Development Of Gastric Mucosal Lesions Research Articles

Preventive effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract on the development of stress-induced acute gastric mucosal lesions in rats

The preventive effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract (TJ-15), a traditional Chinese herbal medicine for the therapies of gastric ulcers and gastritis, on the development of stress-induced acute gastric mucosal lesions was examined in rats with water immersion restraint (WIR) stress. Simultaneous p.o. administration of TJ-15 at a dose of 20, 100 or 250 mg/kg prevented dose-dependently gastric mucosal lesion development in rats subjected to WIR stress over a 6-h period. In the gastric mucosa of rats with WIR stress alone, lipid peroxide concentration and xanthine oxidase (XOD) and myeloperoxidase—an index of neutrophil infiltration—activities increased with lesion development, while nonprotein SH concentration decreased. The simultaneous administration of TJ-15 attenuated all these changes with gastric mucosal lesion development in a dose-dependent manner. These results indicate that simultaneously administered TJ-15 exerts a preventive effect on the development of WIR stress-induced acute gastric lesions in rats, and suggest that the preventive effect of TJ-15 could be due to its preventive actions on enhanced sulfhydryl oxidation and lipid peroxidation via oxygen free radicals generated by the xanthine–xanthine oxidase system and infiltrated neutrophils in the gastric mucosa and on neutrophil infiltration into the tissue.

Modulation of stress-induced gastric mucosal lesions by exogenous L-arginine

L-arginine, a nitric oxide (NO) precursor, can exert both ameriolative and deteriorative effects on gastric mucosal lesions. This study was designed to determine whether exogenous L-arginine modulates stress-induced gastric mucosal lesions through NO production by either constitutive NO synthase (cNOS) or inducible NO synthase (iNOS) in gastric mucosal tissues. In rats subjected to water immersion restraint stress over a 6-hour period, the concentration of gastric mucosal nitrite/nitrate, breakdown products of NO, increased with the development of gastric mucosal lesions and a decrease in cNOS activity and a drastic increase in INOS activity in the gastric mucosal tissue. Preadministration of L-arginine (150 to 600 mg/kg intraperitoneally) attenuated the lesion development with prevention of increases in gastric mucosal nitrite/nitrate concentration and INOS activity. In contrast, postadministration of L-arginine (150 to 600 mg/kg intraperitoneally) enhanced the lesion development with further increase in gastric mucosal nitrite/nitrate concentration. This deteriorative action of postadministration of L-arginine (300 mg/kg intraperitoneally) was prevented by pretreatment with aminoguanidine (100 mg/kg subcutaneously), a selective iNOS inhibitor, with inhibition of increases in gastric mucosal iNOS activity and nitrite/nitrate concentration. These results indicate that preadministered L-arginine protects against water immersion restraint stress-induced gastric mucosal lesions, possibly through restricted NO production by cNOS in gastric mucosal tissues, whereas postadministered L-arginine aggravates the stress-induced gastric mucosal lesions, possibly through excessive NO production by iNOS increasing in gastric mucosal tissues.

ROLE OF ENDOGENOUS SEROTONIN AND HISTAMINE IN THE PATHOGENESIS OF GASTRIC MUCOSAL LESIONS IN UNANAESTHETISED RATS WITH A SINGLE TREATMENT OF COMPOUND 48/80, A MAST CELL DEGRANULATOR

In unanaethetised rats with a single injection of compound 48/80, a mast cell degranulator (0.75 mg kg−1, i.p.), gastric lesions occurred with increased serum serotonin and histamine levels and reduced gastric mucosal blood flow at 0.5 h after the injection and developed at 3 h. Pretreatment with either cyproheptadine (a serotonin and histamine antagonist) or methysergide (a serotonin antagonist) prevented the formation of gastric mucosal lesions with attenuation of reduced gastric mucosal blood flow at 0.5 h after compound 48/80 injection, while pretreatment with either amitriptyline (a selective inhibitor of histamine release from mast cells), tripelennamine (a histamine H1-receptor antagonist), famotidine (a histamine H2-receptor antagonist) or cimetidine (a histamine H2-receptor antagonist) had no effect. Pretreatment with either cyproheptadine, methysergide, amitriptyline or tripelennamine prevented the development of gastric mucosal lesions at 3 h after compound 48/80 injection, while pretreatment with either famotidine or cimetidine had no effect. These results indicate that in unanaesthetised rats with a single compound 48/80 treatment, acutely released endogenous serotonin causes gastric mucosal lesions, while released endogenous histamine mainly contributes to the lesion development and that gastric acid plays little role in the pathogenesis of the compound 48/80-induced acute gastric lesions.

PREVENTIVE EFFECT OF TEPRENONE ON STRESS-INDUCED GASTRIC MUCOSAL LESIONS AND ITS RELATION TO GASTRIC MUCOSAL CONSTITUTIVE NITRIC OXIDE SYNTHASE ACTIVITY

Recently, we demonstrated that teprenone, an anti-ulcer agent, exerts protective and preventive actions against water immersion restraint (WIR) stress-induced gastric mucosal lesions in rats both by inhibiting neutrophil infiltration into the gastric mucosal tissue and by preserving gastric mucus synthesis and secretion. In rats with WIR stress we have also found a decrease in gastric mucosal constitutive nitric oxide synthase (cNOS) activity and a drastic increase in gastric mucosal inducible nitric oxide synthase (iNOS) activity. The decrease in gastric mucosal cNOS activity is closely related to an increase in neutrophil infiltration into the gastric mucosa and a decrease in the level of gastric mucus. In this study of WIR-stressed rats, therefore, we examined whether the inhibitory actions of teprenone on neutrophil infiltration and decreases in mucus synthesis and secretion in the gastric mucosa of rats are related to the change in gastric mucosal cNOS activity during the development of gastric mucosal lesions. Pre-administration of teprenone (200 mg kg−1) prevented the decrease in gastric mucosal cNOS activity with attenuations of neutrophil infiltration into gastric mucosal tissues and decreased levels of gastric mucosal hexosamine, an index of gastric mucin, and adherent mucus in rats with 3 or 6 h of WIR stress. These preventive effects of teprenone on the gastric mucosal neutrophil infiltration and the decrease in gastric mucus levels in rats with WIR stress were completely reversed with inhibition of gastric mucosal cNOS activity by co-administration ofNG-monomethyll-arginine (l-NMMA), a non-selective NOS inhibitor. These results suggest that the inhibitory actions of teprenone on neutrophil infiltration and decreases in mucus synthesis and secretion in the gastric mucosa of rats with WIR stress are closely related to the maintenance of cNOS activity in the gastric mucosal tissue.

NG-nitro- l-arginine methylester is protective against ethanol-induced gastric damage in cholestatic rats

In this study the effect of nitric oxide (NO) synthesis inhibition on ethanol-induced gastric damage was evaluated in bile duct-ligated, sham-operated and unoperated rats. The animals were injected intraperitoneally with saline, l-arginine (200 mg/kg) or N G-nitro- l-arginine methylester ( l-NAME) in doses of 5, 15 and 30 mg/kg, 30 min before ethanol administration. The animals were killed 1 h after ethanol administration and their stomachs were removed for measurement of gastric mucosal damage. The results showed that l-NAME significantly enhanced the development of gastric mucosal lesions in sham-operated and unoperated rats, while in bile duct-ligated animals, l-NAME decreased and l-arginine enhanced the potentiation of ethanol-induced gastric mucosal damage. The plasma level of nitrite and nitrate was also measured and was significantly higher in bile duct-ligated rats than in control groups. The results suggest that inhibition of NO synthase with l-NAME has different effects on ethanol-induced gastric damage in cholestatic groups and in normal rats and that these effects can be explained by overproduction of NO in bile duct-ligated animals.

Participation of xanthine-xanthine oxidase system and neutrophils in development of acute gastric mucosal lesions in rats with a single treatment of compound 48/80, a mast cell degranulator.

The participation of xanthine-xanthine oxidase and neutrophils in the development of acute gastric mucosal lesions was examined in rats injected once with compound 48/80, a mast cell degranulator. Gastric mucosal lesions appeared 0.5 hr after compound 48/80 injection and developed at 3 hr. The formation of gastric mucosal lesions at 0.5 hr after compound 48/80 injection was prevented by pretreatment with anti-neutrophil antiserum and NPC 14686, an antiinflammatory agent, but not with allopurinol, a xanthine oxidase inhibitor. The development of gastric mucosal lesions at 3 hr after compound 48/80 injection was prevented by pretreatment with anti-neutrophil antiserum, NPC 14686, or allopurinol. Increases in the activities of gastric mucosal xanthine oxidase and myeloperoxidase, an index of neutrophil infiltration, and the content of lipid peroxide occurred 0.5 hr after compound 48/80 injection, and these increases were enhanced at 3 hr. The increases in gastric mucosal myeloperoxidase activity and lipid peroxide content at 0.5 hr after compound 48/80 injection were attenuated by pretreatment with anti-neutrophil antiserum and NPC 14686, while only the increase in gastric mucosal xanthine oxidase activity at the same time point was arrested by allopurinol pretreatment. The increases in gastric mucosal xanthine oxidase and myeloperoxidase activities and lipid peroxide content at 3 hr after compound 48/80 treatment were attenuated by pretreatment with anti-neutrophil antiserum, NPC 14686, or allopurinol. When compound 48/80-injected rats were treated with allopurinol at 0.5 hr after compound 48/80 injection, the progression of gastric mucosal lesions at 3 hr after the injection was almost completely prevented with inhibition of the increases in gastric mucosal xanthine oxidase and myeloperoxidase activities and lipid peroxide content. These results indicate that in rats with a single compound 48/80 treatment neutrophils infiltrated into the gastric mucosa participated in the development of acute gastric mucosal lesions and that the xanthine-xanthine oxidase system in the gastric mucosa participated in the progression rather than the formation of the gastric mucosal lesions.

Gastric mucosal damage induced by compound 48/80: roles of serotonin and nitric oxide.

The roles of nitric oxide (NO) and serotonin (5-HT) in the development of gastric mucosal lesions induced by compound 48/80 (48/80) were investigated in rats. Repeated i.p. administration of 48/80 (1 mg/kg) produced damage in the stomach with severe oedema in the submucosa. The lesions induced by 48/80 were prevented by FPL-52694 (a mast cell stabilizer) and methysergide but not tripelennamine. The lesions were also inhibited by simultaneous administration of N(G)-monomethyl-L-arginine (L-NMMA), and this effect was mimicked by inducible NO synthase (iNOS) inhibitors, such as aminoguanidine or dexamethasone and significantly antagonized by coadministration of L-arginine. The mucosal myeloperoxidase activity, thiobarbituric acid reactants and vascular permeability in the stomach were all increased after 48/80 treatment and the changes were also attenuated by cotreatment with L-NMMA. Repeated s.c. treatment with 5-HT (20 mg/kg) provoked similar gastric lesions, which were also prevented by methysergide and iNOS inhibitors, as well as antioxidative drugs, such as allopurinol (a xanthine oxidase inhibitor) and hydroxyurea (a neutrophil-reducing agent). The Ca2 -independent NO synthase (NOS) activity was increased in the gastric mucosa after administration of 48/80 or 5-HT and this change was inhibited by dexamethasone. These results suggest that: (i) the repeated administration of 48/80 induced inflammatory gastric lesions in the rat stomach, mediated by endogenous 5-HT; (ii) NO/iNOS is involved in the pathogenic mechanism of 48/80-induced gastric lesions, in addition to oxyradical formation; and (iii) the deleterious role of NO in this lesion model can be accounted for by a cytotoxic action of peroxynitrite that is formed in the presence of superoxide radicals.

Relation of Inducible Nitric Oxide Synthase Activity to Lipid Peroxidation and Nonprotein Sulfhydryl Oxidation in the Development of Stress-Induced Gastric Mucosal Lesions in Rats

We have reported that increases in lipid peroxide (LPO) formation, nonprotein sulfhydryl (NP-SH) oxidation, and inducible NO synthase (iNOS) activity and a decrease in constitutive NO synthase (cNOS) activity in the gastric mucosa of rats with water immersion restraint (WIR) stress are closely related to gastric mucosal lesion development. Peroxynitrite, which is produced by the reaction of nitric oxide (NO) with superoxide anion, can initiate intracellular LPO formation and NP-SH oxidation, resulting in producing an extreme cellular membrane damage. In this study, the relation of changes in cNOS and iNOS activities to LPO formation and NP-SH oxidation was examined in the gastric mucosa of rats with WIR stress. An increase in iNOS activity, but not a decrease in cNOS activity, correlated well with an increase in LPO concentration (r= 0.750) and NP-SH concentration (r= −0.808) in the gastric mucosa of rats with WIR stress. In addition, the above-mentioned changes in iNOS activity and LPO and NP-SH concentrations with lesion development in the gastric mucosa of rats with WIR stress were attenuated with both prevention of the lesion development and an increase in the concentration of gastric mucosal nitrite/nitrate, the breakdown products of NO, by pretreatment with aminoguanidine, a selective iNOS inhibitor. These results suggest that in the gastric mucosa of WIR-stressed rats, NO produced by increased iNOS could contribute to enhanced LPO formation and NP-SH oxidation, resulting in lesion development.

Protective and preventive effects of teprenone on gastric mucosal lesions in rats

We have reported that neutrophil infiltration into gastric mucosa is closely related to gastric mucosal lesion development in rats with water immersion restraint stress. In this study, we examined the effect of teprenone, which is known to prevent gastric mucosal injury through stimulation of gastric mucus synthesis and secretion, on neutrophil infiltration into the gastric mucosa of rats with water immersion restraint stress. Pre- and post-administration of teprenone (200 mg/kg, p.o.) significantly attenuated the neutrophil infiltration into the gastric mucosa and the lesion development found at 6 h of water immersion restraint stress with preservation of gastric mucosal hexosamine and adherent mucus levels. These results indicate that teprenone exerts protective and preventive actions against water immersion restraint stress-induced gastric mucosal lesions in rats and suggest that these actions could be related to the preservation of gastric mucus synthesis and secretion and inhibition of neutrophil infiltration into the gastric mucosal tissue.

Directin VivoMeasurement of Gastric Microvascular Pressures in the Rat

There are no direct data available on micropressures in the gastric microcirculation in spite of its pivotal role in the development of acute gastric mucosal lesions. Our goal was to develop anin vivomethod to directly measure intravascular pressure and vessel diameter in various gastric microvessels. This paper describes methods and procedural details of our novel preparation of the exteriorized rat stomach for vascular micropuncture studies. The stomach of the anesthetized rat was fixed with minimal surgery in a temperature-controlled gastric chamber. Two preparations were used, both from the serosal side: a seromuscular preparation to study the circulation of superficial outer muscular layers and a submucosal preparation—following careful dissection of the seromuscular layer—to study the submucosal and deeper mucosal microcirculations. Intravascular hydrostatic pressure was measured with a servo-null micropressure measuring system, while vessel diameter was evaluated on the television screen with videometry. Data (average ± SE) were obtained from muscular arterioles (20.8 ± 0.93 μm; 29.8 ± 1.32 mmHg), venules (23.4 ± 1.61 μm; 18.1 ± 0.61 mmHg), submucosal arterioles (50.9 ± 3.55 μm; 55.4 ± 2.78 mmHg), venules (53.7 ± 2.06 μm; 21.4 ± 0.73 mmHg), and deeper mucosal arterioles (20.2 ± 1.06 μm; 33.8 ± 0.81 mmHg), venules (29.9 ± 1.17 μm; 25.8 ± 0.47 mmHg), at a systemic arterial pressure of 110 ± 2.4 mmHg (n= 10 each from 14 animals). Further experiments demonstrated the applicability of this method to examine the effects of systemic blood pressure reduction and local application of vasoactive agents on the gastric microcirculation. This method is useful for analyzing the microcirculation of the stomachin vivounder different experimental conditions.

ROLE OF NITRIC OXIDE IN PATHOGENESIS OF SEROTONINE-INDUCED GASTRIC LESIONS IN RATS

We investigated the role of nitric oxide (NO) in the development of gastric mucosal lesions induced by serotonine (5-HT) in rats. Repeated subcutaneous administration of 5-HT (20 mg kg−1) produced damage in the stomach with severe edema in the submucosa. Gastric lesions induced by 5-HT were prevented by simultaneous administration of aminoguanidine, a selective inducible NO synthase (iNOS) inhibitor, as well as by methysergide, a 5-HT antagonist. In addition, the lesions were inhibited by pretreatment with the antioxidative drugs, such as allopurinol (a xanthine oxidase inhibitor) and hydroxyurea (a neutrophil reducing agent). Following 5-HT treatment, the Ca2+-independent NOS activity in the gastric mucosa was significantly increased within 6 h and remained elevated for 2 days thereafter. The serum NOx levels increased 12 h after the administration of 5-HT, reaching a peak 24 h later. Gastric mucosal thiobarbituric acid (TBA) reactants and myeloperoxidase (MPO) activity were also significantly increased after 2 days treatment with 5-HT. Our results suggest that: (1) the repeated administration of 5-HT induced inflammatory gastric lesions in the rat stomach; (2) iNOS is upreguated during 5-HT treatment, and NO produced by iNOS contributes to development of gastric lesions in response to 5-HT, in addition to the oxyradical formation; and (3) the deleterious role of NO in this model may be accounted for by a cytotoxic action of peroxynitrite that is formed in the presence of NO and superoxide radicals.

Role of Gastric Mucosal Constitutive and Inducible Nitric Oxide Synthases in the Development of Stress-Induced Gastric Mucosal Lesions in Rats

Changes in gastric mucosal constitutive NO synthase (cNOS) and inducible NO synthase (iNOS) activities with the development of gastric mucosal lesions induced by water immersion restraint (WIR) stress were investigated in rats pretreated with and without NOS inhibitors. A decrease in cNOS activity and an increase in iNOS activity in the gastric mucosa occurred with gastric mucosal lesion development. Pretreatment withNG-monomethyl L-arginine, a non-selective NOS inhibitor, enhanced gastric mucosal lesion development with inhibition of gastric mucosal cNOS and iNOS activities, although the inhibited iNOS activity was still higher than the normal level. Pretreatment with aminoguanidine, a selective iNOS inhibitor, prevented gastric mucosal lesion development with inhibition of iNOS activity and maintenance of cNOS activity in the gastric mucosa. These results indicate that in WIR-stressed rats, an increase in iNOS activity and a decrease in cNOS activity in the gastric mucosa are closely related to the development of gastric mucosal lesions.

Suppressed production of nitric oxide as a cause of irregular constriction of gastric venules induced by thermal injury in rats.

Microcirculatory disturbance is a crucial step in development of gastric mucosal lesions. In this study we investigated the influence of nitric oxide (NO) on the irregular constriction of gastric venules observed in rats subjected to thermal injury. Male Wistar rats were anesthetized and a 30% full skin thickness dorsal burn was inflicted. Microvascular images in the submucosal layer and basal region of the gastric mucosa were obtained through an intravital microscope. Distribution of constitutive-type nitric oxide synthase (cNOS) was observed by the immunofluorescence method. Venule walls were basically smooth in the control group (no injury), whereas irregular constrictions tended to be observed in the 5-h group (5 h after thermal injury). Venule diameter was significantly smaller in the 5-h group. In the control group, cNOS-associated fluorescence was found on the venule endothelium, whereas it was almost negligible after thermal injury. A NO donor, 3-morpholinosydnonimine hydrochloride, simultaneously diminished the thermal injury-associated venule constriction and irregularity of venule walls. Therefore, the present study suggests that venule constriction, which is observed 5 h after thermal injury, is related to decreased NO production by endothelial cNOS and is a cause of irregularity of the venule walls.

Disruption of gastric mucosal antioxidant defense system and its relation to the development of gastric mucosal lesions in rats with repeated treatment of compound 48/80, a mast cell degranulator

Abstract The disruption of gastric mucosal antioxidant defense system and its relation to the development of gastric mucosal lesions was examined in Donryu rats treated once daily with compound 48/80 (0.75 mg/kg body weight), a mast cell degranulator, over a four day period. Mucosal lesions appeared after the 1st treatment and developed as the treatment was repeated. Mucosal lipid peroxide levels increased with an increase in the treatment period. Xanthine oxidase activity increased with a decrease in xanthine dehydrogenase activity in the mucosal tissue during the treatment, although the sum of both activities did not change during the treatment. Mucosal myeloperoxidase activity increased with an increase in the treatment period. Mucosal superoxide dismutase activity decreased after the 2nd treatment and a further decrease in activity occurred until the end of the treatment. Mucosal catalase and Se-dependent glutathione peroxidase activities decreased with an increase in the treatment period. A relatively constant decrease in mucosal glutathione reductase activity occurred after the 2nd, 3rd, and 4th treatment. Neither mucosal glucose-6-phosphate dehydrogenase activity nor nonprotein SH content changed during the treatment. A relatively constant decrease in mucosal vitamin E content occurred during the treatment. Mucosal hexosamine content decreased after the 1st treatment. But, mucosal hexosamine content in the compound 48/80-treated rats was equal to the control level after the 2nd treatment and was over the control level after the 3rd and 4th treatment. These results suggest that in rats with repeated compound 48/80-treatment, the disruption of gastric mucosal antioxidant defense system could be related to the development of gastric mucosal lesions.

Stress-induced gastric mucosal lesion and platelet aggregation in rats.

The effect of cold-restraint stress on platelet function in vitro was studied in the rat model. Platelet function was assessed by platelet aggregation in response to adenosine diphosphate (ADP) and thrombin. ADP-induced platelet aggregation was reduced in platelet-rich plasma after 2 h of cold-restraint stress. Thrombin-induced platelet aggregation was reduced with time during cold-restraint stress with a parallel increase in the lesion index. Although pretreatment of animals with atropine prevented the development of gastric mucosal lesions, platelet dysfunction was not reversed by this treatment. These results suggest that cold-restraint stress may impair platelet function, probably due to platelet activation in vivo, and that the abnormalities in platelet function may be associated with the development of gastric mucosal lesions.

Gastric Antisecretory and Antiulcer Actions of Interleukin-1

Increasing evidence suggests that interleukin-1 (IL-1), a cytokine mainly produced by activated monocytes/macrophages, has various biological actions in addition to its immunological activities. In the present study, we examined the effect of IL-1 on gastric secretion and gastric ulcer formation in rats. Gastric secretion was assessed in conscious pylorus-ligated rats weighing approximately 200 g. The peripheral injection of IL-1 resulted in a dose-related inhibition of gastric acid output. The central injection of IL-1 similarly reduced gastric acid secretion at 100 times smaller doses than peripherally injected IL-1, suggesting that this gastric antisecretory action of IL-1 is mediated by the central nervous system. In addition, it was found that this inhibitory effect of IL-1, either peripherally or centrally administered, was still evident at 8 h after injection, indicating the long-lasting property of this IL-1 action. On the basis of these antisecretory actions of IL-1, we determined whether or not pretreatment with IL-1 would prevent experimentally induced gastric ulcer formation. As expected, the central administration of IL-1 dose-dependently suppressed the development of gastric mucosal lesions induced by water-immersion restraint stress, a well-established ulcerogenic procedure. These results clearly demonstrated that IL-1 has potent antisecretory and antiulcer effects that are mediated by the central nervous system. Moreover, these findings suggest that there may exist an "immune-brain-gut" axis, which is involved in the regulation of gastric secretion and mucosal homeostasis, especially under certain pathophysiological conditions that activate the immune system to release various cytokines including IL-1.

Prevention by interleukin-1 of intracisternally injected thyrotropin-releasing hormone (TRH)-induced gastric mucosal lesions in rats

We have recently found that interleukin-1 (IL-1) acts in the central nervous system to potently inhibit gastric acid and pepsin secretion in rats. In the present study, we examined the effects of IL-1 on the development of gastric mucosal lesions induced by intracisternal (i.c.) thyrotropin-releasing hormone (TRH), a neuropeptide known to centrally stimulate gastric secretion. Pretreatment with i.c. injected IL-1 (10 ng/rat) significantly suppressed the severity of TRH-induced gastric erosions. On the other hand, the same dose of i.c. injected IL-1 failed to exert a cytoprotective action for the gastric mucosa against orally administered absolute ethanol. These results suggest that IL-1 has an anti-ulcer effect mainly through its inhibitory action on gastric secretion.

The role of neostigmine in development of acute gastric mucosal lesion in dogs with live bacterial flora-induced shock

The factors that frequently cause the development of acute gastric mucosal lesions (AGML) were studied in 37 mongrel dogs. Bacterial shock was induced by bolus injection of E. coli live bacterial flora (10(10) cells/kg body weight) under parietal cell-stimulated condition by intravenous administration of 0.008 mg/kg per hour of pentagastrin. In addition, 0.01 mg/kg per hour of neostigmine sulfate was administered intravenously during the experiment. Frequent development of AGML was observed in the neostigmine-administered canines without significant changes in the gastric corporal and antral tissue blood flow. In the neostigmine-administered group, AGML was observed in the antrum, although in the other group AGML was mostly observed in the corpus. These results suggest that a neostigmine-induced systemic vagostimulated condition by intravenous administration of neostigmine plays an important role in the development of AGML in dogs subjected to bacterial shock.

The protective effect of vitamin K in bile against the development of gastric mucosal lesions in mice fed a lithogenic diet

The protective effect of vitamin K against the development of gastric mucosal lesions in mice fed a lithogenic diet containing 1% cholesterol and 0.5% cholic acid was studied. The results were as follows: (1) A significantly lower incidence of gastric mucosal lesions was found in mice given subcutaneous injections of 2 mg/kg of vitamin K 1 or K 2 but not in mice given vitamin K 3. (2) Taurocholate in the reflux bile in the stomach may be the major cause of gastric mucosal lesions in mice fed the lithogenic diet. (3) The addition of 0.08 mg/kg of vitamin K to the taurocholate solution, which was topically applied to the gastric mucosa, lowered the incidence of lesions. The protective effect of vitamin K against the development of taurocholate-induced gastric lesions increased with the dosage of the vitamin, but the vitamin's protective effect varied according to the differences in its chemical structure. Vitamin K 1 was the most effective, followed by k 2 and then by K 3. Vitamin K 1 and K 2 were more effective than aluminum hydroxide. It was concluded that the presence of vitamin K in the reflux bile in the stomach has a protective effect against the development of gastric mucosal lesions.

Alternation of Gastric Mucosal Glycoprotein (Lectin-Binding Pattern) in Gastric Mucosa in Stress

Gastric mucosal cells of the rat glandular stomach were studied by light and electron microscopic procedures by use of lectins in the development of acute gastric mucosal lesions. Effects of the H2-receptor antagonist sofalcone (2'carboxymethoxy-4,4'-bis 3-methyl-2) and truncal vagotomy with pyloroplasty on lectin binding sites and distribution were also investigated. Biotinylated lectins in combination with ABC (avidin-biotinyl peroxidase complex) method were used for light and horseradish peroxidase (HRP)-labeled lectins for electron microscopic studies. Gastric mucosal cells showed the specific binding pattern for each lectin by light microscopy. Especially, binding sites and distribution of peanut agglutinin (PNA) were characteristic after induction of stress, truncal vagotomy, and administration of each drug. Staining and distribution increased in the gastric mucosa upward and downward after that. In electron microscopic studies, PNA strongly stained the membranes of the intracellular secretory canaliculi of a parietal cell. These results suggested that alternation of binding sites and distribution was regulated by change of gastric mucosal blood flow and of acidity in the parietal cells. Therefore, increase of glycoconjugate distribution is supposed to be a possibility of cytoprotective effect for a change of environment in the parietal cells.