Ethanol-induced Gastric Injury Research Articles

Chungpihongsim radish (Raphanus sativus L. cv. Chungpihongsim) ameliorates ethanol-induced gastric injury in rats

We evaluated whether crude juice extract of chungpihongsim radish (Raphanus sativus L. cv. Chungpihongsim) (CH radish), with its characteristic red flesh and white skin, ameliorated ethanol-induced gastric injury in rats. Animals were divided into five groups: normal control, a group given CH radish extract (1000 mg/kg) only, two groups orally administered CH radish extract (500 and 1000 mg/kg, respectively, daily for 2 weeks) with ethanol treatment (5 mL/kg) 24 h after final administration of CH radish extract, and a group treated with ethanol alone. Tissues of stomach were collected after sacrifice, and the gastric mucosal injury index using hemorrhagic lesions were measured. Lipid peroxidation was evaluated based on malondialdehyde concentration. The radical-scavenging enzymes superoxide dismutase (SOD) and catalase (CAT) were also measured. Rats treated with CH radish extract (500 or 1000 mg/kg) for 2 weeks experienced no change in body weight. Pretreatment with the extract at both doses significantly ameliorated ethanol-induced hemorrhagic lesions in the gastric mucosa (p < 0.05), decreased malondialdehyde concentration (p < 0.05), and increased the levels of SOD (p < 0.05) and CAT (p < 0.05), compared to ethanol-alone treatment. These findings suggest that pretreatment with CH radish extract reduces ethanol-induced damage in the gastric mucosa, mediated partly by a decrease in lipid peroxidation and an increase in the cytoprotective radical-scavenging enzymes SOD and CAT.

Anti-Ulcerogenic Properties of Lycium chinense Mill Extracts against Ethanol-Induced Acute Gastric Lesion in Animal Models and Its Active Constituents.

The objective of this study was to explore the gastroprotective properties of the aerial part of Lycium chinense Mill (LCA) against ethanol-induced gastric mucosa lesions in mice models. Administration of LCA at doses of 50, 100, 200 and 400 mg/kg body weight prior to ethanol consumption dose dependently inhibited gastric ulcers. The gastric mucosal injury was analyzed by gastric juice acidity, glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), myeloperoxidase (MPO) activities. Furthermore, the levels of the inflammatory mediators, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in serum were also analyzed using ELISA. Pathological changes were also observed with the aid of hematoxylin-eosin (HE) staining. Our results indicated that LCA significantly reduced the levels of MPO, MDA and increased SOD and GSH activities. Furthermore, LCA also significantly inhibited the levels of TNF-α, IL-6, and IL-1β in the serum of ulcerated mice in a dose dependent manner. Immunohistological analysis indicated that LCA also significantly attenuated the overexpression of nuclear factor-κB in pretreated mice models. This findings suggests Lycium chinense Mill possesses gastroprotective properties against ethanol-induced gastric injury and could be a possible therapeutic intervention in the treatment and management of gastric ulcers.

The Effects of Moderate Exercise on Ethanol-Induced Gastric Injuries in Rats

Background: The role of oxygen-derived free radicals in the development of pathogenesis in acute gastric lesions induced by ethanol is well known. The beneficial effects of physical training on the antioxidant defenses of numerous tissues have been proved. Objectives: The present study was designed to evaluate the effects of exercise training on ethanol-induced gastric mucosal injuries in rats. Materials and Methods: In this experimental study, 28 Sprague-Dawley male rats were divided into 4 equal groups: sedentary control, exercise control, sedentary plus ethanol and exercise plus ethanol groups. The rats were subjected to moderate treadmill exercise protocol for 30 consecutive days (one hour per day). Thereafter, ethanol-treated groups received absolute ethanol (1 mL/rat) by gavage to induce gastric ulcer. Antioxidant status and lipid peroxidation of stomach wall were measured by evaluation of glutathione peroxidase (GPx), catalase activities (CAT) and thiobarbituric acid reactive substances (TBARS) concentration, respectively. Results: The histopathological findings of this study showed that moderate exercise training significantly inhibited the ethanol-induced gastric lesions in rats. Biochemical results also showed that administration of ethanol significantly decreased GPx activity and increased TBARS when compared to the sedentary control group (P < 0.05). In contrast, the exercise plus ethanol group showed higher GPx activity and lower TBARS concentration when compared to the ethanol-treated rats (P < 0.05). The catalase activity in ethanol-treated rats tended to be decreased when compared to control group. Conclusions: It seems that the preventive effects of exercise training may be mediated through increasing GPx activity subsequently inhibition of lipid peroxidation in stomach wall of rats.

Diosmin protects against ethanol-induced gastric injury in rats: novel anti-ulcer actions.

Alcohol consumption has been commonly associated with gastric mucosal lesions including gastric ulcer. Diosmin (DIO) is a natural citrus flavone with remarkable antioxidant and anti-inflammatory features that underlay its protection against cardiac, hepatic and renal injuries. However, its impact on gastric ulcer has not yet been elucidated. Thus, the current study aimed to investigate the potential protective effects of DIO against ethanol-induced gastric injury in rats. Pretreatment with DIO (100 mg/kg p.o.) attenuated the severity of ethanol gastric mucosal damage as evidenced by lowering of ulcer index (UI) scores, area of gastric lesions, histopathologic aberrations and leukocyte invasion. These actions were analogous to those exerted by the reference antiulcer sucralfate. DIO suppressed gastric inflammation by curbing of myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) levels along with nuclear factor kappa B (NF-κB) p65 expression. It also augmented the anti-inflammatory interleukin-10 (IL-10) levels. Meanwhile, DIO halted gastric oxidative stress via inhibition of lipid peroxides with concomitant enhancement of glutathione (GSH), glutathione peroxidase (GPx) and the total antioxidant capacity (TAC). With respect to gastric mucosal apoptosis, DIO suppressed caspase-3 activity and cytochrome C (Cyt C) with enhancement of the anti-apoptotic B cell lymphoma-2 (Bcl-2) in favor of cell survival. These favorable actions were associated with upregulation of the gastric cytoprotective prostaglandin E2 (PGE2) and nitric oxide (NO). Together, these findings accentuate the gastroprotective actions of DIO in ethanol gastric injury which were mediated via concerted multi-pronged actions, including suppression of gastric inflammation, oxidative stress and apoptosis besides boosting of the antioxidant and the cytoprotective defenses.

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.

Curcuma aromaticaWater Extract Attenuates Ethanol-Induced Gastritis via Enhancement of Antioxidant Status

Curcuma aromatica is an herbal medicine and traditionally used for the treatment of various diseases in Asia. We investigated the effects of C. aromatica water extract (CAW) in the stomach of rats with ethanol-induced gastritis. Gastritis was induced in rats by intragastric administration of 5 mL/kg body weight of absolute ethanol. The CAW groups were given 250 or 500 mg of extract/kg 2 h before administration of ethanol, respectively. To determine the antioxidant effects of CAW, we determined the level of lipid peroxidation, the level of reduced glutathione (GSH), the activities of catalase, degree of inflammation, and mucus production in the stomach. CAW reduced ethanol-induced inflammation and loss of epithelial cells and increased the mucus production in the stomach. CAW reduced the increase in lipid peroxidation associated with ethanol-induced gastritis (250 and 500 mg/kg, p < 0.01, resp.) and increased mucosal GSH content (500 mg/kg, p < 0.01) and the activity of catalase (250 and 500 mg/kg, p < 0.01, resp.). CAW increased the production of prostaglandin E2. These findings suggest that CAW protects against ethanol-induced gastric mucosa injury by increasing antioxidant status. We suggest that CAW could be developed for the treatment of gastritis induced by alcohol.

만성적인 에탄올 섭취로 인한 쥐의 위 조직 손상에서 방사무늬 김(Pyropia yezoensis)의 보호효과

We examined the protective effects of Pyropia yezoensis glycoprotein (PYGP) against ethanol-induced gastric damage. The experimental animals were divided into four groups. They were treated with distilled water (control), ethanol alone (EtOH), ethanol + PYGP 150 mg/kg BW (EtOH+150), or ethanol + PYGP 300 mg/kg BW (EtOH+300). The groups were treated for 4 weeks. We measured mitogen-activated protein kinase (MAPK), the apoptotic signaling pathway, and PARP activity in gastric tissues obtained from the rats. Ethanol consumption increased apoptotic signal activity and ERK, JNK, and p38 phosphorylation. PYGP reduced the apoptotic signaling pathway activity and ERK, JNK, and p38 phosphorylation. Furthermore, PYGP regulated Bcl-2 family expression. In light of these findings, PYGP appears to prevent ethanol-induced gastric injury and oxidative stress.

Gastroprotective effect of the traditional herbal medicine, Sipjeondaebo-tang water extract, against ethanol-induced gastric mucosal injury.

BackgroundSipjeondaebo-tang, a traditional herbal medicine, has been reported to activate the immune response. Although, most research has focused on its anticancer activity. The purpose of this study was to determine whether Sipjeondaebo-tang exerts antioxidant activity against ethanol-induced gastric injury.MethodsGastric mucosal injury was induced by the oral administration of absolute ethanol at 5 mL/kg to rats after 18 h fast. Sipjeondaebo-tang water extract (SDTW; 200 mg/kg of body weight) was administered to rats 2 h before the oral administration of absolute ethanol. Gastric mucosal injury was evaluated by measuring the gastric injury, such as extent of lesions, malondialdehyde (MDA) concentration, glutathione (GSH) content and activities of antioxidant enzymes including catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase, and superoxide dismutase in stomach tissue.ResultsOral administration of SDTW markedly decreased the damage by conditioning the gastric mucosa such as hemorrhage, hyperemia. Pretreatment with SDTW significantly reduced MDA concentration and significantly increased GSH content and the activities of antioxidant enzymes. In an acute toxicity study, no adverse effects of SDTW were observed at doses up to 5000 mg/kg/day.ConclusionsSDTW may protect the gastric mucosa against ethanol-induced gastric mucosa injury. These results suggested that SDTW might also play an important role in the gastroprotection based on their antioxidant effect.

Gastroprotective activity of Annona muricata leaves against ethanol-induced gastric injury in rats via Hsp70/Bax involvement.

The popular fruit tree of Annona muricata L. (Annonaceae), known as soursop and graviola, is a widely distributed plant in Central and South America and tropical countries. Leaves of A. muricata have been reported to possess antioxidant and anti-inflammatory activities. In this study, the gastroprotective effects of ethyl acetate extract of A. muricata leaves (EEAM) were investigated against ethanol-induced gastric injury models in rats. The acute toxicity test of EEAM in rats, carried out in two doses of 1 g/kg and 2 g/kg, showed the safety of this plant, even at the highest dose of 2 g/kg. The antiulcer study in rats (five groups, n=6) was performed with two doses of EEAM (200 mg/kg and 400 mg/kg) and with omeprazole (20 mg/kg), as a standard antiulcer drug. Gross and histological features showed the antiulcerogenic characterizations of EEAM. There was significant suppression on the ulcer lesion index of rats pretreated with EEAM, which was comparable to the omeprazole effect in the omeprazole control group. Oral administration of EEAM to rats caused a significant increase in the level of nitric oxide and antioxidant activities, including catalase, glutathione, and superoxide dismutase associated with attenuation in gastric acidity, and compensatory effect on the loss of gastric wall mucus. In addition, pretreatment of rats with EEAM caused significant reduction in the level of malondialdehyde, as a marker for oxidative stress, associated with an increase in prostaglandin E2 activity. Immunohistochemical staining also demonstrated that EEAM induced the downregulation of Bax and upregulation of Hsp70 proteins after pretreatment. Collectively, the present results suggest that EEAM has a promising antiulcer potential, which could be attributed to its suppressive effect against oxidative damage and preservative effect toward gastric wall mucus.

Oral administration of betaine ameliorates ethanol-induced gastric injury in rats through its antioxidant effects

The aim of this study was to evaluate whether betaine ameliorates ethanol-induced gastric injury in rats. The morphological, histological and biochemical characteristics of gastric hemorrhagic lesions in ethanol-injured rats (n = 5/group) pretreated with betaine were analyzed and compared to non-treated controls. We compared the hemorrhagic dimensions using the Image J software, lipid peroxidation by malondialdehyde (MDA) concentration and inducible nitric oxide synthase (iNOS) immunoreactivity in the gastric mucosa among treatment groups. Oral administration of 250 mg/kg betaine significantly reduced gastric hemorrhage dimensions compared with the vehicle-treated control (p <0.05). Immunohistochemical analysis showed that the expression of iNOS and its byproduct nitrotyrosine were significantly reduced in betaine-pretreated rats compared to vehicle-treated rats with ethanol injury (p < 0.05). Lipid peroxidation was also significantly reduced in the ethanol-injured rats pretreated with betaine compared with the vehicle-treated ethanol-injured group (p <0.05). Collectively, these results suggest that pretreatment of betaine ameliorates ethanol-induced gastric mucosal injury, possibly through the inhibition of oxidative stress.

Ethanol-Induced Gastric Injury: Microscopic Analysis of the Protective Effect of Frutalin

Obtained from breadfruit seeds (Artocarpus incisa), frutalin (FTL) has a range of important pharmacological properties. FTL activates and modulates lymphocytes and neutrophils and possesses gastroprotective effects. The purpose of this study was to evaluate the ability of FTL to protect the gastric mucosa of mice submitted to ethanol-induced gastric injury. The gastroprotective effect of frutalina was evaluated using a murine model of ethanol-induced gastric injury. Damage of the gastric mucosa was assessed morphologically by light, scanning electron and atomic force microscopy. Lymphocyte infiltration, necrosis, disruption of the mucosal structures and epithelial desquamation were observed in the control group. In the group pretreated with frutalina at 0.5 mg/kg, gastroprotection, reduced tissue damage and preserved submucosal and mucosal structures were observed. In conclusion, FTL displayed gastroprotective activity against ethanol-induced gastric injury, preventing the formation of gastric ulcer and reducing epithelial desquamation, glandular damage, mucosal necrosis and infiltration. The observed effects appear to be due to mechanisms previously described for frutalin.

Aqueous extract of purple Bordeaux radish, Raphanus sativus L. ameliorates ethanol-induced gastric injury in rats

The aim of this study was to evaluate whether the crude aqueous extract of purple Bordeaux radish (Raphanus sativus L.) (PBR) ameliorates ethanol-induced gastric injury in rats. Animals were divided into the following nine groups: normal, distilled water-treated vehicle control, groups orally administered PBR extract (250, 500 and 1,000 mg/kg, daily for 2 weeks), with or without ethanol treatment (5 ml/kg) 24 h after final administration of PBR extract, and a group treated with ethanol alone. Rats treated with PBR extract (250–1,000 mg/kg) for 2 weeks showed no significant effects on body weight and gastric mucosa. Pretreatment with PBR extract at doses of 500 and 1,000 mg/kg, but not 250 mg/kg, significantly ameliorated ethanol-induced gastric hemorrhages in rats (p < 0.05). The immunoreactivities of inducible nitric oxide (iNOS) and its byproduct nitrotyrosine in the gastric mucosa of ethanol-treated rats pretreated with 500 mg/kg PBR extract were significantly reduced, as compared with rats treated with ethanol alone (p < 0.05). Collectively, these findings suggest that pretreatment with PBR extract ameliorates ethanol-induced damage in the gastric mucosa, which is mediated partly by the anti-oxidative activity of the extract. The precise mechanism of this gastroprotective action of PBR extract should be investigated further.

Banhabaekchulchunma-tang, a traditional herbal formula attenuates absolute ethanol-induced gastric injury by enhancing the antioxidant status

BackgroundBanhabaekchulchunma-tang (hange-byakujutsu-tenma-to in Japanese and banxia-baizhu-tianma-tang in Chinese) is a mixture of fourteen herbs. It is used traditionally for the treatment of anemia, anorexia, general weakness, and female infertility in China, Japan, and Korea. In this study, we investigated the protective effects of a Banhabaekchulchunma-tang water extract (BCT) against ethanol-induced acute gastric injury in rats.MethodsGastric injury was induced by intragastric administration of 5 mL/kg body weight of absolute ethanol to each rat. The positive control group and the BCT group were given oral doses of omeprazole (50 mg/kg) or BCT (400 mg/kg), respectively, 2 h prior to the administration of absolute ethanol. The stomach of each animal was excised and examined for gastric mucosal lesions. To confirm the protective effects of BCT, we evaluated the degree of lipid peroxidation, the level of reduced glutathione (GSH), and the activities of the antioxidant enzymes catalase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase in the stomach. In addition, we conducted an acute toxicity study to evaluate the safety of BCT according to OECD guideline.ResultsBCT reduced ethanol-induced hemorrhage, hyperemia, and loss of epithelial cell in the gastric mucosa. BCT reduced the increased lipid peroxidation associated with ethanol-induced acute gastric lesions, and increased the mucosal GSH content and the activities of antioxidant enzymes. In addition, BCT did not cause any adverse effects at up to 5000 mg/kg.ConclusionsThese results indicate that BCT protects the gastric mucosa against ethanol-induced gastric injury by increasing the antioxidant status. We suggest that BCT could be developed as an effective drug for the treatment of gastric injury caused by alcohol intake.

Gastroprotective Effect of Hintonia latiflora and Hintonia standleyana Aqueous Extracts and Compounds

Abstract Ethnopharmacological relevance The stem-barks of Hintonia latiflora and Hintonia standleyana , locally known as “copalchi”, are used for treating several maladies such as diabetes and gastrointestinal complaints, including gastric ulcers. Although the antidiabetic properties have been demonstrated, the gastroprotective action remains unexplored. Aim of the study The main goals of this study were to establish the potential acute toxicity and the gastroprotective activity of aqueous extracts and compounds from Hintonia latiflora and Hintonia standleyana in order to demonstrate their preclinical efficacy for the treatment of gastric ulcers in Mexican folk medicine. Materials and methods The aqueous extracts from the stem-barks (HLSB and HSSB) and leaves (HLL and HSL) from Hintonia latiflora and Hintonia standleyana were prepared by infusion. Investigation of the acute toxicity was accomplished by the Lorke method. The gastroprotective effect was assessed by means of a conventional ethanol-induced gastric injury model in rats using carbenoxolone as positive control. 5- O -[β- d -apiofuranosyl-(1→6)-β- d -glucopyranosyl]-7-methoxy-3′,4′-dihydroxy-4-phenylcoumarin ( 1 ) and chlorogenic acid ( 2 ) were also assayed. Preliminary mechanism of action of the tested compounds was analyzed using the same pharmacological models but pretreating the animals with N G - nitro- l -arginine methyl ester ( l -NAME), N -ethylmaleimide (NEM) and indomethacin. Results Investigation of the acute toxicity revealed that infusions of the leaves and stem-barks of both Hintonia species were not toxic to mice (LD 50 >5000 mg/kg in all cases). HLSB, HSSB, HLL and HSL provoked a significant gastroprotective effect [80.5±3.35% (ED 50 =184.7 mg/kg), 80.26±3.96%, 75.1±7.26% (ED 50 =109.1 mg/kg), 76.85±3.17% (ED 50 =149.7 mg/kg) of gastroprotection respectively]. Compounds 1 and 2 , present in all the extracts, were also active [68.85±8.4% (ED 50 =15 mg/kg), 74.04±4.4% (ED 50 =26 mg/kg) of gastroprotection respectively] and their mode of action involved non-protein sulfhydryl endogenous (NP-SH) compounds, since only pretreatment with NEM inhibited their gastroprotective action. Conclusions The present investigation tends to support the ethnomedical use of HLSB, HSSB for treating gastric ulceration. Since HLL and HSL were also active, the leaves could be use alternatively, which in terms of natural resources conservation is an outstanding finding, considering that the plant populations of both Hintonia are scarce and in danger of extinction. Mainly two compounds ( 1 and 2 ) are important active principles of the plants.

An imbalance between VEGF and endostatin underlies impaired angiogenesis in gastric mucosa of aging rats

Gastric mucosa of aging individuals exhibits increased susceptibility to injury and delayed healing. Our previous studies in young rats showed that healing of mucosal injury depends on and is critically dependent on VEGF and angiogenesis. Since angiogenesis in aging gastric mucosa has not been examined before, in this study we examined the extent to which angiogenesis is impaired in gastric mucosa of aging vs. young rats and determined the underlying mechanisms with a focus on mucosal expression of VEGF (proangiogenic factor) and endostatin (antiangiogenic factor). Aging rats had significantly impaired gastric angiogenesis by ~12-fold, 5-fold, 4-fold, and 3-fold, respectively (vs. young rats; all P < 0.001) at 24, 48, 72, and 120 h following ethanol-induced gastric injury and reduced and delayed healing of mucosal erosions. In gastric mucosa of aging (vs. young) rats at baseline, VEGF expression was significantly reduced, whereas endostatin levels were significantly increased (P < 0.05 and P < 0.01, respectively). In contrast to young rats, gastric mucosal VEGF levels did not increase following ethanol-induced injury in aging rats. MMP-9 enzyme activity was significantly higher in gastric mucosa of aging vs. young rats both at baseline (2.7-fold) and 24 h (3.8-fold) after ethanol injury (both P < 0.001). Since endostatin is generated from collagen XVIII by MMP-9, this finding can explain the mechanism of increased endostatin expression in aging gastric mucosa. The above findings demonstrate that reduced VEGF and increased endostatin result in the impaired angiogenesis and delayed injury healing in gastric mucosa of aging rats.

In vivo antioxidant and antiulcer activity of Parkia speciosa ethanolic leaf extract against ethanol-induced gastric ulcer in rats.

BackgroundThe current study was carried out to examine the gastroprotective effects of Parkia speciosa against ethanol-induced gastric mucosa injury in rats.Methodology/Principal FindingsSprague Dawley rats were separated into 7 groups. Groups 1–2 were orally challenged with carboxymethylcellulose (CMC); group 3 received 20 mg/kg omeprazole and groups 4–7 received 50, 100, 200 and 400 mg/kg of ethanolic leaf extract, respectively. After 1 h, CMC or absolute ethanol was given orally to groups 2–7. The rats were sacrificed after 1 h. Then, the injuries to the gastric mucosa were estimated through assessment of the gastric wall mucus, the gross appearance of ulcer areas, histology, immunohistochemistry and enzymatic assays. Group 2 exhibited significant mucosal injuries, with reduced gastric wall mucus and severe damage to the gastric mucosa, whereas reductions in mucosal injury were observed for groups 4–7. Groups 3–7 demonstrated a reversal in the decrease in Periodic acid-Schiff (PAS) staining induced by ethanol. No symptoms of toxicity or death were observed during the acute toxicity tests.ConclusionTreatment with the extract led to the upregulation of heat-shock protein 70 (HSP70) and the downregulation of the pro-apoptotic protein BAX. Significant increases in the levels of the antioxidant defense enzymes glutathione (GSH) and superoxide dismutase (SOD) in the gastric mucosal homogenate were observed, whereas that of a lipid peroxidation marker (MDA) was significantly decreased. Significance was defined as p<0.05 compared to the ulcer control group (Group 2).

Acute toxicity and gastroprotection studies with a newly synthesized steroid.

BackgroundSynthetic steroids, such as 9α-bromobeclomethasonedipropionate, have shown gastroprotective activity. For example, the potent glucocorticoid steroid, beclomethasone dipropionate, has been used for treatment of bowel ulcerations. The purpose of the present study was to evaluate the effect of a synthetic steroid, (20S)-22-acetoxymethyl-6β-methoxy-3α,5-dihydro-3′H-cyclopropa[3α,5]-5α-pregnane (AMDCP), on ethanol-induced gastric mucosa injuries in rats.Methodology/Principal FindingRats were divided into 8 groups. The negative control and ethanol control groups were administered Tween 20 (10%v/v) orally. The reference control group, 20 mg/kg omeprazole (10% Tween 20, 5 mL/kg), was administrated orally. The experimental groups received 1, 5, 10, 15 or 20 mg/kg of the AMDCP compound (10% Tween 20, 5 mL/kg). After 60 min, Tween 20 and absolute ethanol was given orally (5 mL/kg) to the negative control group and to the rest of the groups, and the rats were sacrificed an hour later. The acidity of gastric content, gastric wall mucus and areas of mucosal lesions were assessed. In addition, histology and immunohistochemistry of the gastric wall were assessed. Prostaglandin E2 (PGE2) and malondialdehyde (MDA) content were also measured. The ethanol control group exhibited severe mucosal lesion compared with the experimental groups with fewer mucosal lesions along with a reduction of edema and leukocyte infiltration. Immunohistochemical staining of Hsp70 and Bax proteins showed over-expression and under-expression, respectively, in the experimental groups. The experimental groups also exhibited high levels of PGE2 as well as a reduced amount of MDA. AMDCP decreased the acidity and lipid peroxidation and increased the levels of antioxidant enzymes.Conclusion/SignificanceThe current investigation evaluated the gastroprotective effects of AMDCP on ethanol-induced gastric mucosal lesions in rats. This study also suggests that AMDCP might be useful as a gastroprotective agent.

Role of the NO/KATP pathway in the protective effect of a sulfated-polysaccharide fraction from the algae Hypnea musciformis against ethanol-induced gastric damage in mice

Seaweeds are the most abundant source of polysaccharides such as alginates and agar, as well as carrageenans. This study aimed to investigate the gastroprotective activity and the mechanism underlying this activity of a sulfated-polysaccharide fraction extracted from the algae Hypnea musciformis (Wulfen) J.V. Lamour. (Gigartinales– Rhodophyta). Mice were treated with sulfated-polysaccharide fraction (3, 10, 30, and 90mg/kg, p.o.) and, after 30min, they were administered 50% ethanol (0.5mL/25g, p.o.). After 1h, gastric damage was measured using a planimeter. In addition, samples of the stomach tissue were obtained for histopathological examination and for assays to determine the glutathione and malondialdehyde levels. Other groups of mice were pretreated with NG-nitro-L-arginine methyl ester (L-NAME, 10mg/kg, i.p.), aminoguanidine (100mg/kg, i.p.), or glibenclamide (10mg/kg, i.p.). After 30min to the aminoguanidine group and 1h to the other groups, sulfated-polysaccharide fraction (30mg/kg, p.o.) was administered and gastric damage was induced as described above. Sulfated-polysaccharide fraction prevented ethanol-induced gastric injury in a dosedependent manner. However, treatment with L-NAME or glibenclamide reversed this gastroprotective effect. Administration of aminoguanidine did not infl uence the effect of sulfated-polysaccharide fraction. Our results suggest that sulfated-polysaccharide fraction exerts a protective effect against ethanol-induced gastric damage via activation of the NO/KATP pathway.

Gastroprotective effects of Leejung-tang, an oriental traditional herbal formula, on ethanol-induced acute gastric injury in rats

Leejung-tang (LJT, Rechu-to in Japanese and Lizhong-tang in Chinese) is an oriental traditional traditional herbal formula. LJT has been used for treatment of gastrointestinal disorders in Korea, Japan, and China for a long time. In present study, we investigated the protective effects of LJT against absolute ethanol induced gastric injuries. Rats in the control group were given PBS orally (5 mL/kg body weight) as the vehicle, and the absolute-ethanol group (EtOH group) received absolute ethanol (5 mL/kg body weight) by oral gavage. Rats in the positive control group were given omeprazole orally (50 mg/kg body weight) 2 h prior to the administration of absolute ethanol. The treatment groups received LJT (400 mg/kg body weight) 2 h prior to absolute ethanol administration. All rats were sacrificed 1 h after receiving the ethanol treatment. The stomach was excised for macroscopic examination and biochemical analysis. The administration of LJT protected gastric mucosa against ethanol-induced acute gastric injury, including hemorrhage and hyperemia. LJT reduced the increase in lipid peroxidation in ethanol-induced acute gastric lesions. LJT increased GSH content and activities of the antioxidant enzymes, catalase, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, and superoxide dismutase. These results indicate that LJT protects gastric mucosa against ethanol-induced acute gastric injury by increasing their antioxidant content. We suggest that LJT can be developed as an effective drug for the treatment of acute gastric injury.

Musashi-1 post-transcriptionally enhances phosphotyrosine-binding domain-containing m-Numb protein expression in regenerating gastric mucosa.

ObjectiveUpregulation of the RNA-binding protein Musashi-1 (Msi1) has been shown to occur in rat gastric corpus mucosa after ethanol-induced mucosal injury. However, there is no direct evidence linking Msi1 with gastric regeneration. We examined the process of tissue repair after acute gastric mucosal injury with Msi1-knock-out (KO) mice to clarify the role of Msi1 and Msi1-dependent regulation of m-Numb expression in regenerating gastric mucosa.MethodsAcute gastric injury was induced in Msi1-KO and wild-type ICR mice by administering absolute ethanol. Expression of the splicing variants of m-Numb mRNA and protein in the gastric mucosa were analyzed by quantitative RT-PCR and western blotting, respectively.ResultsWe demonstrated that phosphotyrosine-binding domain-containing m-Numb expression was significantly upregulated at both the mRNA and protein levels in wild-type mice at 3 h after ethanol-induced acute gastric injury. In contrast, in Msi1-KO mice, the m-Numb protein was expressed weakly, and was associated with delayed regeneration of the injured gastric mucosal epithelium. In the Msi1-KO mouse, the ratio of m-Numb mRNA to total m-Numb mRNA in the heavy polysome fractions was lower than that in the wild-type mouse. Further, we showed that m-Numb-enhancement in gastric mucous cells induced the expression of prostate stem cell antigen and metallothionein-2. Under the m-Numb enhancing condition, the gastric cells exhibited enhanced cell proliferation and were significantly more resistant to H2O2-induced cell death than control cells.ConclusionsMsi1-dependent post-transcriptional enhancement of m-Numb is crucial in gastric epithelial regeneration.