Protective effect of (+)-catechin against gastric mucosal injury induced by ischaemia-reperfusion in rats

Ischaemia and reperfusion are known to induce gastric lesions, predominantly due to excessive formation of reactive oxygen metabolites, adhesion of neutrophils to endothelial cells, microvascular dysfunction, gastric acid secretion, endogenous histamine and gastrin release. We have studied the effect of (+)-catechin on a gastric ulcer model involving damage to gastric injury by ischaemia- reperfusion (I/R) in rats. (+)-Catechin 50 mg kg(-1)administered orally, once daily for three days after the initiation of I/R injury showed a significant (P<0.001) anti-ulcer activity against mucosal dam- age. However, (+)-catechin significantly decreased the lipid peroxidation and increased the level of catalase in the I/R condition. Elevated levels of alkaline phosphatase in the I/R group was significantly lowered (P<0.01) by (+)-catechin. The amount of H(+)K(+)ATPase was significantly decreased (P<0.001) in (+)-catechin-treated as compared with I/R rats. (+)-Catechin significantly decreased elevated plasma histamine (P<0.05) and corticosterone (P<0.05). The results suggested that (+)-catechin protected gastric mucosa against ischaemia-reperfusion-induced gastric ulcers by its antioxidant activity and mucus protection.     

Effect of teprenone on gastric mucosal injury induced by Helicobacter pylori in rats

The aim of this study was to investigate the protective effect of gastric mucus against Helicobacter pylori-induced gastric mucosal injury, measuring intramucosal mucus and the surface hydrophobicity. Male Sprague-Dawley rats' stomachs were exposed to H. pylori suspension (1 x 10(5) ml) plus 1 ml of urea solution (400 mg/dl) with gastric ischemia (withdrawal of 3 ml of blood) for 60 min, 60 min after pretreatment with teprenone (CAS 6809-52-5) (50 mg/rat, intragastric). The control rats were treated in the same manner without pretreatment with teprenone. A high concentration of intragastric ammonia was generated 60 min after administration of H. pylori plus urea in both the control and the teprenone-pretreated rats. A reduction in transmucosal potential difference, formation of hemorrhagic gastric lesions, and impairment in both intramucosal mucus and surface hydrophobicity were observed in the corpus of the control rats. However, the pretreatment with teprenone prevented such a reduction in potential difference and the development of gastric lesions against ammonia through the preservation of gastric mucus. The preservation of gastric mucus might protect gastric mucosa against attacks by H. pylori, suggesting that the mechanism of H. pylori-associated gastric injury is associated with the decrease in gastric mucus.     

芦丁对大鼠胃缺血再灌注损伤的保护作用

目的：研究芦丁对胃缺血再灌注损伤的保护作用及其机制。方法采用大鼠胃缺血再灌注损伤模型,观察胃黏膜细胞形态学变化;测定胃壁黏液含量、胃黏膜组织中一氧化氮（NO）含量、丙二醛（MDA）含量及超氧化物歧化酶（SOD）活性、髓过氧化物氧化酶（MPO）活性、总 NOS （TNOS）、诱导型（iNOS）和结构型 NOS （cNOS）活性。结果芦丁能显著降低胃黏膜损伤指数,维持胃黏膜缺血再灌注期 SOD 活力,降低 TNOS 和 iNOS 活性,上调 cNOS 活性,减少 MDA 含量,降低 MPO 活性,增加胃壁黏液分泌量,减轻缺血再灌注后胃黏膜病理损伤。结论芦丁对缺血再灌注引起的胃黏膜损伤具有保护作用,其作用机制可能与调节 NOS 活性,抑制淋巴细胞在胃黏膜组织中浸润,清除和抑制胃缺血再灌注时氧自由基产生,促进胃壁黏液分泌等机制有关。     

Role of nitric oxide in gastric injury induced by hemorrhagic shock in rats

The aim of this study was to investigate the effect of nitric oxide (NO) on the gastric injury induced by hemorrhagic shock. Hemorrhagic shock was created by withdrawing 3 ml blood/200 g body weight of the rats. Before the hemorrhage, N(G)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg i.v. bolus), D-NAME (10 mg/kg i.v. bolus), or L-arginine (100 mg/kg i.v. bolus and 10 mg/kg/min infusion) + L-NAME were administered. At the end of the 1-hour hypovolemic shock period, histological analysis, gastric ulcer index, gastric myeloperoxidase (MPO) activity, and gastric protein oxidation (PO) levels were determined. In histological analysis a destructive effect of L-NAME (NO synthase inhibitor) was demonstrated. L-NAME treatment increased gastric MPO activity, L-arginine reversed this effect and D-NAME had no effect. Tissue PO activity was found to be increased in L-NAME-treated rats; L-arginine treatment reversed this activity. It is concluded that gastric barrier function is altered after hemorrhagic shock, and L-arginine (NO precursor) can prevent mucosal injury in the stomach. This effect of NO may be on gastric blood flow and can be mediated by tissue neutrophils.     

Role of nitric oxide and mucus in ischemia/reperfusion-induced gastric mucosal injury in rats

The present study aims at investigating the role of nitric oxide (NO) on the oxidative damage in gastric mucosa of rats which received ischemia/reperfusion (I/R) and its relation to mucus. NO synthesis modulators such as L-arginine and N(G)-nitro-L-arginine methyl ester (L-NAME) were injected intraperitoneally to the rats 30 min prior to I/R which was induced by clamping the celiac artery and the superior mesenteric artery for 30 min and reperfusion for 1 h. As a result, I/R increased lipid peroxide production and decreased the contents of glutathione (GSH), cGMP and mucus as well as GSH peroxidase activities of gastric mucosa. I/R decreased the activity and protein of NO synthase (NOS) in gastric mucosa. Pretreatment of L-arginine, a substrate for NOS, prevented I/R-induced alterations of gastric mucosa. However, L-NAME, an NOS inhibitor, deteriorated oxidative damage induced by I/R. In conclusion, NO has an antioxidant defensive role on gastric mucosa by maintaining mucus, GSH and GSH peroxidase, which were related to preservation of cGMP and NOS in gastric mucosa.     

牛磺酸对乙醇性胃粘膜损伤的保护机制初探

目的为了探讨牛磺酸抗乙醇性胃粘膜损伤的作用机制。方法采用大鼠实验性乙醇胃粘膜损伤模型，测定胃粘膜局部一氧化氮合成酶（ＮＯＳ）、内皮素（ＥＴ）和部分胃肠激素含量。结果牛磺酸可明显减轻胃粘膜损伤，抑制ＥＴ释放，增加ＮＯＳ活性及生长抑素（ＳＳ）和血管活性肠肽（ＶＩＰ）的含量。结论牛磺酸可明显减轻实验性乙醇胃粘膜损伤，其可能机制为调节胃粘膜局部ＥＴ、ＮＯＳ、ＳＳ、ＶＩＰ的活性和含量。     

Effect of melatonin and beta-carotene on indomethacin induced gastric mucosal injury

The study was conducted to examine the role of free radicals in Indomethacin induced gastric mucosal injury and to evaluate the gastroprotective effects of melatonin and beta-carotene. Gastric mucosal injury was produced in rats by administering indomethacin 30 mg/kg subcutaneously. Melatonin was administered in three different doses of 5, 10 and 20 mg/kg, 30 minutes prior to the administration of indomethacin. Beta-carotene was administered as a single dose of 100 mg/kg. Following parameters were calculated: ulcer index, lipid peroxidation and antioxidant defense enzymes i.e. superoxide dismutase, glutathione peroxidase and catalase. Indomethacin caused gastric mucosal injury in the form of haemorrhages, increased the lipid peroxidation and decreased the levels of the antioxidant defense enzymes. Melatonin (20 mg/kg) and beta-carotene decreased the ulcer index and lipid peroxidation, and reduced the decrease in antioxidant enzyme levels. These findings suggest the melatonin and beta-carotene show protective effect against indomethacin induced gastric injury and this effect is mediated by scavenging of oxygen derived free radicals.     

L-carnitine inhibits ethanol-induced gastric mucosal injury in rats

L-carnitine is a quaternary amine that is essential for the normal oxidation of long-chain fatty acids by mitochondria. It is known that L-carnitine and its derivatives prevent the formation of reactive oxygen species, scavenge free radicals and protect cells from peroxidative stress. Oxygen-derived free radicals and lipid peroxidation products play a critical role in the pathogenesis of ethanol-induced gastric mucosal injury. The aim of the present study was to determine the effect of L-carnitine on lipid peroxidation induced by ethanol in the rat stomach. In our study, gastric mucosal injury was induced by the intragastric administration of 1 ml of absolute ethanol. Test compounds were given to rats by gavage 30 min before the ethanol administration. The animals were killed 60 min after the administration of ethanol. The stomach of each animal was removed. Mucosal damage was evaluated by macroscopic examination, histological analysis and by measurement of lipid peroxidation and glutathione activity. The intragastric administration of ethanol induced hyperemia and hemorrhagic erosions in the rat stomachs. L-carnitine significantly prevented gastric ulcerogenesis induced by ethanol and decreased the ulcer index. Plasma and gastric lipid peroxidation that was increased significantly by ethanol was decreased after treatment with L-carnitine. Ethanol treatment decreased significantly the gastric glutathione levels, and pretreatment with L-carnitine increased them significantly. Based on these data, the beneficial effects of L-carnitine on ethanol-induced gastric mucosal injury may be attributed to its antiperoxidative effects.     

Effect of nitric oxide synthase inhibition on the gastric mucosal barrier in rats.

The aim of this study was to investigate the effect of N-G-nitro-L-arginine-methyl ester (L-NAME), a nitric oxide synthase inhibitor, on the gastric mucosal barrier in rats. A group of Swiss albino rats received L-NAME (60 mg/kg/d) in their drinking water daily for 21 d. The mucin and prostaglandin E2 (PGE2) contents of the gastric mucosa were measured in gastric tissue samples. L-NAME intake did not affect gastric mucin, but it significantly reduced PGE2, a component of the gastric mucosal barrier. The results of this study imply that nitric oxide plays an important mediatory role in maintaining the gastric mucosal barrier. The inhibition of nitric oxide may be involved in the increased vulnerability of the gastric mucosa to injurious stimuli in rats.     

Role of antioxidants in gastric mucosal damage induced by indomethacin in rats

Reactive oxygen species play a role in the formation of gastric lesions induced by nonsteroidal antiinflammatory drugs. The present study was undertaken to determine whether endogenous antioxidants in gastric mucosa can protect it against the damaging effects of oxygen free radicals. This study examine oxygen free radical production (superoxide anions and hydrogen peroxide), gastric mucosa antioxidant defense mechanisms (glutathione, catalase, superoxide dismutase), the lesion-inducing effects of the generated oxygen free radicals (vascular permeability, lipid peroxidation) and gastric ulceration in rats treated orally with indomethacin at 10 mg/kg at 2 and 6 h after drug administration. Two hours after administration of the antiinflammatory drug, there was a sharp increase in production of oxygen free radicals in the gastric mucosa with no alteration in other parameters examined. Six hours after indomethacin administration the production of oxygen free radicals returned to basal levels, but there was a high degree of gastric ulceration and a significant increase in lipid peroxidation and vascular permeability together with decreases of 45% in glutathione concentration and 30% in catalase relative to the control group. These results suggest that like plasma, the gastric mucosa has an antioxidant capacity and only when this capacity is exhausted are the lesive effects of the oxygen free radicals manifested.     

化生平合剂对幽门结扎型大鼠胃黏膜损伤的保护作用

目的研究化生平合剂对幽门结扎型胃溃疡大鼠胃液分泌、胃泌素(GAS)和白介素-8(IL-8)的影响及对胃黏膜损伤的修复作用。方法将50只雄性SD大鼠随机分为模型组、化生平合剂高、中、低剂量组和阳性对照组,各组大鼠给药1周后用幽门结扎法进行造模,5h后观察大鼠胃液分泌及胃组织溃疡情况,分离血清,用放射免疫法测定GAS及IL-8的含量。结果化生平合剂高、中、低剂量组均能减轻幽门结扎型大鼠的胃黏膜损伤程度。与模型组相比,大鼠胃液量、胃酸排出量、血清GAS及IL-8的水平均有所降低。结论化生平合剂对幽门结扎型大鼠胃黏膜损伤具有保护修复作用,其机制与其降低胃酸排出量及抑制胃黏膜损伤因子有关。     

Efficacy of brown seaweed hot water extract against hcl-ethanol induced gastric mucosal injury in rats

Effect of pre-treatment with hot water extract of marine brown alga Sargassum polycystum C.Ag. (100 mg/kg body wt, orally for period of 15 days) on HCl-ethanol (150 mM of HCl-ethanol mixture containing 0.15 N HCl in 70% v/v ethanol given orally) induced gastric mucosal injury in rats was examined with respect to lipid peroxides, antioxidant enzyme status, acid/pepsin and glycoproteins in the gastric mucosa. The levels of lipid peroxides of gastric mucosa and volume, acidity of the gastric juice were increased with decreased levels of antioxidant enzymes and glycoproteins were observed in HCl-ethanol induced rats. The rats pre-treated with seaweed extract prior to HCl-ethanol induction reversed the depleted levels of antioxidant enzymes and reduced the elevated levels of lipid peroxides when compared with HCl-ethanol induced rats. The levels of glycoproteins and alterations in the gastric juice were also maintained at near normal levels in rats pre-treated with seaweed extract. The rats given seaweed extract alone did not show any toxicity, which was confirmed by histopathological studies. These results suggest that the seaweed extract contains some anti-ulcer agents, which may maintain the volume/acidity of gastric juice and improve the gastric mucosa antioxidant defense system against HCl-ethanol induced gastric mucosal injury in rats.     

Plaunotol prevents indomethacin-induced gastric mucosal injury in rats by inhibiting neutrophil activation

BACKGROUND: Activated neutrophils play a critical role in indomethacin-induced gastric mucosal injury. AIM: To investigate the effect of plaunotol, an anti-ulcer agent, on neutrophil activation in vitro and its effect on gastric mucosal injury and gastric accumulation of neutrophils in rats given indomethacin. METHODS: Human monocytes and neutrophils were isolated from the peripheral blood of healthy volunteers. We examined the effect of plaunotol on neutrophil elastase release, production of O2-, intracellular calcium concentration and expression of adhesion molecules CD11b and CD18 in activated neutrophils in vitro. The effect of plaunotol on TNF-alpha production by monocytes stimulated with endotoxin also was investigated in vitro. The effect of plaunotol (100 mg/kg, p.o.) on gastric mucosal injury and neutrophil accumulation was investigated in male Wistar rats given indomethacin (30 mg/kg, p.o.). RESULTS: Plaunotol inhibited the fMLP-induced release of neutrophil elastase from activated neutrophils, as well as the opsonized zymosan-induced production of O2- by neutrophils. Plaunotol significantly inhibited increased levels of intracellular calcium, a second messenger of neutrophil activation, in vitro. The fMLP-induced increases in CD11b and CD18 expression were also inhibited by plaunotol in vitro. Plaunotol inhibited monocytic production of TNF-alpha, a potent activator of neutrophils. Both gastric mucosal injury and gastric neutrophil infiltration in rats given indomethacin were significantly inhibited by the oral administration of plaunotol. CONCLUSIONS: Plaunotol inhibits indomethacin-induced gastric mucosal injury, at least in part by inhibiting neutrophil activation.     

Mechanism of ebrotidine protection against gastric mucosal injury induced by ethanol.

1. The gastroprotective properties of a new H2-receptor antagonist, ebrotidine, against ethanol-induced mucosal injury was investigated. 2. Groups of rats, with and without indomethacin pretreatment, received intragastrically either a dose of ebrotidine or vehicle only, followed by ethanol given at various intervals up to 4 hr. The gastric mucosa, 30 min after the ethanol challenge, was then subjected to macroscopic and histologic examination, and physicochemical measurements. 3. Ebrotidine at doses of 50 mg and higher per kg body wt effectively prevented the alcohol-induced mucosal injury, even in the presence of indomethacin. The protective effect was demonstrable already at 30 min, reached maximum at 1 hr, and persisted up to 3 hr. 4. Physicochemical analyses established that ebrotidine elicited 30% increase in mucus gel dimension, caused 19-20% increase in glycolipids and phospholipids, and evoked 21% increase in sulfomucin and 18% in sialomucins. As a consequence, the mucus gel viscosity increased by 1.4-fold, H+ retardation capacity by 16%, and hydrophobicity by 65%. 5. The results demonstrate that ebrotidine is a unique H2-antagonist endowed with a remarkable mucosal strengthening capability.     

Effects of antidepressants on alcohol-induced gastric mucosal injury in rats

The purpose of the present report is to study the effects of antidepressants such as trimipramine, amitriptyline, maprotiline and mianserin on severe gastric mucosal lesions produced by ethanol in comparison with cimetidine (H2-antihistamine) and dexchlorepheniramine (H2-antihistamine). The percentage of macroscopic mucosal lesions caused by alcohol affects 15% of the mucosal area. But pretreated with cimetidine the affected area was 9.18%, with dexchlorepheniramine 5.01%, with trimipramine 14.46%, with amitripytline 7.94%, with maprotiline 3.8%, and with mianserin 4.07%. Microscopic evaluation reveals that ethanol produces destruction of glandular cells and injures medial and basal layers. All drugs used previously to ethanol produce a decrease of microscopical lesions. A direct relation was found between micro and macroscopical lesions in rats treated with maprotiline, mianserin and dexchlorepheniramine.     

壳聚糖对大鼠胃损伤时黏膜的保护作用

目的研究壳聚糖对大鼠急性损伤时胃黏膜的保护作用。方法采用幽门结扎法建立大鼠损伤模型,然后收集胃液、胃损伤指数计分及SP免疫组化法实验。结果与对照组比较,实验组黏膜损伤指数显著下降(P<0.001);胃内游离酸和总酸度显著降低(P<0.05);诱导型一氧化氮合酶(iNOS)表达显著升高(P<0.01)。结论壳聚糖处理可明显减轻大鼠幽门结扎所致的胃黏膜损伤,对胃黏膜具有很好的保护作用。     

吉法酯对阿司匹林致大鼠急性胃黏膜损伤的保护作用

目的:研究吉法酯等胃黏膜保护剂对阿司匹林致大鼠急性胃黏膜损伤的保护作用及其机制.方法:60只健康雄性Wistar大鼠随机分为6组:空白对照组、单纯损伤组、400mg·kg-1吉法酯保护组、80mg·kg-1枸橼酸铋钾保护组、0.1mg·kg-1米索前列醇保护组和0.5g·kg-1硫糖铝保护组;每组各10只.各保护组动物分别用相应的药物提前给予灌胃处理,然后用阿司匹林行腹腔注射致大鼠急性胃黏膜损伤,分别测定各组的胃黏膜溃疡指数、胃黏膜血流、胃黏膜氨基己糖含量等指标,并在显微镜下观察组织学变化,以评价损伤程度及预防保护效果.结果:各预防保护组与单纯损伤组比较,胃黏膜损伤指数明显下降(P<0.001),胃黏膜血流明显增加(P<0.001),胃黏膜氨基己糖含量亦明显增加(P<0.001).组织学切片亦显示各预防保护组的损伤程度及炎症反应均较单纯损伤组明显减轻.结论:吉法酯对阿司匹林所致大鼠急性胃黏膜损伤具有明显的预防保护作用,与枸橼酸铋钾和米索前列醇的保护作用相当,优于硫糖铝.     

双嘧达莫与其它药物合用的新用途

本文介绍了近几年来双嘧达莫与其它药物合用的新用途,表明双嘧达莫通过与其它药物合用拓展了其临床应用范围,并有增强疗效、减少不良反应等作用.     

Vitamin E: A potential therapy for gastric mucosal injury

Context: Many scientific reports have shown the involvement of oxidative stress and inflammation as well as diminished gastroprotective substances in the pathogenesis of gastric lesions using various models. Therefore, treatment with antioxidants like tocopherol and tocotrienol may afford beneficial effects in attentuating the formation of the gastric lesions.

Objective: The aim of this work was to summarize documented reports on the effects of vitamin E on various models of gastric lesion.

Methods: A literature search was performed from databases in Medline (PubMed), Web of Science, ScienceDirect, and Googlescholar from June to December 2013.

Results and conclusion: The potential roles of tocopherol and tocotrienol in modifying the effects of ulcerogenic agents are discussed in this review. The protective effects of the vitamin E might involve ameliorating oxidative stress and inflammation as well as restoration of endogenous gastroprotective substances. This vitamin has the potential to be used as a therapy for gastric mucosal injury.