. Cirrhosis was then induced by bile duct ligation in adult rats while controls had sham operation. Ethanol-induced gastric damage was assessed using ex vivo gastric chamber experiments. Gastric blood flow was measured as well as COX/NOS mRNA expression. Topical application of ethanol produced significant gastric damage in cirrhotic rats compared to controls, which was reversed in capsaicin- and A5330-treated animals. Mean arterial and portal pressure was normalized in capsaicin-treated cirrhotic rats. Capsaicin and A5330 administration restored gastric blood flow responses to topical application of ethanol followed by acid in cirrhotic rats. Differential COX and NOS mRNA expression was noted in bile duct ligated rats relative to controls. Capsaicin treatment significantly modified gastric eNOS/iNOS/COX-2 mRNA expression in cirrhotic rats. Capsaicin-sensitive neurons modulate the susceptibility of the portal hypertensive gastric mucosa to injury induced by ethanol via tachykinin NK 1 receptors and signalling of prostaglandin and NO production/release.

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.

Ginseng, the Root of Panax ginseng C.A. Meyer, Protects Ethanol-Induced Gastric Damages in Rat through the Induction of Cytoprotective Heat-Shock Protein 27

Ginseng, the root of Panax ginseng C.A. Meyer, has been reported to exert preventive effects on gastropathy via anti-oxidative and anti-inflammatory actions. In this study, we investigated the protective effects of ginseng against ethanol-induced gastric damages in rat. To examine the preventive effect of ginseng, rats received two different ginseng extracts, A and B, 1 h prior to the administration of ethanol. Pretreatment of rats with ginseng extract A and B attenuated the ethanol-induced gastric lesions by 111 +/- 48 and 142 +/- 47 mm(2) compared to control group (164 +/- 54 mm(2)). Significant induction of cytoprotective heat-shock proteins HSP27 and HSP70 was found in the ginseng-administrated rats, suggesting that the restoration of the proteins might contribute to prevention of ethanol-induced gastric injuries. It is, therefore, suggested that ginseng has a protective effect against ethanol-induced gastric damages by induction of heat-shock proteins 70 and 27.

Protective Effects of the Whisky Congeners on Ethanol‐Induced Gastric Mucosal Damage

The ingestion of both ethanol and whisky can induce acute gastrointestinal bleeding. The effects of the congeners, substances other than ethanol in whisky, on the ethanol-induced gastric mucosal damage were examined in the rat model. After the whisky congeners were intragastrically administered previous to or simultaneous with ethanol ingestion, the gastric damage was macroscopically and microscopically measured. The simultaneous administration of the whisky congeners at a dose of 5 mg/kg body weight, which corresponds to the concentration of congeners contained in whisky, with 50% ethanol did not inhibit the hemorrhagic lesions, but inhibited them at a dose of 150 mg/kg. The treatment with the whisky congeners 30 minutes before the ethanol ingestion prevented the ethanol-induced gastric damage in a dose-dependent manner at 0.5 to 150 mg/kg. The butanol extract of the congeners revealed the strongest prevention compared with the ethyl acetate extract or the water fraction. The administration of indomethacin 60 minutes before the congener treatment partly inhibited the protective effects of the congeners, indicating the partial contribution of prostaglandins in this mechanism. The congeners did not prevent the mucosa by action as a "mild irritant" because the immunohistochemical studies using the antimucin monoclonal antibodies showed that no damage was induced by the administration of the congeners. The present results showed that the whisky congeners have a protective activity against ethanol-induced gastric mucosal injury.

Beneficial effects ofFoeniculum vulgareon ethanol-induced acute gastric mucosal injury in rats

To examine the anti-ulcerogenic and antioxidant effects of aqueous extracts of Foeniculum vulgare (FVE) on ethanol-induced gastric lesions in rats. FVE was administered by gavage at doses of 75, 150 and 300 mg/kg, and famotidine was used at the dose of 20 mg/kg. Following a 60 min period, all the rats were given 1 mL of ethanol (80%) by gavage. One hour after the administration of ethanol, all groups were sacrificed, and the gastric ulcer index was calculated; whole blood malondialdehyde (MDA) and reduced glutathione (GSH), serum nitrate, nitrite, ascorbic acid, retinol and beta-carotene levels were measured in all the groups. It was found that pretreatment with FVE significantly reduced ethanol-induced gastric damage. This effect of FVE was highest and statistically significant in 300 mg/kg group compared with the control (4.18 +/- 2.81 vs 13.15 +/- 4.08, P < 0.001). Also, pretreatment with FVE significantly reduced the MDA levels, while significantly increased GSH, nitrite, nitrate, ascorbic acid, retinol and beta-carotene levels. FVE has clearly a protective effect against ethanol-induced gastric mucosal lesion, and this effect, at least in part, depends upon the reduction in lipid peroxidation and augmentation in the antioxidant activity.

Epidermal growth factor increases tissue antioxidant enzyme activities in ethanol-induced gastric injury in rat

The aim of the present study is to investigate whether the antioxidant mechanisms are involved in epidermal growth factor (EGF)-mediated protection from ethanol-induced gastric damage. Twenty four female Sprague-Dawley rats were assigned into 3 groups; control (C) group (n=8) was given physiologic saline by gavage; ethanol (E) group (n=8) was given 1 ml of 80% ethanol (v/v) in distilled water by gavage and EGF group (n=8) was given EGF (100 mg/kg-body wt.) intraperitonealy half an hour before the administration of ethanol. The protein carbonyl content was significantly higher in the E group than the C group (p<0.01). On the other hand, EGF decreased the protein carbonyl content in the EGF group (p<0.01). Gastric myeloperoxidase activity increased significantly after the administration of ethanol (p<0.01). The administration of EGF decreased significantly the myeloperoxidase activity (p<0.01). Although ethanol caused a slight decrease in the catalase activity, no statistical significance was observed between groups E and C. The catalase activity increased significantly after EGF treatment (p<0.01). The superoxide dismutase activity decreased significantly in the E group when compared to the C group (p<0.05) while it was found to be increased significantly in the EGF group in comparison with the E group (p<0.01). In summary, the present results indicate that the gastroprotective effect of EGF in the experimental lesions induced by ethanol could be attributed to its property such as to augment the antioxidant enzyme activities.

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.

Rate of oxidant stress regulates balance between rat gastric mucosa proliferation and apoptosis

We have characterized an experimental model of ethanol-induced chronic gastritis in which a compensatory mucosal cell proliferation is apparently regulated by lipoperoxidative events. Therefore, the present study is an attempt to further assess the participation of oxidant stress during gastric mucosa proliferation, by administering α-tocopherol (vitamin E) to rats with gastritis. A morphometric analysis was done, and parameters indicative of oxidant stress, cellular proliferation (including cyclin D1 levels), apoptotic events, and activities of endogenous antioxidant systems were measured in gastric mucosa from our experimental groups. After ethanol withdrawal, restitution of surface epithelium coincided with increased lipid peroxidation and cell proliferation and further active apoptosis. High α-tocopherol dosing (100 IU/kg bw) showed a clear antioxidant effect, abolished cell proliferation, and promoted an early and progressive apoptosis, despite vitamin E also enhancing levels of endogenous antioxidants. Indicators of cell proliferation inversely correlated with apoptotic events, and this relationship was blunted by administering vitamin E, probably by affecting translocation of active cyclin D1 into the nucleus. In conclusion, α-tocopherol administration inhibited cell proliferation, leading to a predominance of apoptotic events in ethanol-induced gastric damage. Therefore, the timing and magnitude of lipoperoxidative events seemed to synchronize in vivo cell proliferative and apoptotic events, probably by changing the cell redox state.

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.

Gastric Mucosal Protection via Enhancement of MUC5AC and MUC6 by Geranylgeranylacetone

The mucus layer that covers gastric mucosa is a powerful barrier that protects tissues from the hazardous gastric environment; however, the role of each gastric MUC type, such as MUC1, MUC5AC, and MUC6, has not been evaluated. The purpose of this study is to identify the MUC type, which plays a predominant role in this protective process by use of geranylgeranylacetone (GGA), a promising cytoprotective agent. In addition, the mechanism of mucus secretion promoted by GGA was investigated. Rat gastric mucosal damage was provoked using ethanol, and GGA was pretreated 1 hour before ethanol. GGA was found to significantly protect rats from ethanol-induced gastric damage by increasing mucus levels, MUC5AC and MUC6, especially at ethanol-induced ulcer margins, but not by MUC1. When expression of heat shock protein 70 (HSP70) and neuronal nitric oxide synthase (nNOS) was evaluated by Western blotting, both were found to be increased in GGA-treated ethanol rats. In addition, the cytoprotective effect of GGA was blocked by L-NMMA, a nonspecific NOS inhibitor, but not blocked by aminoguanidine, a specific inducible nitric oxide synthase inhibitor, thus indicating the participation of nNOS. In conclusion, GGA protected ethanol-induced gastric damage by upregulating MUC5AC and MUC6 rather than MUC1. In addition, HSP70 and nNOS were found to be involved in GGA cytoprotection, probably by increasing mucus production or secretion.

Protective effects of green tea polyphenol extracts against ethanol-induced gastric mucosal damages in rats: Stress-responsive transcription factors and MAP kinases as potential targets

There are multiple lines of compelling evidence from epidemiologic and laboratory studies supporting that frequent consumption of green tea is inversely associated with the risk of chronic human diseases including cancer. The chemopreventive and chemoprotective effects of green tea have been largely attributed to antioxidative and anti-inflammatory activities of its polyphenolic constituents, such as epigallocatechin gallate. The present study was designed to evaluate the efficacy of green tea polyphenols in protecting against alcohol-induced gastric damage and to elucidate the underlying mechanisms. Intragastric administration of ethanol to male Sprague–Dawley rats caused significant gastric mucosal damage, which was accompanied by elevated expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as well as transient activation of redox-sensitive transcription factors, such as NF-κB and AP-1, and mitogen-activated protein kinases (MAPKs). Oral administration of the green tea polyphenolic extract (GTE) significantly ameliorated mucosal damages induced by ethanol and also attenuated the ethanol-induced expression of COX-2 and iNOS. Inactivation of MAPKs, especially p38 and ERKl/2, by GTE might be responsible for inhibition of ethanol-induced expression of COX-2 and iNOS.

The protective effect of thymoquinone on ethanol-induced acute gastric damage in the rat

Previous studies have indicated a pivotal role of reactive oxygen species in the pathomechanism of gastric ulcer. Recent studies demonstrated that thymoquinone (TQ) had an antioxidant effect on injuries caused by various toxic agents in different experimental models. The present study was planned to test whether TQ, the main constituent of the volatile oil of Nigella sativa seeds, was capable to exert beneficial effects on acute gastric ulcer model in rats. We examined antiulcerative and antioxidant effects of TQ on ethanol (EtOH)-induced gastric lesions in rats. The data we collected showed that gastric ulcer caused by absolute EtOH induction resulted in an increase in lipid peroxidation, represented by malondialdehyde level as well as by superoxide dismutase level, an antioxidant enzyme, whereas it resulted in a decrease in glutathione content in rat stomach tissue. Thymoquinone (20 mg/kg) administration reduced the ulcer index and the malondialdehyde level, and reversed the glutathione depletion. However, it did not statistically change the high superoxide dismutase activity induced by EtOH. These results suggest that TQ could inhibit the development of EtOH-induced gastric ulcer, and gastroprotective action of TQ might be in part dependent on its antioxidant property.

Effects of hexarelin against acid-independent and acid-dependent ulcerogens in the rat

The effects of intracerebroventricular (icv) or subcutaneous (sc) hexarelin (Hexa) administration, against gastric ulcers induced by ethanol (50%, 1 ml/rat/os) or Indomethacin (20 mg/kg/os) were examined in conscious rats. Hexa at 1 nmol/rat, icv or 10 nmol/kg, sc reduced ethanol-induced ulcers by 47% and 32% respectively. Hexa, but not ghrelin significantly worsened (+40%) Indomethacin-induced ulcers when injected sc. Hexa-gastroprotection against ethanol-induced ulcers was removed by the GHS-R antagonist ( d-Lys 3)-GRPR-6 and by the inhibitor of NO-synthase (NOS) N ω-nitro- l-arginine methyl ester. Semiquantitative RT-PCR assay of gastric NOS mRNA isoforms revealed that the reduction in iNOS-derived NO and the increase of constitutive-derived NO are relevant for the gastroprotection of Hexa against ethanol-induced gastric damage.

PROTECTIVE EFFECTS OF QUERCETIN, A FLAVONOID ANTIOXIDANT, IN ABSOLUTE ETHANOL-INDUCED ACUT GASTRIC ULCER

Free radicals have been reported to be responsible for many ailments including gastroduodenal ulcers. Recent studies demonstrated that quercetin (QE) has an antioxidant effects on injuries caused by various toxic agents in different experimental models. In our study, we examined anti-ulcerogen and antioxidant effects of quercetin on ethanol-induced gastric lesions in rats. QE was administered intraperitoneally (i.p.) 50 mg/kg. It was found that pretreatment with QE significantly reduced ethanol-induced gastric damage and malondialdehyde levels, and significantly increased antioxidant enzyme activities. We conclude that QE clearly has antioxidant properties and that the protective effect of QE against ethanol-induced gastric mucosal lesion, at least in part, depends upon the reduction in the lipid peroxidation and an increase in the activity of antioxidant enzymes.

Preventive effect of the flavonoid, wogonin, against ethanol-induced gastric mucosal damage in rats.

Whether wogonin (5,7-dihydroxy-8-methoxyflavone), a flavonoid originated from the root of Scutellaria baicalensis Georgi, which has been shown to have antiinflammatory and antitumor activities in various cell types, possesses a gastric cytoprotective effect was investigated in an ethanol-induced gastric damage model in rats. Ethanol administration alone induced evident gastric damage including gastric hemorrhages and edema, while this gastric damage was significantly attenuated by wogonin pretreatment (30 mg/kg B.W.) 1 hr before ethanol administration. As major protective mechanisms of wogonin on ethanol-induced gastric damage, we found that wogonin showed either antiinflammatory effects through dual actions on arachidonic acid metabolism, i.e., induction of prostaglandin D2 and suppression of 5S-hydroxyeicosatetraenoic acid (5S-HETE), or preventive induction of profuse apoptosis in the stomach. Conclusively, the flavonoid wogonin could be used as a preventive agent of alcohol-induced gastropathy, whose actions were proven to be strong antiinflammation and apoptosis induction.

Study of Mimusops elengi bark in experimental gastric ulcers

The present study was designed to investigate the effect of Mimusops elengi (Sapotaceae) against experimental gastric ulcers. The 50% alcoholic extract of Mimusops elengi (Ext E) and its different fractions namely ethyl acetate (Ext E 1), n-butanol (Ext E 2), methanol (Ext E 3) and aqueous (Ext E 4) were studied (p.o.) against ethanol-induced gastric damage. Ext E 1 was also studied in ethanol-induced, pylorus-ligated and water-immersion plus stress-induced gastric ulcer models. Ranitidine HCl (80 mg kg −1) was used as a reference standard. In ethanol-induced gastric ulcer model, pantoprazole (20 mg kg −1) was also used as a reference standard. Ext E 1 tested in mice up to the dose of 5000 mg kg −1 (p.o.) did not produce any sign of toxicity. Ext E at the doses of 50, 100, 300 and 500 mg kg −1 and its different fractions (100 mg kg −1) showed reduction in gastric ulceration ( P<0.05). Ext E 1 at the doses of 10, 50 and 100 mg kg −1 showed dose-dependent inhibition of gastric lesions against ethanol-induced gastric damage. In 19 h pylorus-ligated animals, Ext E 1 at 50 and 100 mg kg −1 doses showed significant reduction in ulcer index ( P<0.05). Significant reduction was also observed in total acidity, volume of gastric acid secretion, total acid output and pepsin activity ( P<0.05) when compared with the control group. Besides, Ext E 1 showed increase in the mucosal glycoproteins that was evident from significant rise in total carbohydrates to protein ratio (TC:PR ratio) ( P<0.05), which is an indication of mucin activity. Ext E 1 also showed protection against water-immersion plus stress-induced gastric lesions that was evident from dose-dependent decrease in ulcer index ( P<0.05), score for intensity ( P<0.05) and total lesion area ( P<0.05) when compared with the control group. It can be concluded from our study that Ext E 1 possesses anti-ulcer activity against experimental gastric ulcers. The mechanism of anti-ulcer activity can be attributed to decrease in gastric acid secretory activity along with strengthening of mucosal defensive mechanisms.

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.

Antioxidative activity and protective effect against ethanol-induced gastric mucosal damage of a potato protein hydrolysate.

Antioxidative activity and protective effect against ethanol-induced gastric mucosal damage of potato protein hydrolysate (potato peptides, Po-P) were studied in vitro and in vivo. The Po-P obtained by proteolysis with Amano P and pancreatin inhibited linoleic acid oxidation either by 83%, at its coexistent 0.005% in a ferric thiocyanate assay system or by 32% at its coexistent 0.0002% in a beta-carotene decolorization assay system. Meanwhile Po-P were orally administered to male Wistar rats at doses of 12.5-100 mg/kg of body weight (BW) 30 min prior to ethanol injection. Consequently the ethanol-induced gastric damage was significantly reduced in a dose-dependent manner in the Po-P administered rat. The highest effect was observed in the group dosed with 100 mg Po-P/kg BW; the inhibition ratio was 69.6%. The extent of antioxidation or protection against ethanol-induced gastritis was quite similar to those of the respective peptides from casein, corn protein and ovalbumin, suggesting that the potato protein hydrolysate could serve as a useful food ingredient in practical eating habits.

Mechanism of the beneficial effects of dantrolene sodium on ethanol-induced acute gastric mucosal injury in rats

In our study, we examined anti-ulcerogen and antioxidant effects of dantrolene sodium on ethanol-induced gastric lesions in rats. Dantrolene sodium was administered intraperitoneally (i.p.) in several doses, and famotidine was used at a dose of 20 mg kg −1. It was found that pretreatment with dantrolene sodium at doses of 1, 5 and 10 mg kg−1 significantly reduced ethanol-induced gastric damage and malondialdehyde levels, and significantly increased antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. We conclude that dantrolene sodium clearly has antioxidant properties and that the protective effect of dantrolene sodium against ethanol-induced gastric mucosal lesion, at least in part, depends upon the reduction in the lipid peroxidation and an increase in the activity of antioxidant enzymes SOD and GSH-Px.