Effect of sialoadenectomy on adaptive cytoprotection in the rat

In the present study we have investigated the effect of sialoadenectomy in the rat on adaptive cytoprotection induced by intragastric instillation of an irritant concentration of ethanol (10% wt/vol). Gastric mucosae were examined 1 h after oral administration of 100% ethanol. In animals with intact salivary glands, pretreatment with saline was followed 15 min later by 100% ethanol. This treatment was associated with a significant degree of mucosal damage. However, prior administration of 10% ethanol in place of saline reduced the area of ulceration. In sialoadenectomized rats, the irritant concentration of ethanol did not protect the gastric mucosa from the damaging actions of absolute ethanol. The effect was partially restored if sialoadenectomized rats were treated for 3 days with an aqueous extract of rat salivary gland tissue. Histologic examination revealed no differences in the extent of epithelial damage or adherent mucus between rats with intact salivary glands and sialoadenectomized rats following pretreatment with either saline or 10% ethanol. Although adaptive cytoprotection in animals with intact salivary glands was not associated with increases in mucosal capacities for prostaglandin E2 or 6-keto prostaglandin F1 alpha biosynthesis, sialoadenectomy resulted in a reduction in the mucosal biosynthetic capacities for both prostanoids. Salivary gland extract administration to sialoadenectomized rats did not significantly alter mucosal prostaglandin biosynthesis levels. These data suggest that salivary gland factors affected adaptive cytoprotection induced by an irritant dose of ethanol. Although endogenous prostaglandin biosynthesis capabilities do not appear to be altered in adaptive cytoprotection, salivary factors appear to influence mucosal generation of prostaglandins.     

褪黑激素对应激性溃疡大鼠胃黏膜诱生型一氧化氮合酶表达的影响

背景胃黏膜诱生型一氧化氮合酶(iNOS)的过度表达在应激性溃疡的发生中起重要作用。目的研究褪黑激素(MT)对水浸鄄束缚应激大鼠胃黏膜iNOS表达的影响及其对胃黏膜的保护作用,以进一步阐明MT的作用机制。方法正常对照组不予水浸鄄束缚应激和MT预防,模型组和MT低剂量预防组、MT高剂量预防组于应激前30min分别腹腔注射含1%二甲基亚砜(DMSO)或MT5mg/kg、20mg/kg的等体积生理盐水。应激6h后处死动物,检测各组大鼠胃黏膜一氧化氮(NO)水平、iNOS蛋白和iNOSmRNA的表达,并评估胃黏膜损伤程度。结果水浸鄄束缚应激6h后,大鼠胃黏膜NO水平、iNOS蛋白和iNOSmRNA表达显著增加,胃黏膜病变明显。MT预防组大鼠胃黏膜NO水平、iNOS蛋白和iNOSmRNA表达均显著低于模型组(P<0.01),且溃疡指数(UI)显著下降(P<0.01)。MT高剂量预防组大鼠各检测指标均显著低于MT低剂量预防组(P<0.05),作用呈剂量依赖性。结论MT可预防水浸鄄束缚应激诱导的大鼠胃黏膜损伤,其机制可能与其抑制胃黏膜iNOS过度表达有关。     

Role of epidermal growth factor in healing of chronic gastroduodenal ulcers in rats

The healing of acetic acid-induced gastric and duodenal ulcers was examined together with biochemical indices of growth in gastric and duodenal mucosa in rats with intact or removed salivary glands after treatment with epidermal growth factor (EGF) or somatostatin, or both. After the extirpation of salivary glands, the healing rate of gastric and duodenal ulcerations was delayed and gastric content of immunoreactive EGF was reduced. This was accompanied by a significant decrease in the contents of deoxyribonucleic acid and ribonucleic acid in the gastric and duodenal mucosa. Repeated administration of EGF either subcutaneously or orally accelerated the healing of gastroduodenal ulcers in rats with intact salivary glands and completely reversed the delay in ulcer healing in sialoadenectomized animals. These effects were also accompanied by a significant increase in the growth parameters of gastric and duodenal mucosa. Administration of somatostatin, which prevented the growth-promoting action of subcutaneous EGF, resulted in a significant decrease in the EGF-stimulated healing of gastric and duodenal ulcerations in both intact and sialoadenectomized rats. Our findings suggest that cell proliferation is an important factor in healing of gastric and duodenal ulcerations and that EGF plays an important role in ulcer healing due to its mitogenic action.     

Effect of sialoadenectomy on gastric mucosal integrity and growth in the rat

The effect of removal of the submandibular-sublingual salivary gland (sialoadenectomy) has been examined in terms of the effects on the susceptibility of the gastric mucosa to the inflammatory and damaging actions of ethanol. In addition, the effects of sialoadenectomy on cell turnover in the gastric mucosa has been examined. Animals were examined at one to five weeks after removal of the submandibular-sublingual salivary gland complex. In response to 100% w/v ethanol, sialoadenectomized rat displayed greater hemorrhagic damage to the gastric mucosa than sham-operated control rats. The difference between sialoadenectomized and sham control rats was significant at two to five weeks after surgery. The rate of [³H]thymidine incorporation into gastric mucosa was significantly reduced in sialoadenectomized rats at one and two weeks. Mucosal DNA concentration was significantly reduced in sialoadenectomized rats at four and five weeks after surgery. Mucosal myeloperoxidase activity was greater in sialoadenectomized rats treated with ethanol compared to control animals, but this difference was only significant at two weeks after surgery. Sialoadenectomy was also associated with a reduction in duodenal and gastric mucosal levels of immunoreactive epidermal growth factor (EGF). Differences between sialoadenectomized and control rats were not significant until three to four weeks after surgery. These data indicate that sialoadenectomy was associated with an increase in the susceptibility of rat gastric mucosa to ethanol-mediated damage. Sialoadenectomy also resulted in a reduction in gastric mucosal growth and gastroduodenal mucosal levels of EGF. However, the influence of sialoadenectomy on the susceptibility of the rat gastric mucosa to ethanol-mediated damage occurred prior to any significant effect on mucosal DNA concentration or EGF levels.This work was supported by a grant from the Medical Research Council of Canada, Grant No. MT6426.     

Effect of glutathione on gastric mucosal lesion induced by restraint water-immersion in rats

AIM To determine the effect of glutathione (GSH) on stress gastric mucosal lesion.METHODS The stress gastric mucosal lesion as produced by restraint water-immersion in rats and gastricmucosal lesion, gastric mucosal GSH content, gastric acid secretion and gastric barrier mucus secretion wereexamined. We also observed the effect of GSH on gastric mucosal lesion and the effect of N-ethylmaleimine(NEM) and indomethacin on GSH protection. Comparisons between two groups were made using the Students t test.RESULTS GSH (100 and 200 mg/kg) intraperitoneally protected against stress gastric mucosal lesion(P<0.001 and P<0.001). Restraint water-immersion stress significantly reduced gastric mucosal GSHcontent (P < 0.001), but pretreatment with GSH (100 mg/kg) had no effect on gastric mucosal GSH content(P>0.05). The preinjection of NEM (10 mg/kg, sc.), a sulfhydryl-blocking reagent, or indomethacin(5 mg/kg, im.), a cyclooxygenase inhibitor, had no effect on protection of GSH (P>0.05). GSH(100mg/kg) significantly increased secretion of gastric barrier mucus (P<0.05), but had no effect onsecretion of gastric acid in restraint water-immersed rats (P >0.05).CONCLUSION GSH can inhibit the formation of gastric mucosal lesions induced by restraint water-immersion. The protective effect of GSH was due, in part, to promoting the secretion of gastric barriermucus, but not to suppress the gastric acid secretion. The protection effect of GSH has no relation withgastric mucosal GSH and PGs.     

Selective adenosine A receptor agonist, ATL-146e, attenuates stress-induced gastric lesions in rats

BACKGROUND: Activation of adenosine A(2A) receptors reduces the production of various pro-inflammatory cytokines and suppresses neutrophil activation. Water-immersion restraint is well known to cause gastric mucosal lesions due to stress. The pathogenesis of stress-induced gastric mucosal lesions is characterized by activation of inflammatory cells and production of inflammatory cytokines. Agonists of adenosine A(2A) receptors are known to be anti-inflammatory, but the effects of these compounds on the development of gastric mucosal lesions has not been reported. In the present study, the effect of a potent and selective adenosine A(2A) receptor agonist, ATL-146e, on water-immersion stress-induced gastric mucosal lesions was studied. METHODS: Rats were subjected to water-immersion stress with or without pretreatment with a single intraperitoneal injection of a potent and selective agonist of the adenosine A(2A) receptor. The gastric concentrations of myeloperoxidase (MPO), as an index of neutrophil accumulation, and the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), were measured. RESULTS: The total length of gastric erosions (ulcer index) in control rats was 21.6 +/- 3.23 mm and was reduced by 86% to 3.1 +/- 0.83 mm by pretreatment with 5.0 microg/kg ATL146e (P < 0.001). The gastric content of MPO, TNF-alpha and IL-1beta were all increased after water-immersion stress and reduced to near normal levels by ATL-146e. CONCLUSION: A specific adenosine A(2A) agonist inhibits stress-induced gastric inflammation and damage. A(2A) agonist compounds may be useful for preventing ulcers and appear to act by blocking gastric inflammation.     

Effects of FK506, an immunosuppressive agent,on genesis of water-immersion stress-induced gastric lesions in rats

We examined the effects of FK506, an immunosuppressive agent, on the genesis of water immersion stress-induced gastric lesions in rats. Using high-performance liquid chromatography, four kinds of prostaglandins, ie, 6-keto-prostaglandin F₁, prostaglandin F₂, prostaglandin E₂, and prostaglandin D₂, were detected, and no leukotrienes were detected in gastric mucosa in rats without stress. After 6 hr of stress, gastric lesions developed with decreases in all prostaglandin contents, and the emergence of peptide leukotrienes was observed. Intramuscular administration of FK506 (0.1, 0.25, 0.5, 1.0, and 2.0 mg/kg) reduced lesion index dose-dependently. Administration of FK506 at doses over 0.25 mg/kg decreased all prostaglandin contents, but did not affect the increase in leukotriene contents. Pretreatment with famotidine or omeprazole reduced lesion index, and the protective effects were equivalent to those of 1.0 mg/kg of FK506, although FK506 did not affect gastric secretion during water-immersion stress. Water-immersion stress did not change the activities of xanthine oxidase in either stomach or serum. Polyoxyethylenemodified superoxide dismutase did not prevent gastric lesions. Water-immersion stress significantly increased myeloperoxidase activity in gastric mucosa, and FK506 reduced the increase in myeloperoxidase activity induced by stress. From our results, other factors besides gastric acid secretion and tissue eicosanoid contents, such as chemoattractant factor, might also be involved in the genesis of water-immersion stress-induced gastric lesions in rats.     

Delayed gastric ulcer healing after extirpation of submandibular glands is sex-dependent

This study examines the effect of excision of the submandibular salivary glands, the main source of epidermal growth factor (EGF), and the role of gender on the healing of acetic acid-induced gastric ulcers in rats. In male rats excision of the submandibular glands delayed ulcer healing. At 15 and 25 days the unhealed ulcer areas were significantly larger in the sialoadenectomy group than in control animals, and fewer completely healed ulcers were seen in this group at 25 days. Ulcer healing in female rats was slower. At day 25 ulcers were healed in 12% of female rats with intact salivary glands, compared with 68% in males. Female rats also showed larger unhealed ulcer areas after sialoadenectomy than controls. We conclude that removal of the main source of EGF in the gastrointestinal tract is associated with a delay in healing of gastric ulcers. The significant difference in healing observed between female and male rats may be influenced by the known androgenic regulation of EGF production in the salivary glands.     

Healing of chronic gastroduodenal ulcerations by antacids

Antacids show gastroprotective action against various irritants in experimental animals and enhance the healing of chronic gastroduodenal ulcers in humans but the mechanisms of these effects are unknown. The present study was designed to determine whether prostaglandin (PG) and epidermal growth factor (EGF), which also have protective and antiulcer properties, contribute to the action of antacids on rat's stomach. It was found that Maalox 70 and its active component, Al(OH)₃, enhance significantly the healing of chronic gastric and duodenal ulcers observed during 7 and 14 days after their induction. Pretreatment with indomethacin caused a significant prolongation of ulcer healing, and this was accompanied by a significant reduction in PG and EGF formation, suggesting that both factors may be involved in ulcer healing. Maalox and Al(OH)₃ failed to prevent the suppression of PG by indomethacin but were equally effective in ulcer healing in rats without and with indomethacin administration, suggesting that endogenous PG may not play any important role in the healing process by these drugs. Removal of salivary glands, the major source of EGF, also prolonged ulcer healing but, again, Maalox was as effective in ulcer healing as in rats with intact salivary glands. Our findings that Maalox at pH above 3.0 binds significant amounts of EGF, enhances the binding of EGF to the ulcer area, and stimulates mucosal growth, suggest that EGF may be involved in ulcer healing; however, because antacids are also effective after sialoadenectomy, EGF does not seem to be the major factor in ulcer healing by these drugs.     

Roles of nocturnal melatonin and the pineal gland in modulation of water-immersion restraint stress-induced gastric mucosal lesions in rats

The roles of melatonin and the pineal gland in the circadian variation of water-immersion restraint stress-induced gastric mucosal lesions in rats were investigated. Fasted rats were subjected to water-immersion restraint stress during both the diurnal and nocturnal phases of a light:dark cycle. Pinealectomized and sham-operated rats were also subjected to water-immersion restraint stress at night. The lesion area after 4 hr of stress during the dark phase was significantly lower than in light-phase controls. Pinealectomy increased the lesion area in the dark phase, compared to the sham operation, but this effect was counteracted by intracisternal melatonin preadministration at a dose of 100 ng/rat. Melatonin concentrations in control rats during the light phase were significantly increased 4 hr after water-immersion restraint stress. In contrast, melatonin concentrations 4 hr after water-immersion restraint stress in the dark phase were significantly depressed compared with the control levels at the corresponding time. Melatonin levels after stress exposure were markedly decreased in pinealectomized rats as compared with sham-operated rats. These results suggest that circadian rhythm has an important role in the formation of stress-induced gastric mucosal lesions in rats and that melatonin responses to water-immersion restraint stress differ between day and night. The pineal gland modulates the stress response and melatonin contributes to gastric protection via a mechanism involving the central nervous system.     

Implications of reactive oxygen species and cytokines in gastroprotection against stress-induced gastric damage by nitric oxide releasing aspirin

BACKGROUND AND AIMS: Nitric oxide-releasing aspirin (NO-ASA) has been shown to inhibit cyclo-oxygenase and prostaglandin generation without causing mucosal damage, but the role of reactive oxygen species (ROS) and cytokines in the action of ASA and NO-ASA against acute gastric damage has been little studied. METHODS AND MATERIALS: We compared the effect of NO-ASA and ASA on gastric lesions provoked by water-immersion and restraint stress (WRS), ischemia-reperfusion, and 100% ethanol. We determined the number and area of gastric lesions, gastric blood flow (GBF), plasma concentration of proinflammatory cytokines IL-1beta and TNFalpha, expression of superoxide dismutase (SOD) and glutathione peroxidase (GPx), ROS generation, and the malondialdehyde (MDA) concentration as an index of lipid peroxidation. RESULTS: Pretreatment with NO-ASA attenuated dose-dependently gastric erosions provoked by WRS, ischemia-reperfusion, and ethanol. In contrast, ASA aggravated significantly WRS-induced lesions, and this was accompanied by a fall in the GBF, suppression of prostaglandin E(2) generation, and significant rise in ROS chemiluminescence and in plasma TNFalpha and IL-1beta levels. ASA also enhanced significantly the mucosal MDA content and downregulated SOD and GPx mRNA, and these effects were markedly reduced by NO-ASA. CONCLUSION: Coupling of NO to ASA attenuates stress, ischemia-reperfusion, and ethanol-induced damage due to mucosal hyperemia mediated by NO, which compensates for prostaglandin deficiency induced by ASA. ASA aggravates WRS damage via enhancement of ROS and cytokine generation and suppression of SOD and GPx, and these effects are counteracted by NO released from NO-ASA.     

The protective and hormonal effects of proanthocyanidin against gastric mucosal injury in Wistar rats

Background Proanthocyanidin, a grape-seed polyphenol, has been reported to have protective properties against vascular injury and ulcers, preventive effects against atherosclerosis and cancer, and antioxidative effects, such as improving lipid metabolism and slowing aging. However, little has been reported on its antiulcer effects. We aimed to elucidate the antiulcer mechanism of proanthocyanidin.Methods Gravinol, containing 89.3% proanthocyanidin, was used. Proanthocyanidin solution, in distilled water, at 0.002%, 0.02%, 0.2%, or 1%, was given to rats ad libitum for 2 weeks. Distilled water was given to control rats. The effect of proanthocyanidin on gastric mucosal injury was investigated with the water-immersion restraint stress model. The ratios of areas of hemorrhagic erosion were compared as the lesion index. Myeloperoxidase activities were also examined, as an index of tissue injury. Superoxide dismutase activity was measured to examine its antioxidative effect. Furthermore, serum gastrin, somatostatin, histamine, and prostaglandin E₂ levels were measured in this rat model.Results Proanthocyanidin administration significantly suppressed gastric mucosal injury, induced by water-immersion restraint stress, in a dose-dependent manner. Myeloperoxidase activities were also significantly inhibited, whereas superoxide dismutase activities were significantly stimulated. As to gastrointestinal hormones, the secretion of gastrin, somatostatin, and histamine was significantly inhibited, while prostaglandin E₂ secretion was significantly stimulated.Conclusions Proanthocyanidin was shown to have a protective effect on the gastric mucosa. The mechanisms underlying the effect of proanthocyanidin were considered to be the following: anti-gastrin and anti-histamine effects to prevent attacks by water-immersion restraint stress, and mucoprotective properties, bestowed by increased prostaglandin and increased superoxide dismutase activities in the gastric mucosa.     

Role of gastric blood flow, neutrophil infiltration, and mucosal cell proliferation in gastric adaptation to aspirin in the rat.

Gastric mucosa exhibits the ability to adapt to ulcerogenic action of aspirin but the mechanism of this phenomenon is unknown. In this study, acute gastric lesions were produced by single or repeated doses of acidified aspirin in rats with intact or resected salivary glands and with intact or suppressed synthase of nitric oxide. A single oral dose of aspirin produced a dose dependent increase in gastric lesions accompanied by considerable blood neutrophilia and mucosal neutrophil infiltration, significant reduction in gastric blood flow, and almost complete suppression of biosynthesis of prostaglandins. After rechallenge with aspirin, the mucosal damage became smaller and progressively declined with repeated aspirin insults. Gastric adaptation to aspirin was accompanied by a significant rise in gastric blood flow, reduction in both blood neutrophilia and mucosal neutrophil infiltration, and a remarkable increase in mucosal cell regeneration and mucosal content of epidermal growth factor. Salivectomy, which reduced the mucosal content of epidermal growth factor, aggravated the initial mucosal damage induced by the first exposure to acidified aspirin but did not prevent the adaptation of this mucosa to repeated aspirin insults. Pretreatment with NG-nitro-L-arginine (L-NNA), a specific inhibitor of nitric oxide synthase, eliminated the hyperaemic response to repeated aspirin but did not abolish the development of adaptation to aspirin showing that the maintenance of the gastric blood flow plays little part in this adaptation. In conclusion, the stomach adapts readily to repeated aspirin insults and this is accompanied by a considerable reduction in blood neutrophilia and the severity of neutrophil infiltration and by an extensive proliferation of mucosal cells possibly involving epidermal growth factor.     

Interaction of growth hormone-releasing factor and somatostatin on ulcer healing and mucosal growth in rats: role of gastrin and epidermal growth factor

Growth hormone-releasing factor (GRF) was reported to possess the growth-promoting action on the gastroduodenal mucosa that can be augmented by removal of endogenous somatostatin. Since mucosal proliferation was considered to contribute to healing of chronic gastroduodenal ulcerations, we designed the study to determine the interaction of GRF and somatostatin on the healing rate of acetic acid-induced chronic gastric and duodenal ulcers and on the growth of gastroduodenal mucosa in rats. GRF injected subcutaneously twice daily at 100 micrograms/kg/day for 7 days resulted in a significant enhancement of healing rate of both gastric and duodenal ulcerations and this was accompanied by a significant increase in the weight of the mucosa and the contents of RNA and DNA. GRF also significantly increased serum gastrin levels and the tissue contents of epidermal growth factor (EGF) in salivary glands, duodenum and pancreas, suggesting that both gastrin and EGF could contribute to mucosal trophic and ulcer healing effects of GRF. Somatostatin (100 micrograms/kg/day for 7 days) abolished almost completely the ulcer healing and mucosal growth-promoting effects of GRF and this was accompanied by the reduction in serum gastrin level and the tissue contents of EGF suggesting that the suppression of gastrin and EGF release could contribute to the observed effects of somatostatin. We conclude that GRF has both the ulcer healing and the mucosal trophic actions which can be antagonized by somatostatin and that gastrin and EGF may be implicated in these actions.     

Transforming growth factor alpha and epidermal growth factor in protection and healing of gastric mucosal injury.

Transforming growth factor alpha (TGF) and epidermal growth factor (EGF) present in the gastric mucosa are polypeptides with similar biologic activity. This study compares the activity of TGF and EGF in the protection against injury by 100% ethanol and stress and in healing of acute gastric ulcerations. TGF and EGF (12.5-100 micrograms/kg-h) infused subcutaneously 30 min before and during ethanol or stress decreased mucosal lesions dose-dependently. The ID50 for ethanol- and stress-induced lesions after TGF were 40 and 70 micrograms/kg-h and after EGF 60 and 100 micrograms/kg-h. TGF and EGF infused subcutaneously into intact rats inhibited gastric acid secretion but did not affect the gastric blood flow or mucosal generation of prostaglandin E2 (PGE2). Both TGF and EGF also significantly enhanced the healing of stress-induced lesions and the restoration of DNA synthesis. Ethanol and stress reduced blood flow in the oxyntic mucosa by 68% and 51%, respectively, and this effect was partially reversed by EGF and TGF. Pretreatment with indomethacin (5 mg/kg intraperitoneally), which reduced mucosal generation of PGE2 by 85%, decreased in part the protection by TGF and EGF against ethanol-induced damage and virtually abolished the protective action of these peptides against stress-induced injury.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of stress-induced gastric injury in the rat by glutathione

Glutathione metabolism occurs via interorgan cycles in which hepatic synthesis of reduced glutathione and its transfer to extrahepatic tissues play an important role. To elucidate the physiologic significance of the cycles and tissue thiol status during stress-induced gastric mucosal injury, dynamic aspects of glutathione metabolism were analyzed in rats that were treated with water-immersion restraint. This treatment induced gastric mucosal lesion with concomitant decrease in the levels of perchloric acid-soluble thiols in various tissues, particularly in the liver and stomach. During the treatment, glutathione levels markedly decreased in the liver but not in other tissues. Depletion of hepatic glutathione by buthionine sulfoximine, a specific inhibitor for gamma-glutamyl cysteine synthetase, markedly decreased hepatic glutathione levels and increased the gastric injury. Intraperitoneal injection of reduced glutathione significantly increased plasma levels of glutathione and inhibited the occurrence of gastric injury without affecting intracellular glutathione levels. These results indicate that extracellular glutathione and its interorgan metabolism might play a critical role in the protection of gastric mucosa particularly when animals were challenged with various stress.     

Epidermal growth factor,polyamines, and prostaglandins in healing of stress-induced gastric lesions in rats

Previous studies demonstrated that epidermal growth factor (EGF) and polyamines (PA) are capable of protecting gastric mucosa against topical irritants. This study was designed to examine whether EGF, PA, and PG affect the healing of acute gastric lesions induced by water immersion and restraint stress. It was found that the healing process of stress lesions in sham-operated rats was significant after 6 hr after stress, and after 24 hr the number of stress lesions was reduced by about 75%. In sham-operated rats, the healing of ulcerations observed at 6, 12, and 24 hr after the stress was accompanied by gradual restoration of DNA synthesis, and both these processes were significantly reduced by administration of DFMO (an inhibitor of ornithine decarboxylase activity) or indomethacin (an inhibitor of cyclooxygenase). In salivectomized rats, the healing was significantly delayed and the DNA was lowered at all time intervals after the stress. Administration of EGF, spermine, aminoguanidine (an inhibitor of degradation of PA), or 16,16-dmPGE₂ after stress promoted significantly the healing and DNA synthesis, but pretreatment with DFMO abolished the effect of EGF but not that of spermine. We conclude that EGF, PA, and PG are implicated in healing of stress lesions and that EGF acts, at least in part, by the stimulation of PA formation in the gastric mucosa.     

The effect of dexamethasone on gastric mucosal changes following sialoadenectomy in rat

In this study, dexamethasone-induced gastric lesions were studied in rats that had undergone sialoadenectomy. The ultrastructural changes developed during the study were detected by electron microscopically, while blood serum and stomach epidermal growth factor (EGF) concentrations were measured by RIA. The result of the study showed that gastric lesions were correlated with gastric mucus secretion and both serum and mucosa EGF levels. After the administration of dexamethasone, it was found that sialoadenectomy significantly (p<0.01) raised the incidence of stomach lesions (p<0.01), and a significant increase in mucus secretion was also found. Additionally, the serum and gastric mucosal EGF levels fell after sialoadenectomy when compared to normal rats. The most important gastric mucosal changes were observed in rats treated with dexamethasone and those both sialoadenectomised and treated with dexamethasone.     

Day/night differences in stress-induced gastric lesions in rats with an intact pineal gland or after pinealectomy

Abstract:  The formation of acute gastric lesions depends upon the balance between the aggressive factors promoting mucosal damage and the natural defense mechanisms. Previous studies have shown that melatonin inhibits gastric acid secretion, enhances the release of gastrin, augments gastric blood flow (GBF), increases the cyclooxygenase-2 (COX-2)–prostaglandin (PG) system and scavenges free radicals, resulting in the prevention of stress-induced gastric lesions. Besides the pineal gland, melatonin is also generated in large amounts in the gastrointestinal tract and due to its antioxidant and anti-inflammatory properties; this indole might serve as local protective endogen preventing the development of acute gastric damage. The results of the present study indicate that stress-induced gastric lesions show circadian variations with an increase in the day time and a decline at night. These changes are inversely related to plasma melatonin levels. Following pinealectomy, stress-induced gastric mucosal lesions were more pronounced both during the day and at night, and were accompanied by markedly reduced plasma melatonin levels with a pronounced reduction in mucosal generation of prostaglandin E₂ (PGE₂), GBF and increased free radical formation and by small rise in plasma melatonin during the dark phase. We conclude that stress-induced gastric ulcerations exhibit a circadian variation with an increase in the day and attenuation at night and that these fluctuations of gastric stress ulcerogenesis occur also after pinealectomy, depending upon the interaction of COX–PG and free radicals, probably mediated by the changes in local gastric melatonin.     

Effects of water-immersion-induced stress and intraperitoneal administration of brain-gut peptides upon immunoreactive thyrotropin-releasing hormone and prostaglandin E2 concentrations in the rat stomach

The effects of water-immersion-induced stress and intraperitoneal (i.p.) administration of selected neuropeptides on the levels of thyrotropin-releasing hormone (TRH) and prostaglandin E2 (PGE2) were studied in the rat stomach. Water-immersion caused a significant decrease immunoreactive-TRH (ir-TRH) concentrations in the stomach, and a significant increase in ir-TRH concentrations in the gastric juice. The concentrations of PGE2 were significantly increased at 0.5-4 hrs, and significantly decreased at 6-8 hrs after water-immersion. In the experiment of i.p. administration of selected neuropeptides, the level of ir-TRH in the stomach was significantly decreased after VIP injection, whereas it was significantly increased after beta-endorphin injection. The concentration of PGE2 was significantly decreased in the stomach after i.p. administration of TRH and VIP. However, it did not change after beta-endorphin injection. These results indicate that some neuropeptides may participate in regulating the endogenous level of PGE2 and that these interrelations between neuropeptides and PGE2 may be important as ulcerogenic factors in stress ulcers induced by water-immersion in the rat.