Ethanol-induced Gastric Injury In Rats Research Articles

Fish oil ameliorates ethanol-induced gastric injury in rat by modulating gene related to apoptosis

Gastric ulcers are a type of digestive disease that can severely affect a person's quality of life. Our study aimed to investigate the effects of fish oil on ethanol-induced gastric ulcers in rats, with the purpose of providing more comprehensive information on the topic. The study looked at various factors such as gastric ulcer index, and nitric oxide (NO) levels in stomach tissue. To investigate apoptosis, the mRNA levels of Bax, Bcl-2, and Caspase 3 were analyzed. The results showed that fish oil can reduce gastric acidity and the gastric ulcer index in cases of ethanol-induced gastric ulcers. It was found that fish oil can increase NO levels and improve the anti-apoptotic system by increasing the expression of Bcl-2 while decreasing the expression of Bax and Caspase 3. In general, the study demonstrates that fish oil can protect the stomach from ethanol-induced damage by reducing the apoptosis pathway via nitric oxide.

Gastroprotective potential of red onion (Allium cepa L.) peel in ethanol-induced gastric injury in rats: Involvement of Nrf2/HO-1 and HMGB-1/NF-κB trajectories

Ethnopharmacological relevanceThe utilization of plants with therapeutic properties in traditional medicine has a longstanding practice. Among them, the well-known Allium cepa L. commonly known as onion has been valued for its anti-inflammatory and antioxidant potential in the treatment of various ailments, including gastric ulcers. Aim of the studyThis study investigated the gastroprotective potential of red onion peel extract and its fractions in a rat model of ethanol-induced gastric ulcer. Moreover, their phytochemical profiles were compared to identify the active metabolites. Materials and methodsMass spectrometry-based metabolomics and chemometrics were performed for phytochemical analysis. Ethanol-induced gastric ulcer model was used to assess the gastroprotective activity. Nine groups of rats were allocated as follows: Group 1 was the normal control; Group 2 rats were used as a positive control/model and received 1 mL of absolute ethanol; and Group 3 rats were treated with famotidine at a dose of 20 mg/kg orally. Group 4 and 5 rats were treated with total acidified ethanolic extract (T1, T2). Group 6 and 7 rats were treated with anthocyanins-rich fractions (P1, P2). Groups 8 and 9 were the flavonoids-rich fraction (S1, S2) treatment. Prior to scarification, the ulcer index in mm was obtained from gastric tissues photographed beside a ruler with further analysis using ImageJ software. ResultsSeventy key major and discriminatory metabolites were identified including flavonoids, anthocyanins, phenolic acids, and miscellaneous compounds. The examined extract and its fractions significantly reduced the ulcer index and inflammatory cytokines via downregulating HMGB-1/NF-κB. Also, they augmented the expression of Nrf2/HO-1 and reduced NOX1/4 mRNA expression. Moreover, there was a significant reduction in the oxidative stress and apoptotic biomarkers as well as a noticeable enhancement in histopathological changes of the stomach tissues. ConclusionRed onion peels have a promising dose dependent gastroprotective potential in alcohol-induced ulcers via modulating Nrf2/HO-1 and HMGB-1/NF-κB trajectories. This highlights the potential of red onion peels in treating gastric ulcers.

Low dose administration of mature silkworm powder induces gastric mucosal defense factors in ethanol-induced gastric injury rat model.

Gastric mucosa is important to protect the gastric damage against external factors. We previously reported the gastro-protective effects of steamed and freeze-dried mature silkworm larval powder (SMSP) in ethanol-treated rats. However, the factors that promote mucosal formation still remain unclarified. In this study, we evaluated the effect of SMSP on the restoration and maintenance of gastric mucosal layer as well as anti-inflammatory response in ethanol-induced stomach injury in rats. A significant decrease of ulcer indexes, histopathological scores and pro-inflammatory cytokine levels was observed in SMSP-treated group. In addition, SMSP protected the mucosal layer from ethanol-induced gastric damage by increasing the expression of nitric oxide synthases and heat shock proteins, along with promoting genes related gastric mucosal protection and biosynthesis including mucin 5AC and trefoil factors. These results demonstrate that SMSP attenuates the pro-inflammatory responses and strengthens the gastric mucosal layer, thus exhibiting gastro-protective effect against ethanol-induced gastric injury in rats.

Gastro-protective actions of Aloe barbadensis Miller mitigate ethanol-induced gastric injury in rats

Purpose: To investigate the gastroprotective effect of leaf extract of Aloe barbadensis on ethanolinduced gastric ulcer in rats.Methods: Healthy male Wistar rats (n = 30) weighing 180 - 220 g (mean weight = 200 ± 20 g) were randomly assigned to 6 groups (5 rats/group): control group, gastric ulcer group, two Aloe barbadensis extract groups (250 and 500 mg/kg), cimetidine group and indomethacin group. Gastric ulcer was induced via oral injection of absolute ethanol at a dose of 1 mL/kg after a 24-h fast. Gross evaluation, determination of gastric juice acidity and histological examination of gastric tissue were carried out.Results: Treatment of gastric ulcer rats with Aloe barbadensis extract significantly reduced ulcerated area (UA), ulcer index (UI), and acidity of gastric juice (p < 0.05). Injection of 1 % carrageenan into rat hind paw led to a time-dependent increase in paw volume which peaked 3 h after injection. However, the Aloe barbadensis extract significantly and dose-dependently reduced the volume of inflamed paw, and inhibited edema formation (p < 0.05). It also markedly reduced or completely eliminated edema and leucocyte infiltration. Moreover, treatment of gastric ulcer rats with Aloe barbadensis leaf extract led to significant and dose-dependent reduction in gastric tissue MDA level (p < 0.05). Histological examination of the gastric wall showed that control rats had severe injury in gastric mucosa,accompanied by edema and leucocytes infiltration, relative to rats pretreated with extract which showed marked gastric protection and inhibition of edema and leucocytes infiltration. Moreover, the extract treatment protected the gastric surface against ulceration as indicated by reduced lesions in the treated rat model.Conclusion: These results show that Aloe barbadensis mitigates ethanol-induced gastric injury in rats via inhibition of lipid peroxidation and inflammation. Thus, the extract has potentials for development into a therapeutic agent for the management of gastric ulcer.
 Keywords: Aloe barbadensis, Gastric ulcer, Gastric mucosa, Inflammation, Lipid peroxidation

Glutaraldehyde-crosslinked chitosan-polyethylene oxide nanofibers as a potential gastroretentive delivery system of nizatidine for augmented gastroprotective activity

Nizatidine (NIZ), a histamine H2-receptor antagonist, is soluble and stable in the stomach, however, it exhibits a short half-life and a rapid clearance. Therefore, chitosan (CS) and polyethylene oxide (PEO) nanofibers (NFs) at different weight ratios were prepared by electrospinning and characterized. The selected uncrosslinked and glutaraldehyde-crosslinked NFs were investigated regarding floating, solid-state characteristics, in vitro release, and in vitro cytotoxicity. The cytoprotective activity against ethanol-induced gastric injury in rats was evaluated through macroscopical, histopathological, immunohistochemical, and oxidative stress examinations. NFs based on 8:2 CS:PEO exhibited the smallest diameter (119.17 ± 22.05 nm) and the greatest mucoadhesion (22.82 ± 3.21 g/cm2), so they were crosslinked with glutaraldehyde. Solid-state characterization indicated polymers interaction, a successful crosslinking, and NIZ dispersion in NFs. Crosslinking maintained swollen mats at pH 1.2 (swelling% = 29.47 ± 3.50% at 24 h), retarded their erosion at pH 6.8 (swelling%= 84.64 ± 4.91% vs. 25.40 ± 0.79% for the uncrosslinked NFs at 24 h), augmented the floating up to 24 h vs. 10 min for the uncrosslinked NFs at pH 1.2 and prolonged the drug release (%drug released ≥ 93% at 24 h vs. 4 and 5 h for the uncrosslinked NFs at pHs 1.2 and 6.8, respectively). The viability of Caco-2 cells ≥ 86.87 ± 6.86% revealed NFs biocompatibility and unreacted glutaraldehyde removal. Crosslinking of 8:2 CS:PEO NFs potentiated the antiulcer activity (38.98 vs. 8.67 for the uncrosslinked NFs) as well as it preserved the gastric wall architecture, COX-2 expression, and oxidative stress markers levels of the normal rats.

Tangeretin Protects against Ethanol‐Induced Injury in Gastric Mucosa of Rats via its Antioxidants and Anti‐inflammatory Activity

Tangeretin (TG), a polymethoxy citrus flavone, has attracted attention due to its significant antioxidant and anti‐inflammatory activities. It showed valuable pharmacological actions and protected against cancer, diabetic‐, liver‐ and renal‐induced injuries. However, its antiulcer activity has not been investigated.This study aimed to explore the possible protective effects of TG against ethanol‐induced gastric injury in rats. Adult male Wistar rats were used and divided into five groups: Control, TG, EtOH, EtOH+TG and EtOH+ Pantoprazole (PAN). Gastric injury was induced by a single dose of Absolute ethanol (5ml/Kg, p.0).Alcohol administration leads to significant macroscopic, histologic and biochemical gastric injuries. Treatment with TG (100mg/kg p.o.) protected against EtOH‐induced gastric injuries as demonstrated by the decrease in the ulcer and bleeding scores. Tangeretin boosted the antioxidants properties of the gastric mucosa via the inhibition of Malondialdehydes (MDA) and nitric oxides (NO) while improving glutathione (GSH), superoxide dismutase (SOD) and the nuclear factor erythroid 2–related factor 2 (Nrf2). Tangeretin curbed gastric inflammation by decreasing myeloperoxidase (MPO) and tumor necrosis factor‐α (TNF‐α) while increasing the anti‐inflammatory interleukin‐10 (IL‐10). In addition, TG caused the upregulation of the gastric cytoprotective prostaglandin E2 (PGE2). These results were comparable to those produced by PAN; the proton pump inhibitor.These findings reported for the first time the gastroprotective actions of TG in EtOH‐induced gastric injury which were mediated via suppression of inflammation and oxidative stress in addition to enhancing the antioxidant and the cytoprotective defenses.Support or Funding InformationThis work has been financially supported by the research grant# 2017‐A‐PH‐03 from the Deanship of Graduate Studies and Research, Ajman University.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Pretreatment with Lactobacillus reuteri F-9-35 attenuates ethanol-induced gastric injury in rats.

BackgroundPrevious studies suggested that probiotics intervention may be one of the methods for preventing and/or treating gastric ulcer.ObjectiveThe aim of the study was to compare the preventive effects of a spaceflight mutant Lactobacillus reuteri F-9-35 and its wild type on ethanol-induced gastric injury in rats.DesignForty rats were randomly allocated into five groups: a normal group (NOR), ethanol group (EtOH), skim milk group (MILK), L. reuteri F-9-35 group (F935) and wild-type group (WT). The NOR and EtOH groups received 1 ml of distilled water by daily gavage for 14 days. The MILK group received 1 ml of skim milk alone, while the F935 and WT groups were administered 1 ml of skim milk containing the mutant and wild type (1 × 1010 colony-forming unit/ml) by daily gavage for 14 days, respectively. Acute gastric injury was induced by absolute alcohol 1 h after the final administration of different treatments, except for the NOR group.ResultsPretreatment with L. reuteri F-9-35, but not milk alone or milk with the L. reuteri wild type, showed significant reduction of ethanol-induced gastric injury, as evidenced by lowering of ulcer index, ulcer area (%), and histological lesion. F-9-35 decreased the levels of lipid peroxidation and myeloperoxidase and increased mucus, glutathione, and nitric oxide levels in gastric tissue. Moreover, F-9-35 inhibited the expression of proinflammatory genes including gastric tumor necrosis factor-α, interleukin-1β, and cyclooxygenase-2 and decreased the activity of nuclear factor kappa B (NF-κB).ConclusionThese findings indicated that L. reuteri F-9-35 pretreatment can attenuate ethanol-induced gastric injury in rats by inhibiting oxidative stress and inflammatory response. Together, L. reuteri F-9-35 has potential preventive efficacy on gastric ulcer.

Momordica charantia polysaccharides ameliorate oxidative stress, inflammation, and apoptosis in ethanol-induced gastritis in mucosa through NF-kB signaling pathway inhibition

This study investigated the therapeutic role of polysaccharides from M. charantia and their mechanism of action against ethanol-induced gastric ulcers in rats. Their effects were determined through macroscopic evaluation of the gastric cavity (gastric ulcer index [GUI]), changes in PGE2, lipid peroxidation (malondialdehyde), antioxidant systems (catalase and reduced glutathione), inflammatory markers (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and myeloperoxidase [MPO]), apoptotic markers (caspase 3, Bax, and Bcl-2), nuclear factor-κB (NF-κB [p65]), and histopathological staining (H&E and PAS). Pretreatment with MCP (300mg/kg p.o.) attenuated the severity of ethanol-induced gastric mucosal damage, reductions in GUI, histopathologic aberrations, and neutrophil invasion, and PGE2 upregulation. These actions were similar to those of omeprazole, a reference anti-ulcer drug. MCP repressed gastric inflammation through the reduction of MPO, TNF-α, and IL-6, and prevented gastric oxidative stress through the inhibition of lipid peroxides with the concomitant enhancement of glutathione and catalase activity. Apoptotic markers indicated that MCP suppressed Bax and caspase-3 activity and enhanced the anti-apoptotic protein Bcl-2, which favored cell survival. MCP downregulated NF-κB and upregulated IκBα. Our study results suggested that the prophylactic administration of MCP reduced ethanol-induced gastric injury in rats through the suppression of gastric inflammation and oxidative stress, predominantly via NF-κB inhibition.

Allium Cepa Ameliorates Ethanol-Induced Gastric Injury in Rats Via Reduction in Gastric Neutrophils Infiltration

Neutrophil-derived oxygen free radicals have been implicated in the aetiology of gastric tissue damage. In this study, the ameliorative effects of Allium cepa on neutrophil infiltration, lipid peroxidation and antioxidant enzyme activities in the ethanol-induced gastric injury were examined. Twenty four adult male Wistar rats were used for this study and divided into four groups; Control, Allium cepa, Allium cepa + Ethanol and Ethanol. Allium cepa was administered (1mL/100g body weight) daily for twenty eight days while 0.2mL of 98% (v/v) ethanol per 23g Body Weight was used to induced gastric damage. Macroscopic measurement of ulcer area, histological examination and biochemical analyses (Malondialdehyde level, Myeloperoxidase (index of neutrophil accumulation), Superoxide dismutase (SOD) and Catalase (CAT) activities) were carried out in plasma and gastric tissue. Ethanol administration significantly (p<0.05) increased ulcer score and ulcer index, decreased percentage ulcer inhibition, increased MDA and MPO, decreased SOD and CAT activities. Histological findings show glandular destruction in the gastric mucosa and infiltration of inflammatory cells in ethanol only group. These effects were ameliorated with Allium cepa pre-treatment. The results obtained from this study demonstrate the ameliorative effect of Allium Cepa on ethanol-induced gastric injury by reduction in gastric neutrophils infiltration and increased antioxidant activities. Keywords: Gastric, Allium Cepa, Neutrophil, Myeloperoxidase

Gastroprotective effect of mature silkworm, Bombyx mori against ethanol-induced gastric mucosal injuries in rats

Gastric ulcer is a clinical condition characterized by ulceration of the surface of the gastric mucosa. Alcohol consumption has been identified as a major cause of gastric ulceration. The silkworm, Bombyx mori, produces diverse functional materials including silk proteins. Here, we evaluated whether Steamed and freeze-dried Mature Silkworm larval Powder (SMSP) can prevent ethanol-induced gastric injury in rats. Sprague-Dawley rats pretreated with SMSP (0.1 or 1 g/kg body weight) or normal diet (AIN-76A) were subjected to intragastric administration of absolute ethanol (3 g/kg body weight, 3 h). Pretreatment with SMSP significantly prevented ethanol-induced gastric mucosal ulceration and hemorrhagic injury, by which improved the total antioxidant capacity and mucus secretion and suppressed the pro-inflammatory responses through inhibiting the recruitment of immune cells. SMSP exerted protective effects in ethanol-induced gastritis via the regulation of anti-oxidative and pro-inflammatory signaling pathway, suggesting SMSP could be anticipating remedy for the treatment of ethanol-induced gastric injury.

Gastroprotective effects of chebulagic acid against ethanol-induced gastric injury in rats

Gastric ulcer is a major complication of gastrointestinal disease. This study focuses on the gastroprotection and potential mechanism of chebulagic acid (CA) in acute gastric ulceration induced by ethanol in rats. Specifically, in animal study, gastric ulceration was induced by ethanol, morphological features of gastric tissue were observed by ulcer score, H&E, masson and CD31 staining. CA can effectively decrease gastric injury, oxidative stress and proinflammatory cytokines. In addition, significant augment of prostaglandin E2 (PGE2) and nitric oxide (NO) was observed in the gastric tissues pretreated by CA. And CA prevented microcirculatory damage, aroused reparation of vascular architecture, and promoted collagen production, in associated with upregulated expressions of MMP-2, membrane type (MT) 1-MMP, VEGF, and transforming growth factor (TGF)-β. Taken together, these results indicated that CA had a considerable gastroprotective effect on ethanol-induced gastric injury. The underlying mechanism may be ascribed to the improvement of anti-oxidant and anti-inflammatory status as well as accelerating angiogenesis.

Alpha-boswellic acid protects against ethanol-induced gastric injury in rats: involvement of nuclear factor erythroid-2-related factor 2/heme oxygenase-1 pathway.

The purpose of this study was to assess the gastroprotective properties of alpha-boswellic acid (α-BA), a pentacyclic triterpene compound from extracts of Frankincense. The gastroprotection of α-BA was assessed with ethanol-induced gastric lesions model, by histopathological assessment and measuring gastric juice acidity (pH), gastric wall mucus (GWM), prostaglandins E2 (PGE-2), membrane lipids peroxidation (MDA), superoxide dismutase (SOD) activity, catalase (CAT) activity and amount of nitric oxide (NO). The gastroprotective effects of α-BA through the nuclear factor erythroid-2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) anti-oxidative pathway were presented and measured by immunohistochemistry and Western blot. The results showed that α-BA reduced injuries associated with the administration of ethanol, gastric juice acidity and the formation of MDA and increased CAT activity and SOD activity and the level of NO and PGE-2 in a dose-depended manner. The expression of both Nrf2 and HO-1 was significantly increased in the group treated with 200 mg/kg α-BA, which suggested that activation of the Nrf2/HO-1 pathway might be critical in α-BA's prevention of gastric ulcers. These findings demonstrate that α-BA decreases oxidative stress and that the Nrf2/HO-1 pathway might play a role in the gastroprotective action of α-BA in ethanol-induced gastric injury in rats.

Protective Effects of Manassantin A against Ethanol-Induced Gastric Injury in Rats.

Manassantin A, a neolignan isolated from Saururus chinensis, is a major phytochemical compound that has various biological activities, including anti-inflammatory, neuroleptic, and human acyl-CoA : cholesterol acyltransferase (ACAT) inhibitory activities. In this study, we investigated the protective effects of manassantin A against ethanol-induced acute gastric injury in rats. Gastric injury was induced by intragastric administration of 5 mL/kg body weight of absolute ethanol to each rat. The positive control group and the manassantin A group were given oral doses of omeprazole (20 mg/kg) or manassantin A (15 mg/kg), respectively, 1 h prior to the administration of absolute ethanol. Our examinations revealed that manassantin A pretreatment reduced ethanol-induced hemorrhage, hyperemia, and epithelial cell loss in the gastric mucosa. Manassantin A pretreatment also attenuated the increased lipid peroxidation associated with ethanol-induced acute gastric lesions, increased the mucosal glutathione (GSH) content, and enhanced the activities of antioxidant enzymes. The levels of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β were clearly decreased in the manassantin A-pretreated group. In addition, manassantin A pretreatment enhanced the levels of cyclooxygenase (COX)-1, COX-2, and prostaglandin E2 (PGE2) and reduced the inducible nitric oxide synthase (iNOS) overproduction and nuclear factor kappa B (NF-κB) phosphorylation. Collectively, these results indicate that manassantin A protects the gastric mucosa from ethanol-induced acute gastric injury, and suggest that these protective effects might be associated with COX/PGE2 stimulation, inhibition of iNOS production and NF-κB activation, and improvements in the antioxidant and anti-inflammatory status.

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.

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.

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.

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.

Mechanistic Studies of the Anti-Ulcerogenic Activity and Acute Toxicity Evaluation of Dichlorido-Copper(II)-4-(2-5-Bromo-benzylideneamino)ethyl) Piperazin-1-ium Phenolate Complex against Ethanol-Induced Gastric Injury in Rats

The compound dichlorido-copper(II)-4-(2-5-bromobenzylideneamino)ethyl) piperazin-1-ium phenolate (CuLBS) was synthesized, characterized and screened for acute toxicity and protective activity against ethanol-induced gastric mucosal injury in rats. Gross microscopic lesions, biochemical and immunological parameters and histochemcial staining of glycogen storage were taken into consideration. Oral administration of CuLBS (30 and 60 mg/Kg) for two weeks dose-dependently flattened gastric mucosa, significantly increased gastric mucus and total acidity, compared with control group (P < 0.01). Serum levels of liver enzymes aspartate (AST) and alanine transaminases (ALT), pro-inflammatory (IL-6 and TNF-α) and anti-inflammatory (IL-10) cytokines in the rats exposed to ethanol induced ulceration have been altered. Administration of CuLBS showed considerable (P < 0.05) protection against ulceration by modulating the acute alterations of cytokines AST, ALT and stomach glycogen. Interestingly, CuLBS did not interfere with the natural release of nitric oxide. CuLBS alone (60 mg/Kg) did not exhibit any ulcerogenic effect as assessed using Adami’s scoring scale. An acute toxicity study showed that rats treated with CuLBS (1,000 and 2,000 mg/Kg) manifested no abnormal signs. These findings therefore, suggested that the gastroprotective activity of CuLBS might contribute in modulating the inflammatory cytokine-mediated oxidative damage to gastric mucosa.