Desynchronosis and erosive and ulcerative lesions of the stomach in rats active or passive in the open-field test: effect of exogenous melatonin

We studied the effect of a phase shift in circadian rhythms (desynchronosis) on the development of erosive and ulcerative lesions in the gastric mucosa in male Wistar rats with different behavioral activity in the open-field test. The animals kept under conditions of natural or shifted light-dark cycle were untreated or intraperitoneally received physiological saline (1 ml) and melatonin (1 or 2 mg/kg). Desynchronosis induced gastric ulcers in active rats not receiving injections or intraperitoneally injected with physiological saline. No gastric ulcers were found in passive animals kept under shifted light-dark cycle. Melatonin induced gastric ulcers in passive animals kept under natural light-dark cycle. Gastric ulcers were not found in active rats subjected to desynchronosis and receiving melatonin. Our results indicate that treatment with melatonin for the correction of changes induced by shifts in the light-dark cycle should be performed taking into account individual behavioral characteristics.     

Effect of semax on homeostasis of gastric mucosa in albino rats

The ACTH_4–7 analogue Semax administered intrapeitoneally in a dose of 50 μg/kg 1 h before exposure to ulcerogenic factors (ethanol, water immersion immobilization stress) protected gastric mucosa from damage. Postoperative treatment with Semax for 5 days after application of glacial acetic acid on the mucosa prevented acetic acid-induced ulcers and promoted their healing. The antiulcer effects of Semax in the studied dose were comparable with those of tripeptide Pro-Gly-Pro in a dose of 1 mg/kg. Translated fromByulleten “Eksperimental'noi Biologii i Meditsniy, Vol. 130, No. 9, pp. 300–302, September, 2000     

Effect of buspiron on formation of acquired helplessness

By decreasing anxiety and emotional stress, buspiron in doses of 1 and 5 mg/kg decelerates the formation of instrumental defense reflex and increases the incidence of acquired helplessness in rats trained under conditions of highly indefinite environment. Buspiron in a dose of 0.5 mg/kg apparently does not affect the optimal emotional background, thus promoting attaining the goal of conditioned reflex activity and not leading to an increase in the incidence of acquired helplessness. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 9, pp. 286–288, September, 1998     

Differences in behavioral patterns and resistance to stress-induced gastric ulceration between August and Wistar rats adapted and unadapted to hypoxia

The incidence of gastric ulceration induced by acute emotional stress in Wistar rats is 3 times higher than in August rats, and the mean number of gastric ulcers in Wistar rats 6.3-fold surpassed that in August rats. Wistar rats predisposed to stress-induced ulceration displayed suppressed locomotor and exploratory activities in the open field test, while August rats had more stable behavioral patterns and enhanced exploratory activity after stress. Short-term preadaptation to hypobaric hypoxia for 6 days attenuated stress-induced gastric ulceration, whereas long-term adaptation (40 days) aggravated the severity of gastric ulcers in August and Wistar rats. The interstrain differences in stress-induced ulceration persisted after adaptation. The data suggest that these differences are related to genetically determined peculiarities of production and metabolism of NO and glucocorticoids in August and Wistar rats. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 12, pp. 638–641, December, 1999     

Effect of melatonin on the thymus, adrenal glands, and spleen in rats during acute stress

We studied the effects of acute stress and exogenous melatonin on stress marker organs in rats. Administration of melatonin under normal conditions increased the relative weights of the thymus (active rats) and adrenal glands (active and passive rats). The relative weight of the spleen also tended to increase after melatonin treatment. Stress led to involution of the thymus and hypertrophy of the adrenal glands in active and especially in passive animals receiving physiological saline. Melatonin partially or completely prevented involution of the thymus under stress conditions. Stress had no effect on the relative weight of the adrenal glands in melatonin-treated rats. The relative weight of the spleen in active rats receiving melatonin in doses of 0.5 and 1 mg/kg decreased after stress exposure. Our results suggest that melatonin modulates the hemodynamics and function of stress marker organs. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 3, pp. 263–266, March, 2006     

Effect of melatonin on cyclic nucleotide content and intensity of lipid peroxidation in the hippocampus and habenula of rats exposed to acute hypoxia

Single intraperitoneal injection of melatonin in a dose of 1 mg/kg prevented accumulation of cGMP and intensification of lipid peroxidation in the hippocampus and habenula of rats exposed to acute hypobaric hypoxia (12,000 m). Changes in habenular content of cGMP suggest that melatonin prevents hypoxia-induced activation of heme-oxygenase. Translated fromByulleten' Eksperimental" noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 168–171, August, 2000     

Gastric healing effect of melatonin against different gastroinvasive agents in cholestatic rats

Background and objective: The frequency of gastrointestinal ulceration is higher in jaundiced patients than in healthy population. The aim of this study was to assess the effect of pretreatment with melatonin, a potent scavenger of reactive oxygen species, on stress-induced gastric ulcers of cholestatic rats. Materials and methods: Cholestasis was induced by surgical ligation of bile-duct and sham-operated rats served as sham animals. The animals received saline or melatonin (1, 3 or 10 mg/kg) before stress induction. Three different types of gastroinvasive agents including ethanol, indomethacin or water immersion were used as stress agents to induce gastric ulceration. Results: Gastric mucosal damage induced by different gastroinvasive agents was significantly greater in bile-duct-ligated rats than in sham ones. Melatonin was protective against ethanol-, indomethacin- and water immersion-induced gastric damage in bile-duct-ligated and sham rats, dose-dependently, but the protective effect of melatonin was greater in cholestatic rats than sham rats in all three different series of experiments. Conclusions: In conclusion, pretreatment of rats with melatonin protected gastric mucosa of cholestatic rats more effectively than the sham ones possibly by a mechanism involving the scavenging of free radicals.     

Effect of trimetazidine on cerebral metabolism during acute ischemia complicated by hypoxia

In experiments on rats, trimetazidine (25 mg/kg) prevented disturbances in energy metabolism and LPO activation in the brain under conditions of acute ischemia aggravated by hypoxia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 2 pp. 142–144, February, 2000     

Effect of levodopa on the healing of neurogenic degenerative lesions of the gastric mucosa in rats

Neurogenic degeneration of the gastric mucosa was produced in rats by immobilizing the animals for 3h and by electrical stimulation. At the end of stimulation hemorrhagic erosions had developed in the gastric mucosa and they were still present 48 h later. Macroscopic and microscopic investigations showed that injections of levodopa into the rats in a dose of 10 mg/kg for 2 days after the end of stimulation accelerated the healing of hemorrhagic erosions of the mucosa.Laboratory of Experimental Pharmacology, Department of Pharmacology, Scientific-Research Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Central Research Laboratory, Leningrad Pediatric Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR S. V. Anichkov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 11, pp. 1347–1349, November, 1976.     

Role of neutrophils in a rat model of gastric ulcer recurrence caused by interleukin-1 beta.

The production of several cytokines such as interleukin (IL)-1 in gastric mucosa is increased in subjects infected with Helicobacter pylori, a bacterium associated with ulcer recurrence. This study was performed to determine whether the administration of IL-1 beta can cause recurrence of gastric ulcers in rats. Rats with healed ulcers received an injection of IL-1 beta (0.01 to 1 microgram/kg) or vehicle alone. Some rats received an injection of antiserum to rat neutrophils at the same time as 1 microgram/kg IL-1 beta or an injection of monoclonal antibodies against adhesion molecules (anti-intercellular adhesion molecule-1, anti-CD11a, and anti-CD11b) at 0, 12, and 24 hours after the initial injection. At this dose of IL-1 beta, the numbers of neutrophils and monocytes/macrophages infiltrating the scarred mucosa were higher at 12 and 24 hours than without injection of IL-1 beta. By 48 hours, seven of the eight bealed ulcers in the group treated with 1 microgram/kg IL-1 beta had recurred, as had one of the seven healed ulcers in the group given 0.1 microgram/kg IL-1 beta. No recurrence was found in the rats treated with 0.01 microgram/kg IL-1 beta or vehicle alone. Treatment with antiserum to neutrophils or antibodies to adhesion molecules inhibited both neutrophil infiltration into the scarred mucosa and the ulcer recurrence caused by IL-1 beta. These findings suggest possible mechanisms of recurrence of human peptic ulcers.     

Gastric and duodenal anti-ulcer activity of sulpiride,a dopamine D2 receptor antagonist,in rats

The gastric and duodenal anti-ulcer activity of sulpiride, a dopamine D₂ receptor antagonist, was studied on various types of experimentally induced ulcers in rats, viz., pylorus ligation and water immersion + restraint stress-induced gastric ulcers, gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs and reserpine, and duodenal ulcers induced by cysteamine hydrochloride. It has been found to possess significant anti-ulcer activity against all these models. In 19 h pylorus ligated rats, it significantly reduced the gastric secretion, increased the fucose and sialic acid concentration of the gastric juice and reduced its protein content, thus increasing the total carbohydrate: protein (TC/PR) ratio. These results suggest that the antisecretory and gastric mucosal barrier strengthening effects of sulpiride may be responsible for its anti-ulcer activity. A central component also appears to be involved in its anti-ulcer action against water immersion + restraint stress model. The results of this study provide a rationale for its beneficial effect seen in the therapy of peptic ulcer disease.     

A synergistic interaction between aspirin,or other non-steroidal anti-inflammatory drugs,and stress which produces severe gastric mucosal damage in rats and pigs

A synergistic interaction was observed in the development of damage to the gastric mucosa of rats following the administration of a single oral dose of 50 or 200 mg/kg body weight aspirinand exposure to brief periods of cold or restraint stress. Under the experimental conditions employed, the stressed (control) animals did not develop any visible signs of damage while the rats given only aspirin developed typical small erosions. However, the animals given aspirin and simultaneously exposed to stress developed a large number of deep ulcers and massive haemorrhage. Similar results were obtained in rats given a variety of non-steroidal anti-inflammatory drugs, but not with dextropropoxyphene—an analgesic devoid of ulcerogenic activity. In pigs, the chronic administration of aspirin and exposure to restraint stress resulted in the formation of deep crater-like ulcers. Only small focal lesions were found in the pigs given aspirin alone and no mucosal damage was evident in the pigs exposed only to stress. It appears that the aspirinplus stress synergism may be the basis for the formation of chronic gastric ulcers in humans.     

Incoordination of gastroduodenal myoelectric activity caused by immobilization stress in rabbits

Incoordination of gastroduodenal myoelectric activity in rabbits under immobilization stress was manifested, first, in an earlier resumption of spike activity in the duodenum than in the stomach and pyloric sphincter after its simultaneous suppression in these three parts of the gastrointestinal tract and, second, in the subsequent considerable increase of duodenal spike activity over its baseline level, while stomach and pyloric sphincter activities remained reduced. The incoordination of gastroduodenal myoelectric activity, which developed during the first hour of immobilization, was accompanied by the formation of erosive lesions in the gastric mucosa. The results of this study suggest that incoordination of gastroduodenal motor activity may be implicated in stressinduced gastric ulcers as a factor that damages the gastric mucosa by slowing down the evacuation of stomach contents and promoting duodenogastric reflux. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 3, pp. 239–242, March, 1995     

Cytoprotective and Antioxidant Effects of the Methanol Extract of Eremomastax Speciosa in Rats

Background

Ethno-botanical information shows that Eremomastax speciosa is used in the traditional management of various stomach complaints including gastro-duodenal ulcers.

Materials and Methods

In this study, we tested the cytoprotective potential of the whole plant methanol extract (100–200 mg/kg, p.o), against HCl/ethanol, absolute ethanol, cold/restraint stress rats, and pylorus legated rats pre-treated with indomethacin. The effects of the extract on gastric lesion inhibition, the volume of gastric juice, gastric pH, gastric acid output, mucus production and gastric peptic activity were recorded. Oxidative stress parameters were measured in blood and gastric tissue samples obtained from the animals in all the models tested.

Results

The extract significantly (p<0.05), reduced the formation of cold/restraint ulcers by (31–60%, inhibition), completely inhibited (100%) the formation of lesions induced by HCl/ethanol at the highest dose, but was less effective against absolute ethanol (22–46% inhibition). The extract (200 mg/kg), significantly reduced lesion formation (P<0.01), gastric acidity (P<0.01), and volume of gastric secretions (P<0.05), in the indomethacin/pylorus ligation model, and did not affect the activity of pepsin in gastric juice. Blood concentrations of antioxidant enzymes (catalase, SOD and GSH), increased significantly and MDA concentrations decreased in all models tested.

Conclusion

Cytoprotection by E. speciosa methanol extract was attributed to its ability to reduce acid secretion, and to enhance mucosal defence and in vivo antioxidant status.     

Dynamics of changes in skin lipids after stress: Effects of exogenous melatonin

Changes in the skin lipid composition induced by water-immersion stress in rats treated and untreated with melatonin were studied by thin-layer chromatography. Skin lipids showed a delayed reaction to stress. Melatonin exerted a protective effect which was manifested on the 2nd day after treatment in restoration of the level of total lipids and the absolute content of the majority of lipid fractions. The data suggest modification of, the metabolic relationships between skin lipids as well as lipids of the blood and subcutaneous adipose tissue. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 5, pp. 519–522, May, 1999     

Lack of evidence of omeprazole genotoxicity in Sprague-Dawley rats

Omeprazole is a proton pump inhibitor of increasingly wide usein the treatment of peptic ulcers. Although omeprazole has beensubjected to an extensive range of genotoxicity tests, whichhave all been concluded as negative, the ability of this compoundto interact with DNA and elicit unscheduled DNA synthesis inthe rat gastric mucosa has been the subject of debate. Therefore,we have examined omeprazole using other genotoxicity end-points.In female Sprague-Dawley rats, the administration by the oralroute of 100 mg/kg, either as neutral (pH 7.0) suspension oras suspension acidified to pH 1.5, which favours its transformationinto the active form of sulphenamide, did not induce DNA fragmentationin gastric mucosa and liver, as detected by the alkaline elutiontechnique. In the same experimental conditions, a frequencyof total nuclear anomalies (micronuclei, pyknosis and karyorrhexis)that was significantly higher than in controls was detectedwith both types of suspension in forestomach and descendingcolon mucosa. However, in both tissues this higher frequencyof nuclear anomalies was mostly due to pyknosis and karyorrhexis,which may be the outcome of a non-genotoxic effect, whereasthere was no significant increase in the number of micronucleatedcells, and this suggests the absence of clastogenic activity.Finally, in rats initiated with N-nitrosodiethylamine, the oraladministration of 100 mg/kg omeprazole for 14 successive daysproduced a modest but statistically significant increase ofliver -glutamyltranspeptidase positive foci, which is consistentwith a potential promoting activity. Taken as a whole and comparedwith previous findings our results add further doubts aboutthe undiscriminated capability of omeprazole to behave as agenotoxic carcinogen and provide evidence that the occurrenceof a genotoxic effect, if it actually takes place, is limitedto some strains of rats. ¹To whom correspondence should be addressed     

Lipid peroxidation in the brain and liver of rats during acute stress and melatonin treatment

We studied the effects of acute stress and exogenous melatonin in various doses on the intensity of lipid peroxidation in emotiogenic structures of the brain and liver of rats with different activity in the open field. Stress had no effect on the content of malonic dialdehyde in the hypothalamus, sensorimotor cortex, and liver of active and passive rats receiving physiological saline. The influence of melatonin on malonic dialdehyde content depended on the dose of this substance. The amount of malonic dialdehyde in brain structures (active and passive rats) and liver (active rats) increased after administration of exogenous melatonin in doses of 0.5 and 2 mg/kg, but decreased after treatment with the hormone in a dose of 1 mg/kg. Melatonin in various doses decreased malonic dialdehyde content in the liver of passive rats. The effects of melatonin are partly related to modulation of lipid peroxidation in central and peripheral tissues of the organism. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 7, pp. 19–23, July, 2004     

Protective Effect of Dermorphin Analogue Sedatin on Indomethacin-Induced Injury to the Gastric Mucosa

Administration of indomethacin (250 mg/kg) to mice was followed by the formation of severe ulcerative and erosive injury to the gastric mucosa, inhibition of DNA synthesis, and development of oxidative stress. Fivefold pretreatment with sedatin (100 μg/kg) decreased the area of indomethacin-induced ulcers and erosions, stimulated DNA synthesis, and reduced the severity of oxidative stress. Non-arginine dermorphin analogue did not stimulate DNA synthesis and had no effect on the degree of oxidative stress. After pretreatment with L-NAME, sedatin did not modulate the synthesis of DNA under conditions of indomethacin-induced injury to the gastric mucosa.     

Effect of glutamate and antagonists of N-methyl-D-aspartate receptors on experimental parkinsonian syndrome in rats

Ontranigral administration of glutamate to rats with parkinsonian syndrome induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine augmented the development of parkinsonian symptoms (oligokinesia and muscular rigidity), but did not affect motor activity of intact animals. Memantine administered intraperitoneally in parallel with induction of parkinsonian syndrome weakened the development of oligokinesia and muscular rigidity in a dose-dependent manner starting from 5 mg/kg and abolished toxic effect of glutamate. Ketamine (15 mg/kg) under the same conditions less potently prevented the development of oligokinesia, did not prevent the development of muscular rigidity, and did not antagonize glutamate toxicity. The data attest to an important role of glutamate and activation of N-methyl-D-aspartate receptors in the induction and development of parkinsonian syndrome. Translated fromByulleten' Eksperinmental'noi Biologii i Meditsiny, Vol. 130, No. 7, pp. 20–23, July, 2000     

Effect of the COX-2 Selective Inhibitor L-745,337 on Inflammation and Organ Prostaglandin E2 (PGE2) Levels in Adjuvant Arthritic Rats

The anti-inflammatory activity of the cyclooxygenase-2 inhibitor, L745,337, was assessed in adjuvant arthritic rats (AA). The relationship between PGE₂ organ levels and drug activity or adverse effects was determined. Arthritic rats were orally treated for two weeks with L-745,337 (0.1, 1 and 5 mg/kg/day), indomethacin (1 mg/kg/day) or vehicle and paw swelling was determined. At the end of the study, samples from paw, stomach (wall and mucosa) and kidney were obtained from rats with or without treatment at high doses of L-745,337 or indomethacin and PGE₂ levels were determined. The L-745,337 anti-inflammatory effective-dose-50 was 0.4 mg/kg. Maximal anti-inflammation was obtained with L-745,337 or indomethacin at doses of 5 and 1 mg/kg respectively. L-745,337 showed anti-arthritic activity. No stomach ulcers appeared in either untreated or treated arthritic and healthy control rats. In AA rats, PGE₂ increased in paw, stomach wall, gastric mucosa and kidney. These levels were lower in all organs after both drugs but not below PGE₂ control levels.