Gastric Mucosal Lesions In Rats Research Articles

Celastrus orbiculatus extract reverses precancerous lesions of gastric cancer by inhibiting autophagy via regulating the PDCD4-ATG5 signaling pathway.

Celastrus orbiculatus ethyl acetate extract (COE) is the main extract of the stem of the Chinese herbal C. orbiculatus, which has anti-tumor and anti-inflammatory biological effects. Our previous study showed that COE had a certain reversal effect on the precancerous lesions of gastric cancer (PLGC) in rats, but the exact mechanism of action remains elusive. We aimed to explore the therapeutic effects of COE on PLGC and the potential mechanisms. The PLGC rat model was successfully constructed by N-methyl-N´-nitro-N-nitrosoguanidine (MNNG) multifactorial induction method. Then, COE was prepared to treat the PLGC rat model. Hematoxylin & eosin staining was used to observe gastric mucosal lesions in rats, AB-PAS and HID-AB staining were used to observe intestinal metaplasia. PDCD4-ATG5 signaling pathway was detected by immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR) in vivo, and autophagy level was detected by IHC, transmission electron microscopy, and RT-PCR in vivo. Besides, the PLGC (MC) cell model was successfully constructed by treating GES-1 cells with MNNG. Then, the morphology, proliferation, and apoptosis of MC cells, and the role of the PDCD4-ATG5 signaling pathway and autophagy in MC cells were evaluated by COE and after the overexpression of PDCD4 treatment. COE significantly improved gastric mucosal injury and cellular heteromorphism and retarded the progression of PLGC in rats. Further studies indicated COE not only inhibited the level of autophagy but also interfered with the PDCD4-ATG5 signaling pathway in vivo. On the other hand, COE treatment could effectively reverse MC cell damage, inhibit MC cell proliferation, and promote MC cell apoptosis. Furthermore, COE also promoted PDCD4 and inhibited ATG5 expression in vitro, and the inhibitory effect of COE on ATG5-mediated autophagy was further enhanced after the overexpression of PDCD4. The study revealed that COE could regulate the PDCD4-ATG5 signaling pathway to inhibit autophagy in gastric epithelial cells, which contributes to reversing the progression of PLGC.

Retraction: Antioxidant Properties and Gastroprotective Effects of 2-(Ethylthio)Benzohydrazones on Ethanol-Induced Acute Gastric Mucosal Lesions in Rats.

Retraction: Antioxidant Properties and Gastroprotective Effects of 2-(Ethylthio)Benzohydrazones on Ethanol-Induced Acute Gastric Mucosal Lesions in Rats.

New biofunctional effects of oleanane-type triterpene saponins.

In the current review, we describe the novel biofunctional effects of oleanane-type triterpene saponins, including elatosides, momordins, senegasaponins, camelliasaponins, and escins, obtained from Aralia elata (bark, root cortex, young shoot), Kochia scoparia (fruit), Polygala senega var. latifolia (roots), Camellia japonica (seeds), and Aesculus hippocastanum (seeds), considering the following biofunctional activities: (1) inhibitory effects on elevated levels of blood alcohol and glucose in alcohol and glucose-loaded rats, respectively, (2) inhibitory effects on gastric emptying in rats and mice, (3) accelerative effects on gastrointestinal transit in mice, and (4) protective effects against gastric mucosal lesions in rats. In addition, we describe (5) suppressive effects of the extract and chakasaponins from Camellia sinensis (flower buds) on obesity based on inhibition of food intake in mice. The active saponins were classified into the following three types: (1) olean-12-en-28-oic acid 3-O-monodesmoside, (2) olean-12-ene 3,28-O-acylated bisdesmoside, and (3) acylated polyhydroxyolean-12-ene 3-O-monodesmoside. Furthermore, common modes of action, such as involvements of capsaicin-sensitive nerves, endogenous NO and PGs, and possibly sympathetic nerves, as well as common structural requirements, were observed. Based on our findings, a common mechanism of action might mediate the pharmacological effects of active saponins. It should be noted that the gastrointestinal tract is an important action site of saponins, and the role of the saponins in the gastrointestinal tract should be carefully considered.

The Protective Effect of Polysaccharide SAFP from Sarcodon aspratus on Water Immersion and Restraint Stress-Induced Gastric Ulcer and Modulatory Effects on Gut Microbiota Dysbiosis.

Sarcodon aspratus is a popular edible fungus for its tasty flavour and can be used as a dietary supplement for its functional substances. This study was conducted to evaluate the potential health benefits of Sarcodon aspratus polysaccharides (SAFP) on water immersion and restraint stress (WIRS)-induced gastric ulcer in rats. The results indicated that SAFP could decrease myeloperoxidase (MPO) activity and plasma corticosterone levels, as well as enhance Prostaglandin E2 (PGE2) and Nitrate/nitrite (NOx) concentration in rats. Furthermore, SAFP significantly attenuated the stress damage, inflammation, pathological changes and gastric mucosal lesion in rats. Moreover, high-throughput pyrosequencing of 16S rRNA suggested that SAFP modulated the dysbiosis of gut microbiota by enhancing the relative abundance of probiotics, decreasing WIRS-triggered bacteria proliferation. In summary, these results provided the evidence that SAFP exerted a beneficial effect on a WIRS-induced gastric ulcer via blocking the TLR4 signaling pathway and activating the Nrf2 signaling pathway. Notably, SAFP could modulate the WIRS-induced dysbiosis of gut microbiota. Thus, SAFP might be explored as a natural gastric mucosal protective agent in the prevention of gastric ulcers and other related diseases in the food and pharmaceutical industries.

Effect of Cuttlebone on Healing of Indomethacin-Induced Acute Gastric Mucosal Lesions in Rats.

The continuing use of nonsteroidal anti-inflammatory drugs (NSAIDs) usually increases the side effects such as peptic ulcer and acute gastric lesions in the gastrointestinal tract. Cuttlebone (CB), isolated from Sepiella maindroni de Rochebrune, was reported to have antioxidant activities, but its role in the treatment of indomethacin-induced gastric lesions has not yet been confirmed. In this research, we investigate the protective effect of cuttlebone on indomethacin-related ulcers in rats and possible mechanisms. Here, gastric ulcers were induced by oral administration of indomethacin, and then the rats were treated with omeprazole (4 mg/kg) or different doses (750, 1500, and 3000 mg/kg of body weight) of cuttlebone. We evaluated lesion index, inflammation score, and a series of oxidant/antioxidant parameters. The data demonstrated that cuttlebone could protect against gastric ulcers induced by indomethacin in a dose-dependent manner (positive correlation). Also, these effects were associated with attenuating the expression of malonaldehyde (MDA) and increasing the levels of some protective ingredients like epidermal growth factor (EGF), prostaglandin E2 (PGE2), and superoxide dismutase (SOD). Thus, considering its ability to protect indomethacin-induced acute gastric mucosal lesions and the underlying mechanisms, CB might be a potential candidate for treating gastric damage caused by NSAIDs.

Protective Effects of Wheat Peptides against Ethanol-Induced Gastric Mucosal Lesions in Rats: Vasodilation and Anti-Inflammation.

Alcohol consumption increases the risk of gastritis and gastric ulcer. Nutritional alternatives are considered for relieving the progression of gastric mucosal lesions instead of conventional drugs that produce side effects. This study was designed to evaluate the gastroprotective effects and investigate the defensive mechanisms of wheat peptides against ethanol-induced acute gastric mucosal injury in rats. Sixty male Sprague–Dawley rats were divided into six groups and orally treated with wheat peptides (0.1, 0.2, 0.4 g/kgbw) and omeprazole (20 mg/kgbw) for 4 weeks, following absolute ethanol administration for 1 h. Pretreatment with wheat peptides obviously enhanced the vasodilation of gastric mucosal blood vessels via improving the gastric mucosal blood flow and elevating the defensive factors nitric oxide (NO) and prostaglandin E2 (PGE2), and lowering the level of vasoconstrictor factor endothelin (ET)-1. Wheat peptides exhibited anti-inflammatory reaction through decreasing inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, and increasing trefoil factor 1 (TFF1) levels. Moreover, wheat peptides significantly down-regulated the expression of phosphorylated nuclear factor kappa-B (p-NF-κB) p65 proteins in the NF-κB signaling pathway. Altogether, wheat peptides protect gastric mucosa from ethanol-induced lesions in rats via improving the gastric microcirculation and inhibiting inflammation mediated by the NF-κB signaling transduction pathway.

The gastroprotective effect of the foxtail millet and adlay processing product against stress-induced gastric mucosal lesions in rats

Foxtail millet (Setaria italica (L.) P. Beauv.) and adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) seeds have substantial benefits possesses remarkable edible and nutritive values, and ease of processing and food manufacturing. They have nutraceutical properties in the form of antioxidants which prevent deterioration of human health and have long been used in traditional Chinese medicine as a remedy for many diseases. The present study is designed to investigate the gastroprotective effect of foxtail millet and adlay processing product (APP) diet on water immersion restraint stress (WIRS) induced ulceration in rats. We examined the effects of intake of AIN-93G diet containing either foxtail millet (10, 20 and 40%, 4 weeks) or APP (15 and 30%, 5 weeks) on macroscopic ulcer index (UI), plasma calcium level, lipid peroxidation products (estimated by the thiobarbituric acid reactive substances; TBARS), non-protein sulfhydryl (NPSH), digestive enzyme activities, and histopathology were determined. The results showed that pretreatment with millet and adlay diets significantly prevented the gastric mucosal lesion development. In addition, ulcerated rats showed depletion of NPSH levels whereas treatment with millet and adlay reverted this decline in stress-induced rats. Histological studies confirmed the results. The finding suggests that millet and adlay diets promote ulcer protection by the decrease in ulcer index, TBARS values and increase NPSH concentrations. Millet and adlay diets retain the advantage of being a natural product which may protect the gastric mucosa against ulceration.

Protective effect of Corchorus capsularis L. leaves on ethanol-induced acute gastric mucosal lesion in rats.

In Taiwan, Corchorus capsularis L. has long been cultivated and the leaves are consumed as edible vegetable. This study is to investigate the protection effect of extract of C. capsularis leaves (ECC) on ethanol-induced acute gastric mucosal lesion (AGML) in rats. The results of phytochemical determination in ECC for total polyphenol, flavonoid and polysaccharide were 59.88 ± 0.61 mg/g, 86.39 ± 18.0 mg/g and 320.89 ± 6.99 mg/g, respectively. ECC showed significant activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging with IC50 of 0.25 mg/ml. In vivo studies, Sprague-Dawley (SD) rats were randomly divided into five groups: sham, vehicle (control) and low-, medium-, and high-dose ECC (LECC, MECC, HECC; 200, 400, and 1,000 mg/kg/day, respectively). ECC was able to decrease significantly the ulcer index (UI) caused by 80% ethanol in a dose dependent manner. There was no significant effect on growth trend and food intake rate after the administration of ECC in the experimental period. The serum lipid parameters in ECC groups revealed significant increase in glutathione peroxidase (GPx), superoxide dilmutase (SOD) and catalase (CAT), and a decrease in malondialdehyde (MDA). Significant amelioration on pathological lesion score was found in ECC groups compared with the control group (P<0.05). The overall results indicate that ECC has protective effects on ethanol-induced AGML in rats, which could be associated with its antioxidant activity.

Protective effect of angiotensin II type 1 receptor antagonist against gastric mucosal lesions in rats with cerebral hemorrhage and acute stress gastric mucosal injury

Protective effect of angiotensin II type 1 receptor antagonist against gastric mucosal lesions in rats with cerebral hemorrhage and acute stress gastric mucosal injury

Time-effect relationship and molecular mechanism of electroacupuncture for repair of gastric mucosal lesion

To dynamically observe the effects of electroacupuncture (EA) on repair of gastric mucosal lesion in rats with gastric ulcer, and to explore the time-effect relationship and molecular mechanism of EA for gastric ulcer. A total of 72 SD rats were randomly assigned to a normal group, a model group, a acupoint group and a sham acupoint group, and each group were further divided into a 1-day subgroup, a 4-day subgroup and a 7-day subgroup, 6 rats in each subgroup. The rat model of gastric ulcer was established by using intragastric administration of ethyl alcohol. The rats in the acupoint group were treated with EA at"Zusanli"(ST 36) and"Liangmen"(ST 21); the rats in the sham acupoint group were treated with EA at points 5 mm next to"Zusanli"(ST 36) and"Liangmen"(ST 21); the EA was given 30 min per treatment, once a day. The rats in the normal group and model group were treated with immobilization for 30 min per day, and no EA was given. PR-PCR method was applied to test the expression of proliferating cell nuclear antigen (PCNA) and substance P (SP); Western blot method was applied to test the expression of neurotensin (NT). After 1-day treatment, the ulcer index in the model group was higher than that in the normal group (P<0.01), and the expression of PCNA, SP and NT was decreased (P<0.01, P<0.05); compared with the model group and sham acupoint group, the ulcer index was decreased in the acupoint group (both P<0.05), and the expression of PCNA and SP was up-regulated (all P<0.05) while that of NT was up-regulated (both P<0.01). After 4-day treatment, the ulcer index in the model group was reduced but still higher than that in the normal group (P<0.05), and the expression of PCNA, SP and NT was up-regulated and higher than that in the normal group (all P<0.01); the ulcer index in the acupoint group was similar to that in the normal group (P>0.05), and the expression of PCNA and SP was lower than that in the model group (P<0.01, P<0.05), and the expression of NT was not significantly different from that in the model group (P>0.05). After 7-day treatment, the differences of indexes above were not significant among the four groups (all P>0.05). EA at acupoints of stomach meridian has two-way regulation on PCNA and SP and improve the expression of NT in different pathological state of gastric ulcer, which could further improve the repair of gastric ulcer.

Gastroprotective effects of Tunisian green clay on ethanol-induced gastric mucosal lesion in rats

Natural green clay is mostly used in pharmaceutical and cosmetic products. The effect of this raw material from different outcrops around the world demonstrates its beneficial role on human health. The green clay from southern Tunisia is widely used in local traditional medicine and cosmetic preparations but its biological activity in vivo has not been studied yet. For this reason, this work was interested in deciphering the properties of the Tunisian green clay such as mineralogy composition and biological effect. In fact, the mineralogical study of this green clay shows two types of clay minerals such as illite and kaolinite with proportion of 75% and 25%, respectively. In order to study the biological effect, green clay was administered orally to rats for 1h at 50, 75, 100 and 125mg/kg doses. After that, ethanol 95% was given to these rats to induce a gastric ulcer. Then, several parameters (e.g. Ulcer index, protective rate, mucus production gastric and mucosa histology) were measured to evaluate the gastroprotective activity. The histology study shows normal gastric mucosa in rats pretreated at 75, 100 and 125mg/kg doses and the decrease of Ulcer Index (%I=97%) and lesions areas.The oral administing mixture of Tunisian green clay with ethanol in rats induces severe mucosal lesion and hemorrhagic bands. This clay colored by methylene blue shows that clay was linked to the mucus excreted by the stomach surface. The green clay didn't neutralize ethanol gastro toxicity and formed a layer on the gastric mucosa to protect it by a mechanical action. When investigated on rats at an effective dose treatment (75mg/kg) for 30days, the subchronic toxicity test of green clay did not reveal any signs of mortality and toxicity, and it demonstrated the normal hematological and biochemical parameters of rats.Thus, the Tunisian green clay can be considered as a safe natural product since it has a potential gastroprotective activity on ethanol induced gastric mucosal lesions in rats.

Protective effect of N,N'-dimethylthiourea against stress-induced gastric mucosal lesions in rats.

In the present study, we examined the protective effect of N,N'-dimethylthiourea (DMTU), a scavenger of hydroxyl radical (·OH), against water-immersion restraint stress (WIRS)-induced gastric mucosal lesions in rats. When male Wistar rats fasted for 24 h were exposed to WIRS for 3 h, gastric mucosal lesions occurred with increases in the levels of gastric mucosal myeloperoxidase (MPO), an index of tissue neutrophil infiltration, pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin 1beta), lipid peroxide (LPO), and nitrite/nitrate (NOx), an index of nitric oxide synthesis, and decreases in the levels of gastric mucosal nonprotein SH and vitamin C and gastric adherent mucus. DMTU (1, 2.5, or 5 mmol/kg) administered orally at 0.5 h before the onset of WIRS reduced the severity of gastric mucosal lesions with attenuation of the changes in the levels of gastric mucosal MPO, pro-inflammatory cytokines, LPO, NOx, nonprotein SH, and vitamin C and gastric adherent mucus found at 3 h after the onset of WIRS in a dose-dependent manner. Serum levels of corticosterone and glucose, which are indices of stress responses, increased in rats exposed to WIRS for 3 h, but DMTU pre-administered at any dose had no effect on these increases. These results indicate that DMTU protects against WIRS-induced gastric mucosal lesions in rats by exerting its antioxidant action including ·OH scavenging and its anti-inflammatory action without affecting the stress response.

English

The highly selective serotonin reuptake inhibitors are successful in the treatment of depression mood and anxiety disorders. The objective of this study is to investigate the effect of fluexotine and buspirone when given orally in three dose levels (5, 10 and 15 mg/ kg) not only for eight weeks on gastric lesions and oxidative markers in normal rats' mucosal integrity, but also for four weeks on gastric mucosal lesions in rats treated with indomethacin- induced ulcers. The results of this study showed that in normal rats, the administration of fluoxetine induced gastric lesions while buspirone caused no lesions. The indomethacin administration resulted in the development of gastric mucosal lesions. Furthermore, co-administration of fluoxetine and indomethacin enhanced the development of gastric mucosal lesions that were coupled with disturbance in antioxidant status. Buspirone, in contrast, significantly decreased the development of gastric mucosal lesions in rats treated with indomethacin. In conclusion, fluoxetine caused the development of gastric mucosal lesions and aggravate the effect of indomethacin to induce ulcer, however, buspirone had a protective effect that may be attributed to its antioxidant properties. Key words: Fluoxetine, buspirone, peptic ulcer, indomethacin-induced ulcer, oxidative stress.

Antioxidant Properties and Gastroprotective Effects of 2-(Ethylthio)Benzohydrazones on Ethanol-Induced Acute Gastric Mucosal Lesions in Rats.

A series of new 2-(ethylthio)benzohydrazone derivatives (1–6) were prepared and characterised by IR, 1H NMR, and 13C NMR spectroscopy and mass spectrometry. The newly prepared compounds were screened for their in vitro antioxidant activities using free radical scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Among them, most powerful antioxidant, compound 1 has been selected in order to illustrate anti-ulcer effect on ethanol-induced gastric mucosal lesions in rats. Four groups of Sprague Dawley rats were respectively treated with 10% Tween 20 as ulcer control group, 20 mg/kg omeprazole as reference group, 50 mg/kg and 100 mg/kg compound 1 as experimental animals. Macroscopically, ulcer control group showed extensive hemorrhagic lesions of gastric mucosa compared with omeprazole or compound 1. Rats pre-treated with compound 1 showed increased in gastric pH and gastric mucus. Histologically, ulcer control group showed severe damage to gastric mucosa with edema and leucocytes infiltration of submucosal layer. In immunohistochemical analysis, rats which were pre-treated with compound 1 showed up-regulation of HSP70 and down-regulation of Bax proteins. In conclusion, the gastroprotective effect of compound 1 may be due to its antioxidant activity, and/or due to up-regulation of HSP70 and down-regulation of Bax protein in stained tissue section.

Extrusion process of Acanthopanax senticosus leaves enhances the gastroprotective effect of compound 48/80 on acute gastric mucosal lesion in rats

ObjectiveTo investigate the gastroprotective effects of Acanthopanax senticosus leaves (ASLs) extrusion on acute gastric mucosal lesion in rats induced by compound 48 / 80 (C48 / 80). MethodsRats were divided into six groups: normal; C48/80-induced gastric lesion control; gastric lesion positive control (famotidine 4 mg/kg); gastric lesion administered with two levels of extruded ASLs (ASLE, 40 and 200 mg/kg); and gastric lesion treated with ASLs (ASL 200 mg/kg). Mucus secretion / damage was determined by immunohistological staining. Immunofluorescence and western blotting were performed to determine gastric mucosal Bax and Bcl-2 expression. Gastric mucosal oxidative-stress-related enzymes and malondialdehyde were determined. ResultsC48/80-induced mucus depletion and inflammation in the gastric mucosa were significantly attenuated by ASLs. The increased serum serotonin and histamine concentrations in C48/80-treated rats were also attenuated by ASLs. Gastric mucosal Bax protein expression was increased and Bcl-2 expression was decreased after C48/80 treatment, and ASLs ameliorated Bax and Bcl-2 expression. The extrusion process significantly augmented the effects of ASLs in a dose-dependent manner. ASLEs at 200 mg/kg normalized mucus damage / secretion, C48 / 80-induced increases of mucosal myeloperoxidase activity (index of inflammation), xanthine oxidase, and malondialdehyde content (index of lipid peroxidation). The effects of ASLs on Bax and Bcl-2 expression were also enhanced by extrusion. Furthermore, these effects of ASLEs at 200 mg/kg were similar to those of famotidine, a histamine H2-receptor antagonist commonly used to treat gastric ulcers. ConclusionASLEs prevented acute gastric mucosal lesion progression induced by C48/80, possibly by inducing mucus production, and reduced inflammation and oxidative stress in gastric mucosa through an anti-apoptotic mechanism.

Effects of Yifukang Oral Liquid on Chemotherapy- and Radiotherapy-Induced Toxic and Side Effects of Myelosuppression, Leucopenia and Gastrointestinal Tract Disturbances

Purpose: To investigate the effects of Yifukang oral liquid (YFKOL) on chemotherapy- and radiotherapy-induced myelosuppression, leucopenia and gastrointestinal tract disturbances. Methods: The effects of YFKOL on myelosuppression, leucopenia and gastrointestinal tract disturbances were assessed by cyclophosphamide- and Co60-induced leucopenia in mice, copper sulfate-induced emesis in pigeons, ethanol-induced gastric mucosal lesions in rats, gastric emptying and intestinal propulsion in mice. Results: In cyclophosphamide- and Co60-induced leucopenia assays, the mean white blood cell count (82.6 and 90.1 × 10 9 /L; 7.3 and 8.2 × 10 9 /L, respectively) and thighbone marrow granulocytes (66.1 % and 67.4 %; 60.8 and 66.5 %, respectively) were significantly (p < 0.05) increased after treatment with YFKOL (15 and 30 mL/kg), compared with the respective control (68.2 and 4.7 × 10 9 /L; 58.2 and 53.1 %). In emesis, gastric mucosal lesions, gastric emptying and intestinal propulsion assays, the mean frequency of emesis (30.8 and 22.3 times, respectively) and ulcer index (39.6 and 26.5, respectively) significantly (p < 0.05) decreased, and the mean gastric emptying (25.0 and 24.0 %) and intestinal propulsion (81.9 and 82.8 %) were significantly (p < 0.05) promoted after treatment with YFKOL (10 and 20 mL/kg), compared with the respective control (54.7 times, 62.8, 42.0 and 68.9 %). Conclusion: YFKOL may suppress chemotherapy- and radiotherapy-induced myelosuppression, leucopenia and gastrointestinal tract disturbances. Keywords: Yifukang oral liquid, Gastrointestinal tract disturbances, Leucopenia, Myelosuppression, Tumor, Chemotherapy, Radiotherapy

Evaluation of gastroprotective activity of Passiflora alata

Passiflora alata Curtis, Passifloraceae, is a liana popularly known in Brazil as ‘maracujá-doce’ that has been used for treating different illnesses. Its leaves are described in the Brazilian Pharmacopoeia, but the gastroprotective activity has never been investigated. In the present study a freeze-dried crude 60% ethanol–water extract of P. alata aerial parts was prepared. Total flavonoid content, expressed as vitexin, was 0.67%±0.01. The hemolytic activity was 32 units for P. alata, using Saponin (Merck®) as reference. P. alata presented EC50 of 1061.2±8.5μg/ml in the 2,2-diphenyl-1-picryhydrazyl assay and 1076±85μmol Trolox/g in the Oxygen Radical Absorbance Capacity assay. P. alata, its solvent fractions and a P. alata nanopreparation were investigated for gastroprotective activity. The test samples exhibited gastroprotective activity on HCl/ethanol induced gastric mucosal lesions in rats. P. alata at doses of 100, 200 and 400mg/kg, using the necrotizing agent at 150mmol/l, inhibited 100% of ulcer formation (compared to the negative control), while lansoprazole (30mg/kg) 77%. When tested against a more concentrated necrotizing agent (300mmol/l), fractions of P. alata at 100mg/kg reduced 57% (n-hexane), 34% (ethyl acetate) and 72% (aqueous fraction) the ulcer formation. In this assay, lansoprazole (30mg/kg) inhibited 47%. When encapsulated, P. alata inhibited ulcer formation at 55%, 94% and 90% for dosages of 25, 50 and 100mg/kg. These results suggest the potential use of P. alata as a gastroprotective herbal medicine.

Ghrelin gene expression in rats with ethanol-induced gastric ulcers: arole of melatonin.

The aim of the present work was to reveal the mechanisms of melatonin treatment on ethanol-induced gastric mucosal lesions in rats, including its role in the induction of ghrelin biosynthesis. Sixty male Wistar rats were divided into 3 groups (20 in each group): a) control group, b) ulcer group (100% ethanol was given intragastrically (i.g.) in a dose of 1 ml/100 g of body weight), and 3) melatonin-treated group, which received a single dose (25 mg/kg) of melatonin (Biovea) i.g. 30 min before ulcer induction with ethanol. Reduced glutathione (GSH) and malondialdehyde (MDA) were measured in tissues and ghrelin levels determined in the serum. RNA isolation and RT-PCR expression of ghrelin were performed. Both macroscopic and microscopic examinations of gastric mucosa were done in all groups. Significant decrease in ghrelin levels and mRNA expression and reduced levels of GSH were observed in ulcer group of rats in comparison with controls. All parameters studied were significantly increased after treatment with melatonin in comparison with ulcer bearing group of rats. On the other hand, the tissue levels of MDA were significantly increased in ulcer group of rats in comparison with controls and significantly decreased after melatonin treatment in comparison with the ulcer group of rats. Histological examinations revealed severe mucosal lesions induced by ethanol which were significantly improved by melatonin administration. The present data indicate that melatonin may have a potential impact in the treatment of peptic ulcer not only via its known antioxidant effect but also via induction of the ghrelin biosynthesis, as it was documented by significant increase in ghrelin mRNA expression.

Remote ischemic postconditioning protects against gastric mucosal lesions in rats.

To investigate the protective effects of remote ischemic postconditioning (RIP) against limb ischemia-reperfusion (IR)-induced gastric mucosal injury. Gastric IR was established in male Wistar rats by placing an elastic rubber band under a pressure of 290-310 mmHg on the proximal part of both lower limbs for 3 h followed by reperfusion for 0, 1, 3, 6, 12 or 24 h. RIP was performed using three cycles of 30 s of reperfusion and 30 s of reocclusion of the femoral aortic immediately after IR and before reperfusion for up to 24 h. Rats were randomly assigned to receive IR (n = 36), IR followed by RIP (n = 36), or sham treatment (n = 36). Gastric tissue samples were collected from six animals in each group at each timepoint and processed to determine levels of malondialdehyde (MDA), superoxide dismutase (SOD), xanthine oxidase (XOD) and myeloperoxidase (MPO). Additional samples were processed for histologic analysis by hematoxylin and eosin staining. Blood samples were similarly collected to determine serum levels of lactate dehydrogenase (LDH), creatine kinase (CK), tumor necrosis factor (TNF)-α and interleukin (IL)-10. The pathologic changes in gastric tissue induced by IR were observed by light microscopy. Administration of RIP dramatically reduced the gastric damage score after 6 h of reperfusion (5.85 ± 0.22 vs 7.72 ± 0.43; P < 0.01). In addition, RIP treatment decreased the serum activities of LDH (3.31 ± 0.32 vs 6.46 ± 0.03; P < 0.01), CK (1.94 ± 0.20 vs 4.54 ± 0.19; P < 0.01) and the concentration of TNF-α (53.82 ± 0.85 vs 88.50 ± 3.08; P < 0.01), and elevated the concentration of IL-10 (101.46 ± 5.08 vs 99.77 ± 4.32; P < 0.01) induced by IR at 6 h. Furthermore, RIP treatment prevented the marked elevation in MDA (3.79 ± 0.29 vs 6.39 ± 0.81) content, XOD (7.81 ± 0.75 vs 10.37 ± 2.47) and MPO (0.47 ± 0.05 vs 0.82 ± 0.03) activities, and decrease in SOD (4.95 ± 0.32 vs 3.41 ± 0.38; P < 0.01) activity in the gastric tissue as measured at 6 h. RIP provides effective functional protection and prevents cell injury to gastric tissue induced by limb IR via anti-inflammatory and antioxidant actions.

Gastro Protective, Antiapoptotic and Anti-inflammatory Effect of Alpha-lipoic Acid on Ethanol Induced Gastric Mucosal Lesions in Rats

Gastro Protective, Antiapoptotic and Anti-inflammatory Effect of Alpha-lipoic Acid on Ethanol Induced Gastric Mucosal Lesions in Rats