Alcohol-induced Gastric Injury Research Articles

Protective effects of Lactiplantibacillus pentosus CQZC01 on alcohol-induced gastric mucosa injury in mice via an anti-oxidative mechanism

Protective effects of Lactiplantibacillus pentosus CQZC01 on alcohol-induced gastric mucosa injury in mice via an anti-oxidative mechanism

Gastroprotective Effects of Ganoderma lucidum Polysaccharides with Different Molecular Weights on Ethanol-Induced Acute Gastric Injury in Rats.

Ganoderma lucidum is known as a medicine food homology that can ameliorate gastrointestinal diseases. To evaluate the gastroprotective effects on different Ganoderma lucidum polysaccharides (GLPs), GLP was separated into three parts with different molecular weights using 100 kDa, 10 kDa, and 1 kDa membranes. The mitigation effects of different GLPs on ethanol-induced acute gastric injury were observed in rats. After pretreatment with different GLPs, especially GLP above 10 kDa, the symptoms of gastric mucosal congestion and bleeding were improved; serum myeloperoxidase, inflammatory factor, and histamine were decreased; and antioxidant activity and defense factors (NO and EGF) were increased. Results showed that GLP with different molecular weights had a dose-dependent effect in alleviating alcohol-induced gastric injury. The underlying mechanism might be related to regulating anti-oxidation, promoting the release of related defense factors, reducing inflammatory factors, and reducing the level of histamine in serum. The current work indicated that GLPs above 10 kDa could be applied as natural resources for producing new functional foods to prevent gastric injury induced by ethanol.

Gastric acid-response chitosan/alginate/tilapia collagen peptide composite hydrogel: Protection effects on alcohol-induced gastric mucosal injury

Long-term excessive alcohol intake can easily lead to gastritis, gastric ulcer, and gastric bleeding. In this paper, the gastric acid-responsive hydrogel of CS-NAC/alginate/tilapia collagen peptide (CS-NAC/ALG/TCP) was developed. Its structure and properties were determined. The alcohol-induced gastric mucosal injury models in mice were established to evaluate the protective effects of CS-NAC/ALG/TCP. The results showed that CS-NAC/ALG/TCP was successfully fabricated, and it showed a sustained release of TCP, strong mucoadhesion, and excellent biodegradability in vitro. In the animal experiments, CS-NAC/ALG/TCP improved the oxidative stress status of the gastric mucosa by increasing the levels of SOD, GSH, and CAT in tissues. It also down-regulated the expression of MPO, TNF-α, IL-1β, and IL-6, and increased the production of gastric protective factors such as PGE2 and NO in mouse stomach, thereby reducing the alcohol-induced inflammation and protecting the gastric mucosal injury. Besides, CS-NAC/ALG/TCP can also increase the activities of alcohol metabolism enzymes to improve alcohol metabolism, thereby reducing alcoholic damage. In conclusion, CS-NAC/ALG/TCP is a promising candidate for the treatment of alcohol-induced gastric injury.

Lactobacillus plantarum ZS62 Alleviates Alcohol-Induced Gastric Injury in Mice via an Anti-Oxidative Mechanism.

AimGastric mucosal injury is a typical characteristic of gastric diseases. The prevalence of gastric mucosal injury caused by alcohol has been on the rise, which has been considered a serious problem. The purpose of this study is to explore the protective effect on gastric injury of Lactobacillus plantarum ZS62 (LP-ZS62) isolated from naturally fermented yak yoghurt.MethodsWe established a gastric injury model through alcohol and evaluated the protective effect of LP-ZS62 on gastric injury in mice. The injury to the gastric mucosa, histopathological sections, related biochemical indicators, and related genes were examined to evaluate the protective effect of LP-ZS62.ResultsLP-ZS62 effectively alleviated alcohol-induced gastric injury according to visual observations of gastric tissue and pathological tissue sections. The experimental results revealed that LP-ZS62 decreased malondialdehyde (MDA) level, and elevated superoxide dismutase (SOD) and glutathione (GSH) levels in gastric tissues. Additionally, LP-ZS62 increased glutathione peroxidase (GSH-Px), prostaglandin E2 (PGE2), and somatostatin (SS) levels. LP-ZS62 also decreased inflammatory cytokines interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and IL-6 levels, and increased the anti-inflammatory cytokine IL-10 level. The quantitative polymerase chain reaction results showed that LP-ZS62 upregulated mRNA expression of nuclear factor E2-related factor 2 (Nrf2), copper/zinc superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), catalase (CAT), gamma-glutamylcysteine synthetase (GSH1), and glutathione peroxidase (GSH-Px).ConclusionThis study confirmed that LP-ZS62 alleviated alcohol-induced gastric injury by regulating antioxidant capacity. Therefore, LP-ZS62 could be developed as a probiotic product to treat alcoholic gastric injury.

Research progress on anti-alcoholic gastric injury active components and mechanisms of Chinese herbal medicine

Alcohol is considered to be one of the main causes for gastric injury, and alcoholic gastric injury has been becoming one of the global health problems, which seriously affects the quality of human life. Many studies suggest that the active components extracted from Chinese herbal medicine can effectively reduce the degree of alcohol-induced gastric injury. The active components and its mechanism of anti-alcoholic gastric injury of Chinese herbal medicine reported in recent five years were preliminarily summarized according to the classification of terpenoids, flavonoids, polyphenols, polysaccharides, volatile oils, phenylpropanoids and alkaloids in this paper. The terpenoids could improve oxidative stress and inflammatory response by regulating relevant signaling pathways. The flavonoids are mainly related to antioxidant and anti-inflammatory properties. The polyphenols mainly regulate the level of relevant factors involved in inflammatory pathway, oxidative stress and apoptosis pathway. The polysaccharides could enhance the ability of gastric mucosal defense factor by inhibiting oxidative stress injury and inflammatory response. Phenylpropanoids could enhance the gastric mucosal defense factor. The volatile oils mainly inhibit H~+/K~+-ATPase activity or inflammatory reaction. Alkaloids are closely related to the inhibition of inflammatory response and the improvement of antioxidant system. This paper aims to provide reference for further research and development of Chinese herbal medicine against alcoholic gastric injury.

Inhibitory Effect of Flavonoid Extract of Lotus Leaf on Alcohol-Induced Gastric Injury by Antioxidant Capacity in Mice

The aim of this study was to investigate the antioxidant effects of flavonoid extract of lotus leaf (FELL) in vitro and in mice with gastric injury and elucidate the inhibitory effect of FELL on alcohol-induced gastric injury by antioxidant capacity. Gastric juice volume and acid value were measured in the established alcohol-induced acute gastric injury model in mice. Hematoxylin and eosin staining demonstrated the morphological changes in the gastric mucosa. FELL improved the alcohol-induced gastric lesions. Serological testing results showed that FELL significantly increased the levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and nitric oxide (NO) and significantly reduced the levels of MDA and MPO in mice with gastric injury. Besides, FELL significantly reduced the levels of interleukin 6 (IL-6), interleukin 12 (IL-12), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ). The quantitative polymerase chain reaction (qPCR) and Western blot results proved that FELL upregulated the mRNA and protein expressions of SOD1, SOD2, CAT, epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), neuronal nitric oxide synthase (nNOS), and endothelial nitric oxide synthase (eNOS) and downregulated the expression of inducible nitric oxide synthase (iNOS) in the gastric tissue of mice with gastric injury. Five compounds, including kaempferitrin, hyperoside, astragalin, phloridzin, and quercetin, were detected in FELL using high-performance liquid chromatography. Thus, FELL has an inhibitory effect on experimental alcohol-induced gastric injury because of the antioxidant capacity of the five compounds. Its effect increases as the FELL concentration increases, which is close to that of ranitidine. FELL, which is an active substance, provides a good gastroprotective effect.

Wu Shan Shen Cha (Malus asiatica Nakai. Leaves)-Derived Flavonoids Alleviate Alcohol-Induced Gastric Injury in Mice via an Anti-Oxidative Mechanism.

Wu Shan Shen Cha is the leaf of Malus asiatica Nakai., a special type of tea that is consumed in the same way as green tea. To study the effect of Wu Shan Shen Cha-derived flavonoids (WSSCF) on lesions in the stomach, a 15% hydrochloric acid–95% ethanol (volume ratio 4:6) solution was used to induce gastric injury in mice. The degree of gastric injury was assessed using tissue specimens, and the effects of WSSCF on the serum levels of antioxidant enzymes were investigated. The results showed that WSSCF could alleviate the damage of the gastric mucosa and gastric wall caused by the hydrochloric acid–ethanol solution, decrease the tissue and serum levels of malondialdehyde (MDA) in mice with gastric injury, and increase the serum levels of superoxide dismutase (SOD) and glutathione (GSH). The results of quantitative polymerase chain reaction (qPCR) showed that WSSCF could increase the mRNA expression of Mn-SOD, Cu/Zn-SOD, catalase (CAT), endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) in tissue specimens from mice with gastric injury and decrease the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). At the same time, the results of the high concentration of WSSCF (WSSCFH) group were closer to those of the drug (ranitidine) treatment group. Wu Shan Shen Cha-derived flavonoids had a good antioxidant effect, so as to play a preventive role in alcoholic gastric injury.

Preventive Effect of Anji White Tea Flavonoids on Alcohol-Induced Gastric Injury through Their Antioxidant Effects in Kunming Mice.

Anji white tea (Camellia sinensis) is a traditional Chinese tea beverage, which is classified as green tea and contains an abundant amount of flavonoids. In this study, the preventive effect of Anji white tea flavonoids (AJWTFs) on ethanol/hydrochloric acid-induced gastric injury in mice was evaluated. The serum and gastric tissues of mice were analyzed using a biochemical kit and by quantitative polymerase chain reaction (qPCR). Observation of the appearance of the stomach indicated that AJWTFs could effectively reduce the area of gastric injury caused by ethanol/hydrochloric acid, and the inhibition rate of AJWTF on gastric injury increased with an increase in AJWTF concentration. The Anji white tea flavonoids could also reduce the volume and pH of gastric juice in mice with gastric injury. Biochemical results showed that AJWTFs could increase the superoxide dismutase (SOD) and glutathione (GSH) activities, as well as decrease the malondialdehyde (MDA) level, in the serum and liver of mice with gastric injury. Pathological observation confirmed that AJWTFs could inhibit the tissue damage caused by ethanol/hydrochloric acid in the stomach of mice. Further qPCR experiments also showed that AJWTFs could inhibit the decreases in neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), copper/zinc superoxide dismutase (Cu/Zn–SOD), manganese superoxide dismutase (Mn–SOD), catalase (CAT), and the increase in inducible nitric oxide synthase (iNOS) expression in the gastric tissue of mice caused by gastric injury. As observed, AJWTFs exerted a good preventive effect on alcohol-induced gastric injury in mice induced by ethanol/hydrochloric acid, and the effect is close to that of ranitidine. Anji white tea flavonoids present good antioxidant effect, which allows them to effectively prevent alcoholic gastric injury and be used as biologically active substances with a broad range of applications.

Novokinin inhibits gastric acid secretion and protects against alcohol-induced gastric injury in rats.

Novokinin (Arg-Pro-Leu-Lys-Pro-Trp), a potent vasorelaxing and hypotensive peptide modified from ovokinin, exhibits highly selective affinity for the AT2 receptor. However, its role in gastrointestinal functions is still not fully understood. In this study, we found that novokinin inhibited basal gastric acid secretion and protected gastric mucosa from alcohol-induced injury in a dose-related manner in rats after intracerebroventricular (i.c.v.) administration. Novokinin significantly decreased basal gastric acid output at the dose of 50 and 100nmol/rat. The effect of novokinin on gastric acid secretion was reversed by central injection of PD 123319 (10nmol/rat), an AT2 receptor antagonist, and peripheral injection of indomethacin (10mg/kg), an inhibitor of prostaglandin synthesis. Meanwhile, pre-treatment with novokinin at doses of 10, 50, and 100nmol/rat significantly reduced the alcohol-induced gastric mucosal injury compared to the ulcer-control group, which was inhibited by indomethacin (10mg/kg). The result showed a remarkable increase in the level of prostaglandin E2 (PGE2), glutathione (GSH), and a decrease in malondialdehyde (MDA) after i.c.v. administration of novokinin. These findings suggest that the inhibitory effect of novokinin on gastric acid secretion is probably mediated via an AT2 receptor-prostaglandins (PGs) pathway. The gastroprotective effect of novokinin might be attributed to the inhibition of acid secretion, the cytoprotection of PGs, and the antioxidant property.

Protective effect of Bojungikki-tang, a traditional herbal formula, against alcohol-induced gastric injury in rats

Ethnopharmacological evidenceOxidative stress plays an important role in the pathogenesis of ethanol-induced acute gastric mucosal injury. Bojungikki-tang (Hochuekkito in Japanese, Bu-zhong-yi-qi-tang in Chinese) is a traditional herbal formula used in Korea, Japan, and China to treat allergic diseases and gastrointestinal disorders. However, the mechanism responsible for its actions has not been investigated experimentally. Aim of the studyThe aims of this study were to investigate whether Bojungikki-tang water extract (BJITE) has protective effects against ethanol-induced acute gastric injury in rats and to perform an acute toxicity study to evaluate its safety. Materials and methodsIn this rat model, gastric mucosal injury was imposed by oral administration of 5mL/kg body weight of absolute ethanol. BJITE at one of two doses (200 or 400mg/kg body weight) was administered by gavage 2h before ethanol administration. Gastric tissues were collected and analyzed to assess the gastric injury index, and content or activity of catalase, superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), glutathione-S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPx). ResultsAcute administration of ethanol significantly increased the gastric injury index concomitantly with an increase in MDA and GSH content, and a decrease in the activities of catalase, GST, GR, GPx, and SOD. Pretreatment with 200 or 400mg/kg BJITE attenuated ethanol-induced gastric mucosal injury; this was accompanied by an increase in the content or activity of PGE2, catalase, GSH, GST, GR, GPx, and SOD, and a decrease in MDA content. In the acute toxicity study, no adverse effects of BJITE were observed at doses up to 2000mg/kg body weight. ConclusionThese results indicate that BJITE can partly protect the gastric mucosa from ethanol-induced acute gastric injury and suggest that these protective effects might be induced by increasing the antioxidant status. We suggest that BJITE can be developed as an effective drug for the treatment of acute gastric injury.

Protective effect of sericin peptide against alcohol-induced gastric injury in mice

Sericin peptide (SP) has shown a powerful anti-oxidant property in a host of studies. The present study was designed to investigate the possible protective effects of SP against alcohol-induced gastric lesions in mice and to explore the potential mechanisms. Animals were randomly divided into 5 groups: control, alcohol (56%, 14.2 ml/kg), SP-treated mice (0.2, 0.4, 0.8 g/kg). Mice were pretreated with SP before administering alcohol, the concentration of ethanol in serum and urine, the contents of malondialdehyde (MDA), glutathione (GSH) and the glutathione peroxidase (GSH-PX), catalase (CAT) and superoxide dismutase (SOD) activities in the gastric mucosa were measured, subsequently, the pathological evaluation of stomach was also observed. Of the animals pre-treated with SP (0.4, 0.8 g/kg), the concentration of ethanol in serum was significantly decreased, while increased in urine as compared to the alcohol-administered alone animals. Alcohol administration caused severe gastric damage as indicated by markedly increased MDA levels and decreased antioxidants, such as reduced GSH, GSH-PX and SOD in the gastric tissue while the CAT activity was not altered. On SP administration there was a reversal in these values towards normal. Histopathological studies confirmed the beneficial role of SP, which was in accordance with the biochemical parameters. SP could protect gastric mucosa from alcohol-induced mucosal injury. These gastroprotective effects might be due to increasing 'first-pass metabolism' in the stomach and hastening ethanol elimination directly through the urine. SP might also play an important role in the protection of the structure and function of gastric mitochondria, at least partly based on their anti-oxidant effect.

Lactic acid bacteria prevent alcohol-induced steatohepatitis in rats by acting on the pathways of alcohol metabolism

The objective is to study the possible mechanism by which lactic acid bacteria (LAB) prevent alcohol-induced steatohepatitis in rats. A total of 25 Wistar rats were divided into three groups: a LAB-fed group, an alcohol-treated group and a control group. Both the LAB-fed group and the alcohol-treated group received alcohol (10 g kg(-1) per day) orally for up to 5 days (125 h). Before exposure to alcohol, the LAB-fed group were first treated daily with 1.5 ml/100 g of a mixture comprising 4 x 10(10) ml(-1) of Lactobacillus acidophilus and 2.5 x 10(7) ml(-1) of Bifidobacterium longum, while the control group was treated with normal saline only. Biochemical data, alcohol dehydrogenase (ADH) activity and histology of the liver and stomach were evaluated. The ADH activity in the LAB mixture was 3.52 +/- 0.45 mumol mg(-1) protein (10(9) CFU ml(-1)), and was dose-dependent. By 30 min after taking alcohol, serum alcohol concentrations were 514.24 +/- 80.21 microg ml(-1) in the LAB-fed group and 795.15 +/- 203.45 microg ml(-1) in the alcohol-treated group (P < 0.005). Serum alcohol concentrations were reduced by 48% (P < 0.01) in the LAB-fed group, but by only 4% in the alcohol-treated group (P > 0.05) 120 min after oral intake of alcohol. The blood levels of endotoxin, AST and ALT were improved in the LAB-fed group compared to the alcohol-fed group (P < 0.01). All alcohol-treated rats showed moderate to severe steatohepatitis, but the LAB-fed rats showed almost normal histology or very slight lesions only. In conclusion, LAB decreased the alcohol concentration in the blood by increasing the first-pass metabolism in both the stomach and the liver, and effectively protected against alcohol-induced gastric and liver injury. It is interesting to note that the protection was more effective in the liver.

The effect of polysaccharide extracted from the marine alga Capsosiphon fulvescens on ethanol administration

Seaweed extracts have recently been found to have antioxidant and antitumor activities . Capsosiphon fulvescens ( Cf) is a green alga and nutrient-dense food source. In a previous study, we extracted polysaccharide from Cf ( Cf–PS) and demonstrated its antitumor effect in gastric cancer cells. In this report, we describe the protective effect of Cf–PS against alcohol-induced gastric injury in rats and adenocarcinoma (AGS) cells. In vivo assay revealed stomach damage in rats treated with alcohol alone; however, the stomach condition of rats co-treated with Cf–PS and alcohol matched that of the control group. Cf–PS also inhibited alcohol-induced cell death in AGS cells. Compared with alcohol treatment alone, Cf–PS and alcohol co-treatment increased phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt but inhibited poly-ADP-ribose polymerase (PARP) cleavage. Thus, ERK1/2 and Akt activation are instrumental in the protective effect of Cf–PS against alcohol-induced cell death in AGS cells. Moreover, Cf–PS treatment reduced the expressions of cyclooxygenase-2 (COX-2) and the inducible form of nitric oxide ( iNOS), proteins related to ulcers. These results suggest that Cf–PS could help protect against alcohol-induced peptic ulcers.

Transgenic Mini-tomato and Protection Against Alcohol-induced Gastric Injury

The epidermal growth factor (EGF) has been shown to promote the proliferation of various types of cells, to maintain the physiological function of the mucosa of the digestive tract, and to promote the healing of the gastric and duodenal ulcers. It has been expressed in many types of bacteria and yeasts. In this article, a bio-reactor was constructed, namely, the human EGF (hEGF) transgenic mini-tomato. On the basis of hEGF gene sequence, a tomato codon preference hEGF gene was chemically synthesized, and it was constructed into the plant expression vector pCAMBIA2300. The transgenic tomato plants containing gene hEGF were obtained through Agrobacterium-mediated transformation. The expression product was determined by radioimmunoassay (RIA) and showed a yield of 3.48 ± 1.01 ng/g fresh fruits. The intragastric gavage (ig) administration of the rhEGF–containing juice of the transgenic tomato (equivalent to 24 ng rhEGF per mouse a day) for 15 days could significantly protect mice against the alcohol-induced ulceration. The ulcer index, expressed as a degree of the stomach lesion, decreased from 42.20 ± 18.13 to 16.25 ± 9.57.

Protective action of gastrin-17 against alcohol-induced gastric injury in the rat: role in mucosal defense.

Exogenous cholecystokinin (CCK) or exposure of the stomach to the mild irritant 25% ethanol can prevent gastric injury. Ingestion of ethanol also elicits the release of CCK as well as gastrin, which is structurally similar to CCK. This study was undertaken in conscious rats to examine the gastroprotective actions of gastrin and to assess the effect of CCK-gastrin receptor blockade on adaptive cytoprotection with ethanol as the mild irritant. Intravenous (1-25 pmol/kg) administration of gastrin-17 dose dependently increased gastric mucosal blood flow (laser Doppler) and reduced gastric injury caused by 1 ml of orally administered acidified ethanol (150 mM HCl-50% ethanol). Similar gastroprotection was achieved with the gastrin secretagogue 5% peptone (1 ml orogastrically). The gastroprotective capabilities of gastrin-17 were attenuated by the type B CCK (gastrin) receptor antagonist L-365,260 (12.5-25 mg/kg i.p.) and by capsaicin desensitization (125 mg/kg s.c.). CCK octapeptide (5 nmol/kg i.v.)-induced protection was reversed by the type A CCK receptor antagonist MK-329 (1 mg/kg i.p.). Neither receptor antagonist, alone or in combination, reversed the protective effects of the mild irritant 25% ethanol (1 ml orogastrically). Thus, whereas gastrin may play a role in gastric mucosal defense, neither CCK nor gastrin appears to participate in the phenomenon of adaptive cytoprotection.

Cholecystokinin is a potent protective agent against alcohol-induced gastric injury in the rat. Role of endogenous prostaglandins.

Cholecystokinin is a gastrointestinal hormone known to physiologically regulate pancreatic protein secretion and gallbladder contractility. Some evidence suggests that cholecystokinin is also involved in the maintenance of gastrointestinal mucosal integrity. This study was undertaken to ascertain whether cholecystokinin could prevent the gastric mucosal injury induced by acidified ethanol and what role prostaglandins, and type A and type B cholecystokinin receptors might play in this process. Conscious, fasted rats were given subcutaneous saline or cholecystokinin octapeptide (10-100 micrograms/kg) 30 min before a 1-ml oral gastric bolus of acidified ethanol (150 mM HCl/50% ethanol). Five minutes later, rats were sacrificed and the total area of macroscopic injury quantitated (square millimeters). In additional experiments using a similar protocol, 1 ml of either the cyclooxygenase inhibitor, indomethacin (5 mg/kg), a type A cholecystokinin receptor antagonist, L-364,718 (0.01-1 mg/kg), or the type B cholecystokinin receptor antagonist, L-365,260 (12.5-25 mg/kg) was given intraperitoneally 30 min prior to pretreatment with cholecystokinin octapeptide. Cholecystokinin octapeptide dose-dependently prevented mucosal injury from acidified ethanol (corroborated by histology). The protective effect of cholecystokinin octapeptide was completely negated by L-364,718 and partially reversed by indomethacin, while L-365,260 had no discernible effect in this process. In a further study, cholecystokinin was unable to prevent the damaging effects of aspirin and the inhibition of endogenous prostaglandins. This, it appears that cholecystokinin is able to maintain mucosal integrity in the face of a damaging insult by activation of type A cholecystokinin receptors, an effect mediated, at least in part, through the release of endogenous prostaglandins.

Adverse effects of vagotomy on ethanol-induced gastric injury in the rat. Absence of a role for glutathione redox cycle.

Truncal vagotomy is known to aggravate the damaging effects of alcohol-induced gastric injury and prevent the occurrence of adaptive cytoprotection against such injury by a mild irritant. This study was undertaken to determine whether aberrations in glutathione (GSH) metabolism were responsible for these vagotomy-induced effects. Fasted rats (6-8/group) were subjected to truncal vagotomy and pyloroplasty or sham vagotomy and pyloroplasty. One week later they were given 2 ml of oral saline or the mild irritant, 25% ethanol (EtOH). Thirty minutes following such treatment, animals were either sacrificed or orally received 2 ml of 100% EtOH and then were sacrificed 5 min later. At sacrifice, in each experimental group, stomachs were removed and either evaluated macroscopically for the degree of injury involving the glandular gastric epithelium or samples of the mucosa were prepared for measurement of total GSH levels or GSH peroxidase (GPX) and GSH reductase (GRT) activity. In nonvagotomized animals, saline treatment prior to 100% EtOH exposure resulted in injury to the glandular epithelium involving approximately 18%. Treatment with 25% EtOH prior to 100% EtOH exposure virtually abolished this injury. In vagotomized animals, 100% EtOH elicited almost three times the amount of injury observed in the nonvagotomized state and the protective effect of 25% EtOH pretreatment was prevented. Effects of the various treatment modalities on GPX and GRT activity were not significantly different from control values. When mucosal GSH results were plotted against the presence or absence of gastric injury among the various groups studied, no significant correlation was apparent.(ABSTRACT TRUNCATED AT 250 WORDS)

Protection against ethanol injury in the canine stomach: role of mucosal glutathione

The present study determined the role that mucosal glutathione (GSH) levels play in mediating the protective effects of a prostaglandin and a mild irritant against alcohol-induced gastric injury. An in vivo canine chambered stomach preparation was used in which the exteriorized mucosa was partitioned into two equal halves, one serving as control. Animals (5-8/group) received a subcutaneous injection of either normal saline (NS) or the GSH depletor N-ethylmaleimide (NEM; 50 mg/kg) and then were assigned to one of a variety of groups based on the perfusate used to bathe the experimental side of the chamber; NS bathed the control mucosa. At completion of the studies, mucosa from each side of the chamber was assayed for total GSH (mumol/g wet wt) and evaluated for microscopic damage. Both 16,16-dimethyl prostaglandin E2 (PGE2) (1 microgram/ml) and the mild irritant 8% ethanol, when topically applied to the gastric epithelium, increased mucosal GSH levels by approximately 20% compared with control values, and elicited no deleterious effects to the mucosa. Treatment of animals with NEM prevented these GSH effects by PGE2 and 8% ethanol without damaging the mucosa. Application of 40% ethanol to the mucosa markedly reduced levels of GSH and caused significant injury to the mucosal surface, much of it extending to the level of the gastric glands. When mucosa was pretreated with PGE2 or 8% ethanol before 40% ethanol exposure, deep gastric gland injury was virtually abolished. In animals receiving NEM, the protective effects of these agents against injury by 40% ethanol were prevented. Perturbations in tissue levels of GSH under these various experimental conditions failed to correlate histologically with the status of gastric mucosal integrity.

Effect of ethanol-generated free radicals on gastric intrinsic factor and glutathione

The oxidation of acetaldehyde (generated from the metabolism of ethanol) by oxidases such as xanthine oxidase generates free radicals which can mobilize ferritin iron, alter hepatic glutathione and produce lipid peroxidation. The stomach, a site of ethanol metabolism and rich in xanthine oxidase, was studied with respect to the effects of ethanol on intrinsic factor (IF) binding of vitamin B-12 as well as gastric glutathione (GSH). Incubations of gastric homogenates with acetaldehyde-xanthine oxidase inhibited the B-12 binding ability by IF. A large acute dose of ethanol in vivo (5 g/kg, conc. >40% w/v) decreased gastric IF binding of B-12 and depressed gastric GSH; these effects were markedly attenuated by the feeding of sodium tungstate which inhibited xanthine oxidase. Changes in B-12 binding paralleled changes in gastric GSH. Scatchard plots of IF binding of B-12 for homogenates suggested decreased number of binding sites rather than altered affinity. In conclusion, the gastric metabolism of ethanol generates free radicals which alter IF binding of B-12, depress gastric GSH and may play a role in alcohol-induced gastric injury.

Influence of vagotomy on mucosal protection against alcohol-induced gastric damage in the rat

We examined the role of the vagus nerve in mediating the protective effects of subcutaneous 16,16-dimethyl prostaglandin E2 (16,16-dmPGE2) or of the mild irritant 30% ethanol (topically) against gastric mucosal injury induced by concentrated solutions of ethanol. Anesthetized rats underwent either truncal vagotomy or sham truncal vagotomy and were studied acutely or 7 days later. Under acute conditions, in rats with intact vagi, oral saline followed by 100% ethanol produced severe gastric hemorrhagic and necrotic lesions throughout the glandular gastric mucosa. Oral 30% ethanol or pretreatment with 16,16-dmPGE2 (5, 10, or 25 μg/kg) before giving oral saline significantly reduced the magnitude of injury when mucosa was subsequently exposed to 100% ethanol. In animals with truncal vagotomy, the protective effect of 16,16-dmPGE2 or 30% ethanol was not observed. Similar results were noted when animals were studied 7 days after sham or truncal vagotomy. In other studies, the ability of 16,16-dmPGE2 to prevent gastric injury induced by 50% ethanol or 80 mM aspirin in acid solution (160 mM HCl) with and without prior vagotomy was compared. Although 16,16-dmPGE2 (5 or 25 μg/kg) pretreatment significantly reduced the degree of gastric damage induced by both agents in the nonvagotomized state, and by aspirin under vagotomized conditions, only partial protection by 16,16-dmPGE2 against ethanol injury was observed in the vagotomized state. These results suggest that the mechanisms whereby prostaglandins mediate their protective effects against aspirin and ethanol may be different and that the vagus nerve influences the ability of 16,16-dmPGE2 and of the mild irritant 30% ethanol to prevent alcohol-induced gastric injury in the rat stomach.