Gastric Lipid Peroxidation Research Articles

Regular moderate exercise alleviates gastric oxidative damage in rats via the contribution of oxytocin receptors.

A moderate level of exercise has beneficial effects for the prevention of gastric ulcers. Although regular aerobic exercise was shown to elevate serum oxytocin levels and exogenously administered oxytocin exerts an anti-ulcer activity, the role of endogenous oxytocin in the gastroprotective effects of exercise has not yet been elucidated. We showed that increased anxiety and oxidative gastric damage induced by gastric ulcers were reversed in pre-exercised rats, while reduced hypothalamic oxytocin expression and decreased myenteric oxytocin receptor expression due to gastric ulcers were abolished by exercise. We also reported that the blockade of oxytocin receptors exaggerated gastric damage in exercised rats with ulcers. Our data establish that endogenous oxytocin is the key mediator in the beneficial effects of regular physical activity in alleviating gastric injury. Exercise increases serum oxytocin levels and exogenous oxytocin exerts an anti-ulcer activity; but the role of oxytocin in the protective effects of exercise against gastric ulcers has not yet been evaluated. This study was designed to investigate the impact of regular swimming exercise on oxidative gastric injury, and the role of oxytocin receptor activity in the anxiolytic and anti-inflammatory actions of exercise. Adult Wistar albino rats of both sexes performed swimming exercise (30min/day, 5days) or stayed sedentary. At the end of the 6-week exercise/sedentary protocol, rats were injected intraperitoneally with atosiban (0.1mg/kg/day) or saline for 4days. On the 5th day, under anaesthesia, acetic acid (ulcer) or saline (sham) was applied onto the gastric serosa and the treatments were continued. On the 9th day, anxiety levels were determined; gastric blood flow was measured, and blood, gastric and brain tissues were obtained. Induction of ulcers in sedentary rats increased anxiety and serum corticosterone levels; but reduced gastric blood flow and resulted in apoptosis and oxidative gastric damage with increased cytokine expressions. However, when ulcers were induced in pre-exercised rats, behavioural and biochemical alterations due to gastric damage were reversed. The inhibition of oxytocin receptors by atosiban exaggerated pro-inflammatory cytokine expressions and gastric lipid peroxidation in the stomachs of exercised rats with ulcers. When rats had regularly exercised prior to ulcer induction, reductions in the immunolabelling of hypothalamic oxytocin and myenteric oxytocin receptors were abolished, suggesting that exercise-induced alleviation of gastric injury may involve the reversal of down-regulated oxytocinergic activity.

EVALUATION OF ANTIPYRETIC AND ANTIULCER ACTIVITY OF ETHANOLIC EXTRACT OF LEAVES OF TREMA ORIENTALIS L. IN ALBINO WISTAR RATS

Objectives: The purpose of the present study was aimed at evaluating the antipyretic and antiulcer activity on leaves of Trema orientalis L. (family Cannabaceae) on albino Wistar rats. The antipyretic and antiulcer activity of the ethanolic extract of the T. orientalis L. leaves in three different concentrations (100, 200, and 300 mg/kg) was compared with standard paracetamol and pantoprazole, which was evaluated by employing Brewer’s yeast-induced pyrexia and ethanol-induced ulcer model. The biochemical parameters such as the volume of gastric juice secretion, pH, total acidity, ulcer index, percentage protection, and lipid peroxidation were also studied.
 Methods: T. orientalis leaves were extracted with ethanol by the Soxhlet extraction method. The dried extract was used for further phytochemical and pharmacological analysis. The antipyretic effect was studied using Brewer’s yeast-induced pyrexia. The ethanol-induced ulcer model was used to study the antiulcer effect.
 Results: The percentage yield of ethanolic extract of T. orientalis leaves was found to be 6.71% w/w, respectively. The extract showed significant antipyretic and antiulcer effect when compared with standard paracetamol and pantoprazole.
 Conclusion: The ethanolic extract of T. orientalis has significant antipyretic and antiulcer action.

EVALUATION OF ANTIPYRETIC AND ANTIULCER ACTIVITY OF ETHANOLIC EXTRACT OF LEAVES OF ALSTONIA SCHOLARIS L. IN ALBINO WISTAR RATS

Objective: The purpose of the present study was aimed at evaluating the antipyretic and antiulcer activity on leaves of Alstonia scholaris L. (Family Apocynaceae) on albino Wistar rats. The antipyretic and antiulcer activity of the ethanolic extract of the A. scholaris L. leaves in three different concentrations (50, 100, and 200 mg/kg) were compared with standard paracetamol and pantoprazole, which was evaluated by employing brewer’s yeast-induced pyrexia and ethanol-induced ulcer model. The biochemical parameters such as the volume of gastric juice secretion, pH, total acidity, ulcer index, percentage protection, and lipid peroxidation (LPO) were also studied.
 Methods: A. scholaris leaves were extracted with ethanol by Soxhlet extraction method. The dried extract was used for further phytochemical and pharmacological analysis. The antipyretic effect was studied using brewer’s yeast-induced pyrexia. The ethanol-induced ulcer model was used to study the antiulcer effect.
 Results: The percentage yield of ethanolic extract of A. scholaris leaves was 15.81%w/w, respectively. The extract showed significant antipyretic and antiulcer effects when compared with standard paracetamol and pantoprazole.
 Conclusion: The ethanolic extract of A. scholaris has significant antipyretic and antiulcer activity.

Protective effects of a triple-fermented barley extract (FBe) against HCl/EtOH-induced gastric mucosa damage in mice.

This study was designed to observe the possible protective effects of a triple‐fermented barley (Hordeum vulgare L.) extract (FBe) obtained by saccharification and using Saccharomyces cerevisiae and Weissella cibaria in alleviating gastric damage induced by a hydrochloric acid (HCl) and ethanol (EtOH) mixture in mice. After oral administration of FBe (300, 200, and 100 mg/kg) followed by 1 hr before and after the single treatment of HCl/EtOH (H/E) mixture, the hemorrhagic lesion scores, histopathology of the stomach, gastric nitrate/nitrite content, lipid peroxidation, and antioxidant defense systems including catalase and superoxide dismutase activities were observed. Following a single oral treatment of H/E‐induced gastric damages as measured by hemorrhagic gross lesions and histopathological gastric, ulcerative lesions were significantly and dose‐dependently (p < 0.01 or p < 0.05) inhibited in mice, when all three different doses of FBe were administered as compared to those in H/E control mice. In particular, FBe also increased gastric nitrate/nitrite content and strengthened the antioxidant defense, with a decrease in the level of gastric lipid peroxidation, but increased the activities of CAT and SOD. Moreover, the effects of FBe are comparable to that of ranitidine, a reference drug. The obtained results suggest that this fermented barley extract prevented mice from H/E‐induced gastric mucosal damages through the suppression of inflammatory responses and oxidative stress‐responsive free radicals. Thus, FBe can be useful to treat patients suffering from gastric mucosal disorders as a potent food supplement, and thereby, it would increase the necessity of application in the food industry.

Effect of sodium metabisulfite on lipid peroxidation and enzyme activities in adult rat stomach and spleen

Sodium metabisulfite (NaMBS) has been used as an antioxidant and antimicrobial agent in a variety of drugs and foods. The aim of our study was to evaluate the effect of subchronic ingestion of NaMBS on lipid peroxidation, protein and enzymatic antioxidants in the gastric tissue and splenic Wistar rat. The rats were divided into four groups (n = 06 rats/group) as follows; Control (C), rats treated with 0.25% NaMBS (S0.25%), rats treated with 1% NaMBS (S1%) and rats treated with 4% NaMBS (S4%). NaMBS was administered to animals via drinking water. At the end of the experimental period, Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxi-dase (GPx), catalase (CAT) and thiols were determined. Redox status assess-ment revealed that 1% and 4% NaMBS doses induced gastric and spleen lipid peroxidation in animals compared to the control group. On the other hand, activities of SOD, GPx, CAT and thiols were reduced in the S1% and S4% groups in the stomach and spleen compared to the controls. Slight changes were detected in the GPx and CAT in the stomach of S0.25% group compared to the control group. In conclusion, the subchronic consumption of NaMBS has an adverse effect on the spleen and stomach by inducing oxidative damage leading to an increase in lipid peroxidation, protein oxidation and alteration of enzyme activity antioxidant.

Oral magnesium reduces gastric mucosa susceptibility to injury in experimental diabetes mellitus

This study investigated the effect of magnesium on the gastric defence mechanism in alloxan-diabetic male Wistar rats.Sixty rats were randomly divided into 2 groups, A (n=40) and B (n=20). Each group was subdivided into control, diabetic untreated (DU), diabetic magnesium (250mg/kg) treated (DMg250) and diabetic insulin (3IU/kgs.c) treated (DI). Diabetes was induced with alloxan (120mg/kg) and both groups were treated for 14days. By day 14, group A rats were sacrificed, the stomach excised and evaluated for histopathology, mucus content, parietal and mucus cell counts. Blood was withdrawn from the orbital sinus of group B rats for biochemical evaluation (blood glucose, superoxide dismutase (SOD), lipid peroxidation (LP) and nitric oxide (NO)) and later sacrificed for gastric SOD, LP and NO evaluation.Blood glucose level was reduced (p<0.05) in all treatment groups compared to DU. Gastric SOD, parietal and mucus cell counts were increased (p<0.05) in the DMg250 and DI compared to DU. Serum LP and NO were reduced while gastric LP was increased in the DMg250 compared to DU. Gastric NO and mucous content were significantly reduced (p<0.05) in all diabetic groups compared to control. The gastric mucosa of the DU group had haemorrhage, inflammation and parasites embedded. The DMg250 and DI had normal submucus and muscle layers with reduced inflammation.Oral magnesium treatment in diabetes exerts hypoglycaemic effects, reduces serum nitric oxide and lipid peroxidation, increases gastric superoxide dismutase, mucous cell count and reduces the susceptibility of the gastric mucosa to ulceration.

Strawberry Polyphenols Attenuate Ethanol-Induced Gastric Lesions in Rats by Activation of Antioxidant Enzymes and Attenuation of MDA Increase

Background and AimFree radicals are implicated in the aetiology of gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. Strawberries are common and important fruit due to their high content of essential nutrient and beneficial phytochemicals which seem to have relevant biological activity on human health. In the present study we investigated the antioxidant and protective effects of three strawberry extracts against ethanol-induced gastric mucosa damage in an experimental in vivo model and to test whether strawberry extracts affect antioxidant enzyme activities in gastric mucosa.Methods/Principal FindingsStrawberry extracts were obtained from Adria, Sveva and Alba cultivars. Total antioxidant capacity and radical scavenging capacity were performed by TEAC, ORAC and electron paramagnetic resonance assays. Identification and quantification of anthocyanins was carried out by HPLC-DAD-MS analyses. Different groups of animals received 40 mg/day/kg body weight of strawberry crude extracts for 10 days. Gastric damage was induced by ethanol. The ulcer index was calculated together with the determination of catalase and SOD activities and MDA contents. Strawberry extracts are rich in anthocyanins and present important antioxidant capacity. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious role. Antioxidant enzyme activities increased significantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found.ConclusionsStrawberry extracts prevented exogenous ethanol-induced damage to rats' gastric mucosa. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity of promoting the action of antioxidant enzymes. A diet rich in strawberries might exert a beneficial effect in the prevention of gastric diseases related to generation of reactive oxygen species.

Antioxidant effect of dry olive (Olea europaea L.) leaf extract on ethanol-induced gastric lesions in rats

Previous studies demonstrated that the damaging action of absolute ethanol could be attributed to the enhancement in the reactive oxygen species, increase in lipid peroxidation and inhibition of antioxidative enzyme activity. In this study we investigated the mechanism of protective effect of olive leaf extract (OLE), a natural antioxidant, on gastric mucosal damage induced by absolute ethanol in rats. OLE (80 mg/kg daily) was applied intragastrically (i.g.) two weeks prior to absolute ethanol administration. Areas of gastric lesions were measured and ulcer index (UI) was calculated. The effects of applied OLE on gastric mucosal lesions, malondialdehyde level and antioxidative enzyme (catalase and superoxide dismutase) activity were compared with effects of i.g. pretreatment of reference drug, ranitidine (50 mg/kg). Absolute ethanol administration caused severe gastric mucosal haemorrhage. Pretreatment with OLE, as well as with ranitidine, significantly (p < 0.001) attenuated the gastric lesions induced. Furthermore, OLE was effective in the prevention of an increase in gastric lipid peroxidation and in the prevention of a decrease in antioxidative enzyme activity. The results obtained indicate that OLE has gastroprotective activity against ethanol-induced gastric lesions in rats, possibly related to its antioxidative properties.

Effect of melatonin on burn-induced gastric mucosal injury in rats

We studied the effect of melatonin treatment on gastric mucosal damage induced by experimental burns and its possible relation to changes in gastric lipid peroxidation status. Melatonin was intraperitoneally applied immediately after third-degree burns over 30% of total body skin surface area of rats. Malondialdehyde (MDA), uric acid (UA) and sulphydril (SH) levels were determined in gastric mucosa and blood plasma and used as biomarkers of the oxidative stress. The results showed that the skin burn caused oxidative stress evidenced by accumulation of MDA and UA as well as the depletion of SHs in gastric mucosa. Plasma MDA concentrations were elevated, while plasma SH concentrations were decreased after burns. Melatonin (10 mg per kg body weight) protected gastric mucosa from oxidative damage by suppressing lipid peroxidation and activating the antioxidant defence. It may be hypothesised that melatonin restores the redox balance in the gastric mucosa and protects it from burn-induced oxidative injury. Melatonin has no significant influence on the concentrations of plasma MDA and antioxidants after burn; therefore, it should largely be considered as a limiting factor for tissue-damage.

Effect of Sesame Oil on Acidified Ethanol‐Induced Gastric Mucosal Injury in Rats

Exposure of gastric mucosa to concentrated ethanol induces acute gastritis. Gastric mucosal lipid peroxidation plays a significant role in the pathogenesis of ethanol-induced gastric mucosal lesions. The aim of this study was to investigate the effect of sesame oil on acidified ethanol-induced gastric mucosal damage in rats. We performed gastric bilateral vagotomy in rats. A small incision on forestomach was made and stomach content was expelled. Normal artificial gastric acid (54 mM NaCl plus 100 mM HCl) or acidified ethanol (30% ethanol plus 150 mM HCl) was instilled into the stomach. Gastric lipid peroxidation, glutathione, and nitric oxide levels were measured 3 hours after acidified ethanol administration. Acidified ethanol caused mucosal ulceration, luminal hemorrhage, lipid peroxidation, and a lower level of mucosal glutathione and nitric oxide production. Pretreatment of sesame oil, but not mineral oil, significantly decreased acidified ethanol-induced mucosal ulcer formation and luminal hemorrhage. Sesame oil reduced mucosal lipid peroxidation, as well as glutathione and nitric oxide production in acidified ethanol-treated stomachs. Furthermore, both sesame oil and mineral oil did not affect serum ethanol concentration in acidified ethanol-treated rats. Sesame oil attenuates acidified ethanol-induced gastric mucosal injury by reducing oxidative stress in rats.

The effects of some nonsteroidal anti-inflammatory drugs on experimental induced gastric ulcers in rats

Celecoxib is a frequently used nonsteroidal anti-inflammatory drug (NSAID) in the treatment of rheumatoid arthritis and osteoarthritis. It selectively inhibits cyclooxygenase II (COX-2) enzyme which is responsible for the production of proinflammatory prostanoids. It has been proposed that since it does not significantly inhibit COX-1, an isoenzyme responsible for the production of cytoprotective prostanoids, celecoxib has fewer side effects in the stomach. Dipyrone which is a drug with potent analgesic activity has no significant inhibitory effect on COX. In this study, the effects of celecoxib and dipyrone on experimentally induced gastric ulcers in rats were compared with respect to different parameters. In the first experiment, in an attempt to identify the best dose for both drugs, a histamine-induced gastric ulcer model was used and each drug was administered at 5, 25 and 100 mg/kg doses, and ulcer index, acidity and mucus secretion were measured in the stomach. The best dose was determined to be 5 mg/kg for both drugs. Celecoxib was found to delay ulcer healing when compared to dipyrone especially when ulcer index was used as measure. In the second experiment, ulcer index, acidity, mucus secretion, and the levels of myeloperoxidase (MPO), lipid peroxide (MDA), non-protein sulfhydryl groups (NP-SH), and prostaglandin E2 (PGE2) were investigated in the stomach of rats with gastric ulcers induced by histamine, stress and diethyldithiocarbamate (DDC). While celecoxib increased the ulcer index in stress-induced ulcer, dipyrone decreased the index in DDC-induced ulcer. Celecoxib also caused a significant increase of gastric mucus secretion in histamine-induced ulcer model. Gastric lipid peroxidation was significantly increased by dipyrone in the control group without gastric ulcer induction, whereas it was significantly increased by celecoxib in the histamine-induced and stress-induced ulcer groups. Dipyrone promoted a decrease in gastric NP-SH levels in the control group with stress-induced ulcer. With respect to gastric MPO activity, dipyrone caused a decrease in the histamine-induced ulcer group but it caused an increase in the stress-induced and DDC-induced ulcer groups. Gastric PGE2 levels in the control group without gastric ulcer induction were not affected by celecoxib while they were increased by dipyrone. In conclusion, celecoxib prompted the formation of experimentally induced gastric ulcers more than did dipyrone. The study was supported by Osmangazi University Research Funds.

Antioxidant activity of Cissampelos pareira on benzo(a)pyrene-induced mucosal injury in mice

Abstract This study evaluated the antioxidant activity of Cissampelos pareira (L.) Hirsuta (family: Menispermaceae). The roots of the C pareira (50% ethanol extract) were found to contain a large amount of polyphenols and exhibit significant and dose-dependent reducing ability, indicative of potent antioxidant ability both in vitro and in vivo. The C pareira extract (CPE) showed significant antioxidant activity in the 1,1-diphenyl-2-picrylhydrazyl assay. The ability of CPE to scavenge reactive oxygen and nitrogen species was tested; and it was found to significantly scavenge superoxide, hydrogen peroxide, hydroxyl radicals, and nitric oxide at a dose regimen of 50 to 400 μ g/kg in vitro. The CPE also inhibited hydroxyl radical–induced oxidation of proteins in vitro. The efficacy of CPE was further tested in vivo. It was found to exhibit a potent protective activity in an acute oxidative tissue injury animal model: benzo(a)pyrene-induced gastric toxicity in mice. Treatment with CPE at a dose regimen of 50 and 100 mg/kg body weight in mice, significantly and dose dependently protected the gastric mucosa against benzo(a)pyrene-induced oxidative stress. The CPE, significantly and dose-dependently, also afforded protection against gastric lipid peroxidation, glutathione levels, and activities of other antioxidant enzymes, namely, superoxide dismutase, catalase, glutathione peroxidase, and glutathione S -transferase. These results indicate the compelling antioxidant activity of C pareira in vitro and against the stress induced by the gastric carcinogen benzo(a)pyrene in vivo. This is the first report on the antioxidant properties of C pareira against benzo(a)pyrene.

Lead exposure increases oxidative stress in the gastric mucosa of HCl/ethanol-exposed rats

To investigate the role of reactive oxygen species in the ulcer-aggravating effect of lead in albino rats. Albino Wistar rats were randomly divided into three groups and treated orally with 100 mg/L (low dose) or 5000 mg/L (high dose) of lead acetate for 15 wk. A third group received saline and served as control. At the end of wk 15, colorimetric assays were applied to determine the concentrations of total protein and nitrite, the activities of the oxidative enzymes catalase and superoxide dismutase, and lipid peroxidation in homogenized gastric mucosal samples. Exposure of rats to lead significantly increased the gastric mucosal damage caused by acidified ethanol. Although the basal gastric acid secretory rate was not significantly altered, the maximal response of the stomach to histamine was significantly higher in the lead-exposed animals than in the unexposed control group. Exposure to low and high levels of lead significantly increased gastric lipid peroxidation to 183.2%+/-12.7% and 226.1%+/-6.8% of control values respectively (P<0.0). On the other hand, lead exposure significantly decreased catalase and superoxide dismutase (SOD) activities and the amount of nitrite in gastric mucosal samples. Lead increases the formation of gastric ulcers by interfering with the oxidative metabolism in the stomach.

Effects of Esomeprazole Magnesium on Nonsteroidal Anti-Inflammatory Drug Gastropathy

It has been proposed that tissue damage induced by nonsteroidal anti-inflammatory drugs is related to increased tissue free radical production with antioxidant depletion. We have shown that esomeprazole increases gastric total antioxidant capacity in mice and, therefore, hypothesized that the protective effect of esomeprazole during treatment with a nonsteroidal anti-inflammatory drug is related to increased gastric antioxidant capacity and decreased tissue free radical production. A/J mice received one of four treatments by daily gavage: saline in vehicle (control), indomethacin, esomeprazole, or indomethacin and esomeprazole. After 10 days, all mice were sacrificed and validated assays were used to measure gastric total antioxidant capacity, lipid peroxide levels, and myeloperoxidase activity. Indomethacin-treated mice developed weight loss and melena. No mice receiving indomethacin and esomeprazole died, but the death rate while receiving indomethacin was 38% (chi2, P = 0.05). Gastric lipid peroxide levels increased in mice receiving indomethacin treatment compared to treatment with esomeprazole and indomethacin (P = 0.03). There was a strong trend (P = 0.08) toward increased gastric total antioxidant capacity in mice receiving esomeprazole and indomethacin compared to mice receiving indomethacin. Gastric myeloperoxidase activities were not different among the four groups. Esomeprazole significantly improved survival in mice that received indomethacin, reduced free radical production, as estimated by lipid peroxide levels, and appeared to increase gastric total antioxidant capacity. The mechanisms for the beneficial effects of esomeprazole in the treatment of gastropathy are more complex than previously thought.

Gastric mucosal lesions in influenza virus infected mice: role of gastric lipid peroxidation.

The present study provides direct experimental proof that the combination of influenza virus infection A/Aichi/2/68 (H3N3) with different models of oxidative stress, such as immobilization, cold and cold-restraint, is associated with graduated oxidative disturbances in the stomach of mice, despite the absence of virus replication and inflammation in this tissue. It was found that experimental influenza virus infection is accompanied with significant changes in gastric mucosal integrity, as well as an increase in the products of lipid peroxidation in the stomachs of mice. Preliminary exposure of mice to immobilization stress and subsequent inoculation of influenza virus did not significantly influence gastric ulceration or lipid peroxidation compared with infected mice. Cold stress resulted in a significant decrease in the index of stomach ulceration and did not influence the fluorescent products of lipid peroxidation and MDA compared with infected animals. The simultaneous application of cold-restraint stress and influenza virus infection provoked synergism in the activity of all factors on the parameters under investigation. Ulceration increased approximately two-fold, as did the amount of fluorescent products of lipid peroxidation and MDA, compared with influenza virus-infected and non-stressed animals.

EFFECTS OF PARACETAMOL AND PROPACETAMOL ON GASTRIC MUCOSAL DAMAGE AND GASTRIC LIPID PEROXIDATION CAUSED BY ACETYLSALICYLIC ACID (ASA) IN RATS

We have studied the effect of paracetamol and its pro-drug propacetamol on gastric mucosal damage induced by acetylsalicylic acid (ASA) and its possible relation to changes in gastric lipid peroxidation status in rats. Paracetamol or propacetamol were administered intragastrically 1 h before ASA (300 mg kg −1) in the following equivalent doses: 62.5, 125.0 and 250.0 mg kg −1 or 125.0, 250.0 and 500.0 mg kg −1, respectively. The effects of the tested agents were compared to that of prostaglandin E2 (PGE2) 15, 30 and 60 mg kg −1. Gastric ulcer formation was estimated morphometrically 4 h after ASA administration. Malondialdehyde (MDA), glutathione (reduced, GSH, and oxidized, GSSG) and uric acid (UA) were determined in gastric mucosa and blood plasma and used as biochemical markers of the oxidative status. The results showed that paracetamol (250, 125, 62.5 mg kg −1) and propacetamol (500, 250, 125 mg kg −1) diminished the area of ASA-induced gastric lesions. The effect of propacetamol was more pronounced than that of paracetamol and similar to that of PGE2. Gastric MDA increased 3-fold in the ASA-group. The tested agents reduced it by a range of 30–70%. In all pretreated groups gastric glutathione and UA levels were found higher than that of control group and lower than that of ASA-group. Paracetamol and propacetamol, as well as PGE2, diminished the lipid peroxidation in plasma to a lesser extent than in gastric mucosa, but maintained elevated levels of the selective plasma antioxidant UA. These results show that the ASA-induced gastric mucosal damage is accompanied by the development of oxidative stress, evidenced by the accumulation of MDA, and concomitant initial activation of cell antioxidant defences. As paracetamol and propacetamol tend to decrease gastric lesions caused by ASA and alter gastric mucosal MDA, glutathione and UA values in a favorable manner, it could be suggested that their effects on the gastric mucosa could be related to interference with oxidative stress development.

Protective effects of zinc in indomethacin-induced gastric mucosal injury: evidence for a dual mechanism involving lipid peroxidation and nitric oxide.

Indomethacin causes gastric mucosal injury, although the pathogenesis is not fully understood. Zinc, is known to have gastroprotective effects in both humans and experimental animals. To determine (i) the protective effects of zinc in indomethacin-induced gastric mucosal injury in rats, and (ii) whether these cytoprotective effects are mediated by changes in gastric lipid peroxidation and/or nitric oxide synthase activity. Gastric lesions were induced in rats by the intragastric administration of indomethacin. Morphological changes, lipid peroxidation (malondialdehyde levels) and nitric oxide synthase activity were determined in animals pre-treated with zinc sulphate and in controls. Indomethacin significantly increased malondialdehyde levels and decreased NOS activity. These effects were attenuated by pre-treatment with zinc (P < 0.005 and 0.0001, respectively). The protective effects of zinc were readily abolished in animals pre-treated with N-nitro-L-arginine methyl ester (L-NAME). Morphologically, indomethacin induced large areas of mucosal ulcerations, which were completely prevented by zinc pre-treatment. Zinc provides protection against indomethacin-induced gastric mucosal injury. These protective effects result from the inhibition of lipid peroxidation and the preservation of mucosal nitric oxide synthase.

THE EFFECT OF CHRONIC STRESS ON HEPATIC AND GASTRIC LIPID PEROXIDATION IN LONG-TERM DEPLETION OF GLUTATHIONE IN RATS

The effect of chronic stress (immobilization and cold) on hepatic and gastric thiobarbituric acid reactive substances (TBARS) and vitamin C levels were investigated in rats having long-term depletion of glutathione (GSH) by applying buthionine sulfoximine (BSO). GSH and vitamin C levels decreased and TBARS levels increased in the liver and stomach of rats subjected to stress. Long-term BSO administration along with stress caused no additional changes in these parameters. These results may indicate that long-term glutathione depletion did not potentiate stress-induced hepatic and gastric lipid peroxidation.

The role of 5-HT 3 receptors in the anti-ulcer effect of calcitonin

1. 1. The aim of the present study was to determine the role of 5-HT 3 receptors of the gastroprotective effect of salmon calcitonin (sCT) and sCT-induced changes in gastric, hepatic, brain and brainstem glutathione (GSH) and lipid-peroxidation (LP) levels in rats subjected to cold-immobilization stress. 2. 2. Stress exposure resulted in ulcer formation and a decrease in GSH levels of the liver, brain and brainstem and an increase in gastric and hepatic LP ( P <0.05). 3. 3. sCT prevented stress-induced gastric ulcer development ( P < 0.01) and reversed the decrease in hepatic and brain GSH levels ( P < 0.05). 4. 4. In the present study, a 5-HT 3 receptor antagonist, ICS 205 930 was used. Interestingly, the effect of the blocker on GSH and LP levels of the tissues studied was similar to those of sCT. 5. 5. ICS 205 930 dose dependently reversed the anti-ulcer effect of sCT although it did not antagonize the effect of sCT on GSH and LP levels, but it seemed to show an additive interaction for brain and brainstem GSH and gastric LP levels with sCT.

Gastric lipid peroxidation, gluathione and calcium channel blockers in the stress-induced ulcer model in rats

The antiulcer activity of verapamil and its analogues devapamil and gallopamil was studied. All three drugs reduced cold-restraint stress-induced ulcer development. Gallopamil almost abolished gastric ulcers. Verapamil prevented the increase in gastric lipid peroxidation (LP) due to stress. On the other hand, devapamil and gallopamil increased gastric lipid peroxidation and decreased glutathione levels. This effect may be attributed to the increase in oxygen supply due to possible effective vasodilation at gastric mucosa. The second part of this study revealed that stress-induced gastric ulcers in rats rapidly and spontaneously heal and disappear within 24 h. During recovery, gastric LP decreased and glutathione levels increased within 12 h after the withdrawal of stress, preceded by an initial reduction in glutathione. After 72 h, an unexplained increase in gastric LP and a decrease in glutathione were observed. Treatment with verapamil, devapamil and gallopamil promoted healing, gallopamil being again the most effective. Their effects on gastric LP and glutathione levels are in accordance with the results of pretreatment experiments. In conclusion, devapamil and gallopamil are effective antiulcer agents against stress-induced ulcers, but unlike verapamil, antioxidant activity does not seem likely to be among their mechanisms of action.