Ethanol-induced Gastric Damage Research Articles

Endothelin and neonatal capsaicin regulate gastric resistance to injury in BDL rats

To investigate the relationship between primary afferent neurons, endothelin (ET) and the role of its receptors on ethanol-induced gastric damage in cirrhotic rats. Cirrhosis and portal hypertension were induced in rats by bile duct ligation (BDL) while controls had a sham operation. The association between ET and afferent neurons on the gastric mucosa was evaluated by capsaicin treatment in newborn rats, the use of ET agonists or antagonists, gastric ET-1 and -3 mRNA and synthetic capacity. Ethanol-induced damage was assessed using ex vivo gastric chamber experiments. Gastric blood flow was measured by laser-Doppler flowmetry. ET-3 and an ET(B) receptor antagonist significantly reduced the extent of ethanol-induced gastric damage in BDL rats. Gastric ET-1 and -3 levels were 30% higher in BDL rats compared to control rats. Capsaicin treatment restored the gastric resistance and blood flow responses to topical application of ethanol in BDL rats and ET-1 and -3 production to levels observed in controls. Our results suggest that the reduced resistance of the gastric mucosa of cirrhotic rats to ethanol-induced injury is a phenomenon modulated by ET through the ET(B) receptor and by sensory afferent neurons.

Gastroprotective potentials of the methanolic extract of Garcinia kola in rats

Background : There is a claim in the folklore medicine of the use of Garcinia kola (GK) seeds in the management of gastritis and gastric ulcer. However, there has not been any scientific evidence in the literature that substantiated or refuted this with regards to the management of gastritis and gastric ulcerations in association with gastric morphological damage and cytoarchitectural changes. Aim : This study aims at evaluating the efficacy of the methanolic extract of GK (mGK) in the management of gastritis and gastric ulcerations in rat model. Methods : Adult albino rats with comparable weight were randomized into six groups. Group A was administered 1ml/kg bw of distilled water three times daily. Group B and C were administered ethanol (0.2ml/23g bw of 80% v/v) two hours prior termination of experiment and 150mg/kg bw of mGK daily for three weeks respectively. Group D was pre-treated with mGK and then ethanol as in groups B and C. Group E was administered ethanol as in group B and posttreated with mGK as in group C. Group F was concomitantly treated with mGk as in group C and ethanol as in group B. Results : Ethanol induced gastritis and gastric ulceration. Treatment with mGK abrogated ethanolinduced gastric damage: it reduced the morphological damage score, ulcer score, gastric wall thickness, and lipid peroxidation (p Conclusion : This study substantiated the gastroprotective potentials of mGK. The mechanism of action could be associated with the anti-oxidative activities of the flavonoid constituents. Keywords : Garcinia kola , flavonoids, gastritis, ulcer, lipid peroxidation

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.

Sulfated-Polysaccharide Fraction from Red Algae Gracilaria caudata Protects Mice Gut Against Ethanol-Induced Damage

The aim of the present study was to investigate the gastroprotective activity of a sulfated-polysaccharide (PLS) fraction extracted from the marine red algae Gracilaria caudata and the mechanism underlying the gastroprotective activity. Male Swiss mice were treated with PLS (3, 10, 30 and 90 mg·kg−1, p.o.), and after 30 min, they were administered 50% ethanol (0.5 mL/25 g−1, p.o.). One hour later, gastric damage was measured using a planimeter. Samples of the stomach tissue were also obtained for histopathological assessment and for assays of glutathione (GSH) and malondialdehyde (MDA). Other groups were pretreated with l-NAME (10 mg·kg−1, i.p.), dl-propargylglycine (PAG, 50 mg·kg−1, p.o.) or glibenclamide (5 mg·kg−1, i.p.). After 1 h, PLS (30 mg·kg−1, p.o.) was administered. After 30 min, ethanol 50% was administered (0.5 mL/25g−1, p.o.), followed by sacrifice after 60 min. PLS prevented-ethanol-induced macroscopic and microscopic gastric injury in a dose-dependent manner. However, treatment with l-NAME or glibenclamide reversed this gastroprotective effect. Administration of propargylglycine did not influence the effect of PLS. Our results suggest that PLS has a protective effect against ethanol-induced gastric damage in mice via activation of the NO/KATP pathway.

Strawberry Polyphenols Attenuate Ethanol-Induced Gastric Lesions in Rats by Activation of Antioxidant Enzymes and Attenuation of MDA Increase

Background and AimFree radicals are implicated in the aetiology of gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. Strawberries are common and important fruit due to their high content of essential nutrient and beneficial phytochemicals which seem to have relevant biological activity on human health. In the present study we investigated the antioxidant and protective effects of three strawberry extracts against ethanol-induced gastric mucosa damage in an experimental in vivo model and to test whether strawberry extracts affect antioxidant enzyme activities in gastric mucosa.Methods/Principal FindingsStrawberry extracts were obtained from Adria, Sveva and Alba cultivars. Total antioxidant capacity and radical scavenging capacity were performed by TEAC, ORAC and electron paramagnetic resonance assays. Identification and quantification of anthocyanins was carried out by HPLC-DAD-MS analyses. Different groups of animals received 40 mg/day/kg body weight of strawberry crude extracts for 10 days. Gastric damage was induced by ethanol. The ulcer index was calculated together with the determination of catalase and SOD activities and MDA contents. Strawberry extracts are rich in anthocyanins and present important antioxidant capacity. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious role. Antioxidant enzyme activities increased significantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found.ConclusionsStrawberry extracts prevented exogenous ethanol-induced damage to rats' gastric mucosa. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity of promoting the action of antioxidant enzymes. A diet rich in strawberries might exert a beneficial effect in the prevention of gastric diseases related to generation of reactive oxygen species.

In vivo anti-inflammatory effect of Rosa canina L. extract

Ethnopharmacological relevanceRosa canina L. is a medicinal plant largely used in traditional folk medicine. Several compounds from rose hip extracts were reported to display in vitro anti-inflammatory activities. Aim of the studyThe in vivo effects of Rosa canina extracts are still poorly investigated. In the present study the anti-inflammatory and the gastroprotective effects of a hydroalcoholic crude extract of Rosa canina fruits were tested in rat. Materials and methodsThe anti-inflammatory activity of the extract was tested on the carrageenin-induced rat paw edema assay. The gastroprotective effect was investigated on the ethanol-induced gastric damage model. The in vitro antioxidant activity of this extract was also quantified using the Briggs–Rauscher oscillating reaction, the Trolox Equivalent Antioxidant Capacity method, and the Total Phenolic Content. ResultsData show that the Rosa canina extract inhibits the development of carrageenin-induced edema; the anti-inflammatory power is similar to that of indomethacin. The antiedema effect was more significant using a higher dose of the extract. The total score expressing gastric damage was lower in Rosa canina pre-treated stomachs with respect to unpre-treated ones, although the antiulcerogenic effectiveness was not statistically significant. The antiulcerogenic effectiveness was not statistically detectable, even if the total score expressing gastric damage was lower in Rosa canina stomachs from pre-treated rats with respect to unpre-treated ones. Chemical analysis revealed that the extract owns a good antioxidant activity that may also contribute to the anti-inflammatory effects observed in vivo. ConclusionsAltogether, the present data demonstrate the anti-inflammatory property of Rosa canina suggesting its potential role as adjuvant therapeutic tool for the management of inflammatory-related diseases.

Protection by almagate of ethanol-induced gastric mucosal damage in rats.

The study was designed to analyse the protective effects of almagate on a model of gastric injury, ethanol-induced mucosal damage, in which acid plays little, if any, role. Pretreatment with almagate dose-dependently reduced the level of gastric damage induced by oral administration of 1 mL 100% ethanol. Administration of 12 mumol kg-1 alamagate 30 min before ethanol significantly reduced the area of mucosal damage by 65 +/- 10%, and the maximum level of inhibition (74 +/- 11%) was obtained with 150 mumol kg-1 almagate. Administration of higher doses of almagate (200-250 mumol kg-1) did not result in any further increase in the level of protection against ethanol-induced gastric damage. Administration of 1 mL 100% ethanol induces substantial damage to the gastric mucosa, with nearly 40% of the length of the section evaluated exhibiting deep necrotic and haemorrhagic damage. Pretreatment with almagate caused a significant diminution in all parameters of histological damage, whereas damage to the epithelial cell layer was only significantly reduced by pretreatment with the highest doses evaluated (25, 50 and 150 mumol kg-1). Administration of aluminium hydroxide did not modify ethanol-induced mucosal damage, even at doses containing concentrations of aluminium higher than those present in gastroprotective doses of almagate. Pretreatment with sucralfate, another aluminium containing compound, at doses of 250 mumol kg-1 protected the mucosa, although lower doses did not. The present study has shown that almagate prevents ethanol-induced gastric mucosal damage.(ABSTRACT TRUNCATED AT 250 WORDS)

The cytoprotective effect of zinc L-carnosine on ethanol-induced gastric gland damage in rabbits.

The effects of zinc L-carnosine on the damaging actions of ethanol were examined in rabbit isolated gastric glands. Ethanol (8%, v/v) incubation produced a 50% viability of the gland populations and released a significant amount (38%) of the total lactate dehydrogenase (an index of membrane injury) of the glands. Zinc L-carnosine pre-incubation for 15 min markedly prevented these actions of ethanol; however, L-carnosine by itself did not have these effects. The findings indicate that zinc ion but not carnosine in the zinc L-carnosine molecule possesses cytoprotective action against ethanol-induced gastric gland damage in rabbits.

The vagus nerve and its non-cholinergic mechanism in the modulation of ethanol-induced gastric mucosal damage in rats.

The role of the cholinergic pathway in the vagus nerve in modulating gastric lesion formation by ethanol was examined, using an ex-vivo stomach chamber preparation. Subdiaphragmatic vagotomy significantly increased the lesion areas but lowered acid secretion and gastric mucosal blood flow (GMBF). Atropine had no effect, whereas pirenzepine antagonized ethanol-induced mucosal damage. All three procedures showed similar potencies in depressing acid secretion, but only pirenzepine reversed the fall in the GMBF produced by ethanol. These differential effects of vagotomy, atropine and pirenzepine on gastric function suggest that the cholinergic component in the vagus nerve may not be important in the formation of ethanol-induced gastric damage. The persistent protective action as well as the restoration of ethanol-induced GMBF drop by pirenzepine in vagotomized animals further support this hypothesis. The worsening effect of vagotomy is probably modulated by a non-cholinergic mechanism, the abolition of which makes the gastric mucosa more susceptible to damage by ethanol. The acid-independent protective action of pirenzepine and its influence on the GMBF, which were not exhibited by atropine, are indeed unique and perhaps may be attributed to this non-cholinergic pathway.

Polymer fraction of Aloe vera exhibits a protective activity on ethanol-induced gastric lesions

For centuries, Aloe has been used as a herbal plant remedy against skin disorders, diabetes, and for its cardiac stimulatory activity. Here, we examined the gastroprotective effects of an Aloe vera polymer fraction (Avpf; molecular weight cut-off ≥50 kDa; 150 mg/kg body weight, p.o.) on an ethanol-induced gastric lesion mouse model. Mice pre-treated with Avpf had significantly fewer gastric lesions than their respective controls. To further examine the potential mechanism underlying this effect, we used reverse transcription-polymerase chain reaction to examine nitric oxide synthase and matrix metalloproteinase (MMP)mRNA expression on tissues from gastric lesions. Our results revealed that the mRNA expressions of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS) were each reduced by ~50% in Avpf-treated mice vs. the controls, whereas, the mRNA expression levels of endothelial nitric oxide synthase remained unchanged. MMP-9, an index for gastric lesions, also alleviated the ethanol-treated gastric ulceration during Avpf treatment. These findings collectively suggest that Avpf significantly protects the gastric mucosa against ethanol-induced gastric damage, at least in part, by decreasing mRNA expression levels of not only iNOS and nNOS, but also MMP-9.

Anti-ulcer activity of Cyrtocarpa procera analogous to that of Amphipterygium adstringens, both assayed on the experimental gastric injury in rats

The bark of Amphipterygium adstringens (Aa) is commonly mixed or adulterated with the bark of Cyrtocarpa procera (Cp) and sold in Mexican markets. Aa is a well known species in Mexico used as decoction to relieve ulcers. Scientific reports reinforcing the anti-ulcer activity of Aa have been previously described, but those describing the anti-ulcer properties of Cp as a substitute for Aa in folk medicine are scarce. To investigate anatomical and phytochemical differences between these species, as well as to assess the anti-ulcer effect of Cp extracts in comparison to the Aa extracts. Anatomical micro-technique and physical and spectroscopic data were used to analyze differences between Cp and Aa. Regard to the pharmacological activity, it was assessed by using the ethanol-induced gastric damage model in rats. Whereas the bark anatomy of Aa was characterized by vertical canals in the periderm and the rare occurrence of fibers in its phloem, a periderm without vertical canals and abundant fibers in the phloem were distinctive features of Cp. Phytochemical analysis allowed the identification of tirucallane, masticadienonic and 3α-hydroxymasticadienonic acids as major components in Aa, while β-amyrin and β-sitosterol were obtained from Cp. Gastric lesions observed in the control group decreased in the presence of 100mg/kg of hexane, ethyl acetate and methanol extracts from the normal or regenerated bark of Cp, thus resembling the anti-ulcer effect of Aa. Nevertheless, major anti-ulcer potency was observed with the most active methanol extract from Cp obtained from normal [the effective dose fifty ED(50)=45.54 mg/kg] or regenerated (ED(50)=36.68 mg/kg) bark in comparison to Aa (ED(50)=115.64 mg/kg). Chemical and anatomical differences were found between these species, but since the anti-ulcer activity of Cp is similar to that shown by Aa our results reinforce the use of both species for the relief of gastric ulcer in folk medicine.

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.

Gastroprotective effect of heme-oxygenase 1/biliverdin/CO pathway in ethanol-induced gastric damage in mice

Our objective was to evaluate the role of heme-oxygenase 1 (HO-1)/biliverdin/CO pathway in gastric defense against ethanol-induced gastric damage in mice. Mice were pre-treated with saline, hemin (HO-1 inducer), biliverdin (HO-1 product), dimanganese decacarbonyl (DMDC, CO donor) or zinc protoporphyrin IX (ZnPP IX, HO-1 antagonist). Another group received soluble guanylate cyclase (sGC) inhibitor (ODQ) 30 min before hemin, biliverdin or DMDC. After 30 min, gastric damage was induced by ethanol. After one hour, rats were sacrificed. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malonylaldehyde (MDA), glutathione (GSH) or bilirubin. HO-1 expression was determined after saline or ethanol administration by polymerase chain reaction (PCR) or immunohistochemistry. Ethanol (25% or 50%) induced gastric damage, increased MDA levels and reduced GSH in the gastric tissue. Ethanol 50% increased HO-1 mRNA transcripts, HO-1 immunoreactivity, and bilirubin concentration in gastric mucosa. Pre-treatment with hemin reduced gastric damage and MDA formation and increased GSH concentration in the gastric mucosa. ZnPP IX amplified the ethanol-induced gastric lesion, increased MDA formation and decreased GSH concentration in gastric mucosa. Biliverdin and DMDC reduced gastric damage and MDA formation and increased GSH concentration in the gastric tissue. ODQ completely abolished the DMDC protective gastric effect. However, effects of hemin or biliverdin did not change with ODQ treatment. Our results suggest that HO-1/biliverdin/CO pathway plays a protective role against ethanol-induced gastric damage through mechanisms that can be dependent (CO) or independent (biliverdin) of sGC activation.

Bioactivity of Sesquiterpenes: Compounds that Protect from Alcohol-Induced Gastric Mucosal Lesions and Oxidative Damage

Sesquiterpene lactones of the guaianolide and eudermanolide types are considered of interest because they have an effect in the regulation and prevention of oxidative damage and inflammation-mediated biological damage. Dehydroleucodine, a natural sesquiterpene isolated from Artemisia douglasiana Besser, and ilicic aldehyde, a semi-synthetic sesquiterpene lactones, showed in vivo protection in ethanol-induced gastric mucosa damage. This action was determined by in situ gastric mucosa chemiluminescence and by tissue antioxidant content.

Inhibition of endogenous hydrogen sulfide synthesis by PAG protects against ethanol-induced gastric damage in the rat

Hydrogen sulfide (H(2)S) is a gaseous mediator involved in a multitude of physiological functions; however the role of H(2)S in the gut is far from being understood completely. The aim of this study was to determine the effect of d-l-propargylglycine (PAG), an inhibitor of H(2)S synthesis, on ethanol-induced gastric injury in rat and to examine the role of l-cysteine, exogenous H(2)S, prostaglandins, non-protein sulphydryls groups, nitric oxide and K(ATP) channels in the gastroprotective effect of PAG. Administration of PAG (3.12 to 75mg/kg i.p.) or l-cysteine (0.3 to 300mg/kg, p.o.) exhibited a dose-dependent protective effect after intragastric administration of 1ml of ethanol to induce gastric injury. The gastroprotective effect of PAG (25mg/kg i.p.) was maintained after post-treatment with l-cysteine (10mg/kg p.o.), while NaHS (8.4mg/kg p.o.) inhibited this effect. The levels of gastric hydrogen sulfide were increased after ethanol-induced gastric damage and they were reverted by PAG while prostaglandin E(2) levels in gastric tissue were decreased by ethanol and PAG did not revert to this effect. Pretreatment with indomethacin (10mg/kg i.p.) and N-ethylmaleimide (NEM, 10mg/kg s.c.) resulted in a reversion of the gastroprotective effect of PAG while N(G)-nitro-l-arginine methyl ester (L-NAME, 70mg/kg s.c.), glibenclamide (1mg/kg i.p.) or diazoxide (3mg/kg i.p.) did not induce any changes. These results suggest that ethanol-induced gastric injury is related with an increment of endogenous H(2)S levels, and therefore a decrement of H(2)S levels by PAG is a benefit to protect gastric injury caused by ethanol.

Protective effect of anacardic acids from cashew (Anacardium occidentale) on ethanol-induced gastric damage in mice

Cashew nut-shell liquid and the contained anacardic acids (AAs) have been shown to possess antioxidant, lipoxygenase inhibitory, anti-Helicobacter pylori and antitumor properties. Despite these known effects, hitherto there were no published reports on their likely gastroprotective effects. The present study was designed to verify whether AAs afford gastroprotection against the ethanol-induced gastric damage and to examine the underlying mechanism(s). Gastric damage was induced by intragastric administration of 0.2mL of ethanol (96%). Mice in groups were pretreated orally with AAs (10, 30 and 100mg/kg), misoprostol (50 microg/kg), or vehicle (2% Tween 80 in saline, 10mL/kg), 45min before ethanol administration. They were sacrificed 30min later, the stomachs excised, and the mucosal lesion area (mm(2)) measured by planimetry. Gastroprotection was assessed in relation to inhibition of gastric lesion area. To study the gastroprotective mechanism(s), its relations to capsaicin-sensitive fibers, endogenous prostaglandins, nitric oxide and ATP-sensitive potassium channels were analysed. Treatments effects on ethanol-associated oxidative stress markers GSH, MDA, catalase, SOD, and total nitrate/nitrite levels as an index of NO were measured in gastric tissue. Besides, the effects of AAs on gastric secretory volume and total acidity were analysed in 4-h pylorus-ligated rat. AAs afforded a dose-related gastroprotection against the ethanol damage and further prevented the ethanol-induced changes in the levels of GSH, MDA, catalase, SOD and nitrate/nitrite. However, they failed to modify the gastric secretion or the total acidity. It was observed that the gastroprotection by AAs was greatly reduced in animals pretreated with capsazepine, indomethacin, l-NAME or glibenclamide. These results suggest that AAs afford gastroprotection principally through an antioxidant mechanism. Other complementary mechanisms include the activation of capsaicin-sensitive gastric afferents, stimulation of endogenous prostaglandins and nitric oxide, and opening of K(+)(ATP) channels. These combined effects are likely to be accompanied by an increase in gastric microcirculation.

Protective effect of a polysaccharide from Hizikia fusiformis against ethanol-induced cytotoxicity in IEC-6 cells

In the present study, we examined the signaling pathways related to the ethanol-protective effect of Hf-PS-1 in IEC-6 cells. Ethanol induced the death of IEC-6 cells in a dose-dependent manner, and pretreatment with Hf-PS-1 abrogated the ethanol toxicity. When we examined whether the effect of Hf-PS-1 on ethanol cytotoxicity was associated with insulin growth factor-I receptor signaling pathways, involving mitogen-activated protein kinase (MAPK), we found that ethanol treatment decreased the phosphorylation of Shc and the binding of Grb2 to Shc, and Hf-PS-1 pretreatment increased them. Ethanol treatment also induced the phosphorylation of JNK and ERK, whereas Hf-PS-1 pretreatment decreased JNK activation but not ERK activation. Using a JNK inhibitor (SP600125), we examined GSH levels to determine whether Hf-PS-1 pretreatment mi20 ght protect against ethanol-induced gastric intestinal damage by down-regulating JNK. Co-treatment with SP600125 and ethanol decreased GSH levels, indicating that JNK phosphorylation is a critical factor during ethanol-induced injury and that the effect of Hf-PS-1 occurs via JNK down-regulation. We have thus demonstrated the protective effect of Hf-PS-1 against ethanol-induced cellular damage. Therefore, Hf-PS-1 may be useful as a bio-functional food source to protect against ethanol-induced gastrointestinal injury.

Gastroprotective effect of lupeol on ethanol-induced gastric damage and the underlying mechanism

The effect of lupeol, a natural pentacyclic triterpene on ethanol-induced gastric damage in mice was evaluated. The gastroprotection was assessed by determination of changes in mean gastric lesion area, quantification of mucosal non-protein sulfhydryls (NP-SH), and characterized using drugs that influence the endogenous prostaglandins, alpha(2)-adrenoceptors, nitric oxide, K(ATP)-channels, and intracellular calcium. Orally administered lupeol (3, 10, and 30 mg/kg) significantly and dose-dependently attenuated the ethanol-induced gastric damage by 39-69%, whereas the positive control N-acetylcysteine (NAC, 300 mg/kg, i.p.) afforded 32% protection. Both lupeol and NAC restored the NP-SH depleted by ethanol but the lupeol effect was only marginal. Lupeol gastroprotection was attenuated by indomethacin and L-NAME, the respective COX and NO-synthase inhibitors and was weakly sensitive to alpha(2)-adrenergic antagonist yohimbine and K(ATP)-channel blocker glibenclamide, but more profoundly to calcium blocker verapamil. These pharmacological effects of lupeol may synergistically contribute to alleviating the ethanol-associated gastric damage, which is multifactorial.

Hydrogen Sulfide Prevents Ethanol-Induced Gastric Damage in Mice: Role of ATP-Sensitive Potassium Channels and Capsaicin-Sensitive Primary Afferent Neurons

The aim of this study was to evaluate the protective effect of hydrogen sulfide (H(2)S) on ethanol-induced gastric lesions in mice and the influence of ATP-sensitive potassium (K(ATP)) channels, capsaicin-sensitive sensory afferent neurons, and transient receptor potential vanilloid (TRPV) 1 receptors on such an effect. Saline and L-cysteine alone or with propargylglycine, sodium hydrogen sulfide (NaHS), or Lawesson's reagent were administrated for testing purposes. For other experiments, mice were pretreated with glibenclamide, neurotoxic doses of capsaicin, or capsazepine. Afterward, mice received L-cysteine, NaHS, or Lawesson's reagent. After 30 min, 50% ethanol was administrated by gavage. After 1 h, mice were sacrificed, and gastric damage was evaluated by macroscopic and microscopic analyses. L-cysteine, NaHS, and Lawesson's reagent treatment prevented ethanol-induced macroscopic and microscopic gastric damage in a dose-dependent manner. Administration of propargylglycine, an inhibitor of endogenous H(2)S synthesis, reversed gastric protection induced by L-cysteine. Glibenclamide reversed L-cysteine, NaHS, or Lawesson's reagent gastroprotective effects against ethanol-induced macroscopic damage in a dose-dependent manner. Chemical ablation of sensory afferent neurons by capsaicin reversed gastroprotective effects of L-cysteine or H(2)S donors (NaHS or Lawesson's reagent) in ethanol-induced macroscopic gastric damage. Likewise, in the presence of the TRPV1 antagonist capsazepine, the gastroprotective effects of L-cysteine, NaHS, or Lawesson's reagent were also abolished. Our results suggest that H(2)S prevents ethanol-induced gastric damage. Although there are many mechanisms through which this effect can occur, our data support the hypothesis that the activation of K(ATP) channels and afferent neurons/TRPV1 receptors is of primary importance.

Ulcer preventive and antioxidative properties of astaxanthin from Haematococcus pluvialis

The anti-ulcer properties of astaxanthin fractions such as total carotenoid and astaxanthin esters from Haematococcus pluvialis were evaluated in ethanol-induced gastric ulcers in rats. Since oxygen radical release is a pathogenic factor of ethanol-induced gastric damage, astaxanthin — a free radical scavenger, was investigated as a potential ulcer preventive agent. Astaxanthin fractions — total carotenoid and astaxanthin esters were orally administered to experimental rats at 100, 250 and 500 μg/kg b.w. prior to ulcer induction. Alcian blue binding assay indicates that, total carotenoid and astaxanthin esters at 500 μg/kg b.w could protect gastric mucin ~ 40% and 67% respectively. Pre-treatment with astaxanthin esters, also resulted in significant increase in antioxidant enzyme levels — catalase, superoxide dismutase, and glutathione peroxidase in stomach homogenate. Histopathological examination substantiated the protective effect of astaxanthin in pre-treated rats. The increased antioxidant potencies such as free radical scavenging activity with an IC 50 of ~ 8 μg/ml and reducing power abilities (59 × 10 3 U/g) in vitro, reveal that H. pluvialis astaxanthin may protect gastric mucosal injury by antioxidative mechanism. In addition, ~ 23 fold increased lipoxygenase-inhibitory property, in comparison with standard astaxanthin and significant H +, K +-ATPase-inhibitory activity of astaxanthin esters, in comparison with known proton pump blocking anti-ulcer drug — omeprazole, may envisage the potential gastroprotective effect by regulating the gastric mucosal injury and gastric acid secretion by the gastric cell during ulcer disease.