Ethanol-induced Gastric Lesions Research Articles

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Preparation, Characterization and Anti-Ulcer Efficacy of Sanguinarine Loaded Solid Lipid Nanoparticles

Aim: This study was designed to develop sanguinarine-loaded solid lipid nanoparticles (SG-SLNs) and investigate its gastroprotective effect on ethanol-induced gastric mucosal lesions in mice. Methods: SG-SLNs were prepared by high temperature melt-cool solidification method using glycerol monostearate as the lipid and a combination of lecithin with poloxamer 188 as the surfactants. Solid lipid nanoparticles (SLNs) were designed at varying lipid concentrations (5, 10, 15, and 20 mg/mL), surfactant mixture concentrations (6, 12, and 18 mg/mL), and drug contents (5, 10, 15, and 20 mg/mL) in “one factor at a time” fashion. Ethanol-induced gastric ulcer model was performed on Kunming mice to examine the anti-inflammatory activity of SG-SLNs and compare it with sanguinarine (SG). Results: The high temperature melt-cool solidification method provided consistent production of SLNs with smaller size and high entrapment efficiency (EE%). The composition of optimal formulation was 10 mg/mL lipid concentration, 18 mg/mL surfactant mixture concentration, and 15 mg/mL drug amount. The mean particle size and EE% of optimized formulation were 238 ± 10.9 nm and 79 ± 2.8%, respectively. Additionally, SG-SLNs significantly decreased tumor necrosis factor-alpha and interleukin-6 levels in the serum and gastric tissue, and reduced the content of NO in serum, and strengthened the protection of mucosal membrane. Moreover, SG-SLNs treatment markedly inhibited ethanol-induced nuclear factor-kappa B (NF-κB) activation when compared with SG. Conclusions: SLNs could be potentially applied as a delivery system of SG. The protective effect of SG-SLNs is due to the suppression of NF-κB expression and subsequent pro-inflammatory cytokines release.

Gastroprotective effect of esculin on ethanol-induced gastric lesion in mice.

The gastroprotective effect of esculin was investigated in a mouse model of ethanol-induced gastric lesion. Administration of esculin at doses of 5, 10, and 20 mg/kg body weight prior to ethanol ingestion led to significant gastroprotection compared with untreated mice. Gastric mucosal lesions were evaluated by macroscopic and histopathological alterations, lesion index, and myeloperoxidase (MPO) activity. Pretreatment with esculin significantly reduced macroscopic and histopathological damage, gastric lesion index, and MPO activity in a dose-dependent manner. Moreover, esculin significantly reduced nitric oxide (NO) production, inducible NO synthase (iNOS) levels, and nuclear factor-kappa B (NF-κB) p65 protein expression in gastric tissues after ethanol challenge. Analysis of inflammatory cytokines indicated that esculin pretreatment markedly suppressed the increased expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in ethanol-treated mice. The results demonstrate a protective effect of esculin against gastric injury and suggest that the underlying mechanism might be associated with inhibition of NF-κB activation, which subsequently reduces expression of iNOS, TNF-α, and IL-6.

Short Chain Fatty Acid Acetate Protects against Ethanol-Induced Acute Gastric Mucosal Lesion in Mice.

Short chain fatty acids acetate and propionate have been demonstrated protective function in the intestinal mucosa. However, their impact on gastric mucosa has not yet been elucidated. The current study aimed to investigate the potential protective effects of acetate and propionate against ethanol-induced gastric mucosal lesion and the underlying mechanism in mice. ICR mice were orally treated with acetate and propionate, respectively, 30 min prior to the establishment of gastric mucosal injury model by challenge with absolute ethanol. The gastric samples were collected for the detection of oxidative, inflammatory and apoptotic related parameters. Acetate, but not propionate, attenuated the severity of gastric mucosal damage as evidenced by the gross changes of gastric mucosa, pathological aberrations. Acetate alleviated oxidative stress as shown by the increase in glutathione (GSH) content and superoxide dismutase (SOD) activities, and the decrease of malondialdehyde (MDA) level. The elevated concentrations of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6, and the activation of nuclear factor-kappaB (NF-κB) p65 by ethanol stimulation was also reduced by acetate. Moreover, the anti-inflammatory factors, IL-4, LXA4 and IL-10, were up-regulated in acetate treated group. With respect to gastric mucosal apoptosis, acetate suppressed caspase-3 activity and BAX expression in favor of cell survival. These favorable actions were maybe associated with up-regulation of the gastric MUC5AC, the key defense factor of gastric mucosal system. These findings accentuate the gastroprotective actions of acetate in ethanol-induced gastric injury which were mediated via concerted multi-prolonged actions, including suppression of gastric oxidation, inflammation and apoptosis and promotion of MUC5AC expression.

Gastroprotection of 2,3-epoxyjuanislamin, Isolated from Calea urticifolia, Against Ethanol-induced Gastric Lesions in Wistar Rats

Gastroprotection of 2,3-epoxyjuanislamin, Isolated from Calea urticifolia, Against Ethanol-induced Gastric Lesions in Wistar Rats

Gastroprotective potential of melatonin versus melatonin loaded niosomes on gastric ulcer healing in rats

The present study was conducted to investigate the therapeutic effects of melatonin and melatonin-loaded niosomes on ethanol-induced gastric lesions. Morphological and biochemical changes associated with each drug were investigated. Seventy apparently healthy female albino rats, weighting about 200–250 g were randomly assigned to 4 experimental groups. The first group (induction group) included 10 rats that were given 1 ml 70 % ethanol and sacrificed after 1 and 1/2 hour. The second group (melatonin-treated group) included 25 rats that were administrated with 2 mg/rat melatonin by gastric tube daily after induction of ulcer by ethanol. Five rats were sacrificed after 3, 7, 14, 21, and 28 days post-treatment. The third group (melatonin-loaded niosomes treated group) consisted of 25 rats that were given melatonin-loaded niosomes in the same dose and route as the third group. Five rats were sacrificed after 3, 7, 14, 21, and 28 days post-treatment. The fourth group (control group) consisted of 10 rats that administrated only the vehicle in a similar dose and route as other groups (5 rats were given 1 ml of saline and the other 5 rats were given 1 ml of niosomes polymer daily via gastric tube). The rats were kept throughout the time of the study and were sacrificed by cervical dislocation at the end of the experiment. Gross lesions were carried out, and ulcer index was calculated for each subgroup. Tissue samples were fixed in 10 % neutral buffered formalin and stained with Hx&E stain for conventional histological examination. Biochemical analysis of tissue homogenate for determination of lipid peroxidation and total antioxidants was performed. Melatonin-loaded niosomes showed early impressive gastroprotection as early as 7 days post-treatment while unloaded melatonin therapy exerted their effects after 14 days respectively. In addition, melatonin-loaded niosomes improved the micro-vascular damages after 14 days compared to the other melatonin-treated group which showed improved gastric alterations after 21 days. Biochemically, the cases of melatonin-loaded niosomes achieved the lowest mean values of lipid peroxidation and highest mean values of total antioxidants compared to other values recorded in case of unloaded melatonin therapy, and these results are in accordance with that of the histopathological findings.

Gastroprotective effects of 1-Hydroxy-2-phenylbenzimidazole in ethanol-induced gastric ulcers in rats

Abstract Introduction: Benzimidazole compounds are known for their reduction of gastric secretion by inhibition of H+/K+-ATPase enzyme. Aim: The gastroprotective activity of the synthesized 1-hydroxy-2-phenylbenzimidazole (HPB) is examined on gastric lesions induced in rats by the oral ingestion of ethanol. Methods: Gastroprotective activity was evaluated by estimation of the numbers and cumulative lengths of glandular gastric ulcers induce by ethanol. The effect of pretreatment with HPB given alone and in combination with ranitidine on the number and length of gastric ulcers; and as well as on gastric volume and total gastric acidity were investigated. Results: Pre-treatment of rats with HPB at the doses of 25 and 50 mg/kg IP, significantly decreased the number and the length of ethanol induced gastric ulcers compared to control group. The highest curative ratio 53.89% and the most reduction of gastric acidity were obtained with the highest dose of HPB (50 mg/kg) in combination with ranitidine. Histopathological findings confirmed the protective effect of the HPB. Conclusion: The synthesized benzimidazole derivative (HPB) provided a gastroprotective effects on ethanol-induced gastric lesions in rats. This protective activity may be partly due to its ability to attenuate acid secretion.

Gastroprotective effect of (-)-myrtenol against ethanol-induced acute gastric lesions: possible mechanisms.

(-)-Myrtenol is a natural fragrance monoterpenoid structurally related to α-pinene found in diverse plant essential oils. This study was aimed to assess the anti-ulcerogenic potential of (-)-myrtenol against ethanol-induced gastric lesions and to elucidate the underlying mechanism(s). Gastroprotective activity of (-)-myrtenol was evaluated using the mouse model of ethanol-induced gastric damage. To elucidate the gastroprotective mechanism(s), the roles of GABA, prostaglandins, nitric oxide and KATP channels were assessed. Besides, the oxidative stress-related parameters and the mucus content in gastric tissues were analysed. (-)-Myrtenol at oral doses of 25, 50 and 100 mg/kg significantly decreased the severity of ethanol-induced gastric lesions affording gastroprotection that was accompanied by a decrease in the activity of myeloperoxidase and malondialdehyde, an increase in GPx, SOD, and catalase activity in gastric tissues, and with well-maintained normal levels of nitrite/nitrate, gastric mucus and NP-SHs. Pretreatment with GABA-A receptor antagonist flumazenil, the COX inhibitor indomethacin, and NO synthesis inhibitor L-NAME but not with KATP channel blocker glibenclamide significantly blocked the (-)-myrtenol gastroprotection. These results provide first-time evidence for the gastroprotective effect of (-)-myrtenol that could be related to GABAA -receptor activation and antioxidant activity.

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.

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.

The Protective Effect of a <i>Puerariae flos</i> Extract (Thomsonide) against Ethanol-Induced Gastric Lesions in Rats

Objectives: Puerariae flos has popularly been used to treat alcoholic disorders. However, the effect of Puerariae flos on alcoholic disorders in the gastrointestinal system has not been identified. We investigated the protective effect of an extract of Puerariae flos against the murine gastric mucosa. Methods: Thomsonide, the extracts containing large amounts of isoflavonoid and triterpenoid saponin, was obtained fr om Puerriae flos via Diaion HP-20 column chromatography using water and 99.5% ethanol. It was investigated whether thomsonide, as well as geranylgeranylacetone (teprenone), a popular anti-ulcer agent developed in Japan, had a cytoprotective effect that might be related to endogenous prostaglandins, which played an important role in preventing gastric mucosal lesions. Results: Thomsonide and teprenone inhibited ethanol-induced gastric lesions. Furthermore, thomsonide increased the production of PGE2 and 6-ketoPGF1α, a stable metabolite of PGI2, in the gastric mucosa, and protective effects of thomsonide, as well as teprenone, against ethanol-induced gastric lesions were attenuated by pretreatment with indomethacin. Conclusions: These findings suggest that thomsonide, as well as teprenone, has the gastro protective effect which may be related to the cytoprotective activity of endogenous prostaglandins. The results of this study also suggest that the gastro protective effect of thomsonide may partially mitigate alcoholic disorders in the gastrointestinal tract, and support our pharmacological belief that Puerariae flos is useful for treatment of alcoholic disorders.

Protective effect of trillin against ethanol-induced acute gastric lesions in an animal model

The purpose of the present study was to evaluate gastroprotective effect of trillin on mucosal lesions induced by ethanol.

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.

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.

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

The gastroprotective effects of hydroalcoholic extract of Monolluma quadrangula against ethanol-induced gastric mucosal injuries in Sprague Dawley rats.

Monolluma quadrangula (Forssk.) Plowes is used in Saudi traditional medicines to treat gastric ulcers. The hydroalcoholic extract of M. quadrangula (MHAE) was used in an in vivo model to investigate its gastroprotective effects against ethanol-induced acute gastric lesions in rats. Five groups of Sprague Dawley rats were used. The first group was treated with 10% Tween 20 as a control. The other four groups included rats treated with absolute ethanol (5 mL/kg) to induce an ulcer, rats treated with 20 mg/kg omeprazole as a reference drug, and rats treated with 150 or 300 mg/kg MHAE. One hour later, the rats were administered absolute ethanol (5 mL/kg) orally. Animals fed with MHAE exhibited a significantly increased pH, gastric wall mucus, and flattening of the gastric mucosa, as well as a decreased area of gastric mucosal damage. Histology confirmed the results; extensive destruction of the gastric mucosa was observed in the ulcer control group, and the lesions penetrated deep into the gastric mucosa with leukocyte infiltration of the submucosal layer and edema. However, gastric protection was observed in the rats pre-fed with plant extracts. Periodic acid–Schiff staining of the gastric wall revealed a remarkably intensive uptake of magenta color in the experimental rats pretreated with MHAE compared to the ulcer control group. Immunohistochemistry staining revealed an upregulation of the Hsp70 protein and a downregulation of the Bax protein in rats pretreated with MHAE compared with the control rats. Gastric homogenate showed significantly increased catalase and superoxide dismutase, and the level of malondialdehyde (MDA) was reduced in the rats pretreated with MHAE compared to the control group. In conclusion, MHAE exhibited a gastroprotective effect against ethanol-induced gastric mucosal injury in rats. The mechanism of this gastroprotection included an increase in pH and gastric wall mucus, an increase in endogenous enzymes, and a decrease in the level of MDA. Furthermore, protection was given through the upregulation of Hsp70 and the downregulation of Bax proteins.

Ulcer healing and mechanism(s) of action involved in the gastroprotective activity of fractions obtained from Syngonanthus arthrotrichus and Syngonanthus bisulcatus.

BackgroundSyngonanthus arthrotrichus and Syngonanthus bisulcatus, currently known for Comanthera aciphylla (Bong.) L.R.Parra & Giul. and Comanthera bisulcata (Koern.) L.R. Parra & Giul, popularly known in Brazil as “sempre-vivas,” are plants from the family Eriocaulaceae. They are found in the states of Minas Gerais and Bahia. The species are known to be rich in flavonoids to which their gastroprotective activity has been attributed. In this research, experimental protocols were performed to elucidate the associated mechanisms of action.MethodsThe activity was evaluated using induced gastric ulcer models (acetic acid and ethanol-induced gastric lesions in NEM or L-NAME pre-treated mice, and by ischemia/reperfusion). Antioxidant enzymes, serum somatostatin, and gastrin were also evaluated.ResultsIn chronic gastric ulcers, a single daily oral dose of Sa-FRF or Sb-FRF (100 mg/kg body wt.) for 14 consecutive days accelerated ulcer healing to an extent similar to that seen with an equal dose of cimetidine. The pre-treatment of mice with NEM (N-ethylmaleimide) or L-NAME (N-nitro-L-arginine) abolished the protective activity of Sa-FRF, Sa-FDF, Sb-FDF and Sb-FRF or Sa-FRF and Sb-FRF, respectively, which indicates that antioxidant compounds and nitric oxide synthase activity are involved in the gastroprotective. Sa-FRF and Sb-FRF (100 mg/kg p.o) protected the gastric mucosa against ulceration that was induced by ischemia/reperfusion (72 and 76 %, respectively). It also decreased lipid peroxidation and restored total thiols in the gastric wall of mice that had been treated with ethanol. When administered to rats submitted to ethanol-induced gastric lesions, Sa-FRF and Sb-FRF (100 mg/kg, p.o.) increased the somatostatin serum levels, while the gastrin serum levels were proportionally decreased.ConclusionsThe results indicate significant healing effects and gastroprotective activity for the Sa-FRF and Sb-FRF, which probably involves the participation of SH groups, nitric oxide (NO), the antioxidant system, somatostatin, and gastrin. All are integral parts of the gastrointestinal mucosa’s cytoprotective mechanisms against aggressive factors.

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.

Carbon Monoxide (CO) Released from Tricarbonyldichlororuthenium (II) Dimer (CORM-2) in Gastroprotection against Experimental Ethanol-Induced Gastric Damage.

The physiological gaseous molecule, carbon monoxide (CO) becomes a subject of extensive investigation due to its vasoactive activity throughout the body but its role in gastroprotection has been little investigated. We determined the mechanism of CO released from its donor tricarbonyldichlororuthenium (II) dimer (CORM-2) in protection of gastric mucosa against 75% ethanol-induced injury. Rats were pretreated with CORM-2 30 min prior to 75% ethanol with or without 1) non-selective (indomethacin) or selective cyclooxygenase (COX)-1 (SC-560) and COX-2 (celecoxib) inhibitors, 2) nitric oxide (NO) synthase inhibitor L-NNA, 3) ODQ, a soluble guanylyl cyclase (sGC) inhibitor, hemin, a heme oxygenase (HO)-1 inductor or zinc protoporphyrin IX (ZnPPIX), an inhibitor of HO-1 activity. The CO content in gastric mucosa and carboxyhemoglobin (COHb) level in blood was analyzed by gas chromatography. The gastric mucosal mRNA expression for HO-1, COX-1, COX-2, iNOS, IL-4, IL-1β was analyzed by real-time PCR while HO-1, HO-2 and Nrf2 protein expression was determined by Western Blot. Pretreatment with CORM-2 (0.5–10 mg/kg) dose-dependently attenuated ethanol-induced lesions and raised gastric blood flow (GBF) but large dose of 100 mg/kg was ineffective. CORM-2 (5 mg/kg and 50 mg/kg i.g.) significantly increased gastric mucosal CO content and whole blood COHb level. CORM-2-induced protection was reversed by indomethacin, SC-560 and significantly attenuated by celecoxib, ODQ and L-NNA. Hemin significantly reduced ethanol damage and raised GBF while ZnPPIX which exacerbated ethanol-induced injury inhibited CORM-2- and hemin-induced gastroprotection and the accompanying rise in GBF. CORM-2 significantly increased gastric mucosal HO-1 mRNA expression and decreased mRNA expression for iNOS, IL-1β, COX-1 and COX-2 but failed to affect HO-1 and Nrf2 protein expression decreased by ethanol. We conclude that CORM-2 released CO exerts gastroprotection against ethanol-induced gastric lesions involving an increase in gastric microcirculation mediated by sGC/cGMP, prostaglandins derived from COX-1, NO-NOS system and its anti-inflammatory properties.

Gastroprotective Activity of Methyleugenol from Peperomia hispidula on Ethanol-Induced Gastric Lesions in Rats

Gastroprotective Activity of Methyleugenol from Peperomia hispidula on Ethanol-Induced Gastric Lesions in Rats