6-ketoprostaglandin-f1-alpha and Stomach-Ulcer

To investigate the effects of Clostridium butyricum (C. butyricum) on experimental gastric ulcers (GUs) induced by alcohol, restraint cold stress, or pyloric ligation in mice, respectively.. One hundred and twenty mice were randomly allocated into three types of gastric ulcer models (n = 40 each), induced by alcohol, restraint cold stress, or pyloric ligation. In each GU model, 40 mice were allocated into four groups (n = 10 each): the sham control group; model group (GU induction without pretreatment); C. butyricum group (GU induction with C. butyricum pretreatment); and Omeprazole group (GU induction with Omeprazole pretreatment). The effects of C. butyricum were evaluated by examining the histological changes in the gastric mucosal erosion area, the activities of superoxide dismutase (SOD) and catalase (CAT), the level of malondialdehyde (MDA), and the contents of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, leukotriene B4 (LTB4) and 6-keto-PGF-1α (degradation product of PGI2) in the gastric tissue.. Our data showed that C. butyricum significantly reduced the gastric mucosal injury area and ameliorated the pathological conditions of the gastric mucosa. C. butyricum not only minimized the decreases in activity of SOD and CAT, but also reduced the level of MDA in all three GU models used in this study. The accumulation of IL1-β, TNF-α and LBT4 decreased, while 6-keto-PGF-1α increased with pretreatment by C. butyricum in all three GU models.. Our data demonstrated the protective effects of pretreatment with C. butyricum on anti-oxidation and anti-inflammation in different types of GU models in mice. Further studies are needed to explore its potential clinical benefits.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Catalase; Clostridium butyricum; Cold Temperature; Disease Models, Animal; Ethanol; Gastric Mucosa; Gastritis; Inflammation Mediators; Interleukin-1beta; Leukotriene B4; Ligation; Male; Malondialdehyde; Mice, Inbred ICR; Omeprazole; Oxidative Stress; Probiotics; Proton Pump Inhibitors; Pylorus; Restraint, Physical; Stomach Ulcer; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dinoprostone; Immunization; Immunization, Passive; Intestinal Diseases; Male; Stomach Ulcer; Thyroglobulin; Ulcer

To observe the effect of transcutaneous electrical acupoint stimulation(TEAS) of "Zusanli" (ST 36) on gastric mucosal injury in rats with exercise stress-induced gastric ulcer.. Twenty-four SD rats were randomly and equally divided into normal control, model and TEAS groups. Gastric ulcer model was established by forcing the rat to run on a treadmill (15 m/min) till exhaustion, once daily continuously for 15 days. TEAS was applied to bilateral "Zusanli" (ST 36) for 30 min, once daily for 15 days. Behavior changes (crossing and rearing scores) were assessed using open-field test. The ulcer index (UI) of the gastric mucosa was measured by giving the mottling bleeding, streak-like hemorrhage and lesion width with scores according to Guth's method. Contents of 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) and thromboxane B 2 (TXB2) of gastric mucosal tissue were measured using radioimmunoassay.. Compared with the normal group, the levels of crossing and rearing levels in open-field tests, and the duration of forced treadmill running exhaustion, gastromocosal 6-keto-PGF1alpha and TXB2 contents in the model group were obviously reduced (P < 0.01), while the UI of model group was obviously increased (P < 0.01). In comparison with the model group, the scores of crossing and rearing in open-field tests and the duration of forced treadmill running exhaustion and gastromocosal 6-keto-PGF1alpha and TXB2 contents of TEAS group were significantly increased (P < 0.05), and the UI of TEAS group was obviously decreased (P < 0.05).. TEAS of "Zusanli" (ST 36) can protect gastric mucosa from injury in exercise stress-induced gastric ulcer rats.

Topics: 6-Ketoprostaglandin F1 alpha; Acupuncture Points; Animals; Electroacupuncture; Exercise; Gastric Mucosa; Humans; Male; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Stress, Physiological; Thromboxane B2; Transcutaneous Electric Nerve Stimulation

We have previously reported that CGRP plays a critical role in the reduction of stress-induced gastric mucosal injury by increasing gastric prostacyclin (PGI(2)) levels in rats. Estrogen has been shown to increase the production of CGRP in sensory neurons. Isoflavone has estrogen-like effects and is referred to as a phytoestrogen. Thus, we hypothesized that estrogen and isoflavone might inhibit ovariectomy (OVX)-induced decreases in gastric tissue levels of CGRP, thereby attenuating gastric mucosal injury. We examined these possibilities in the present study. The administration of estradiol and isoflavone for 4 wk completely reversed OVX-induced decreases in CGRP mRNA levels of dorsal root ganglion neurons (DRGs) in rats. OVX-induced decreases in gastric tissue levels of CGRP and 6-keto-PGF(1alpha), a stable metabolite of PGI(2), in rats were reversed by estradiol and isoflavone. Water-immersion restraint stress (WIR)-induced increases in gastric tissue levels of CGRP and 6-keto-PGF(1alpha) were inhibited in ovariectomized rats. This inhibition was completely reversed by estradiol and was partially, but significantly, reversed by isoflavone. WIR-induced gastric mucosal injury was exacerbated by OVX, which was reversed by estradiol and isofolavone. In vitro experiments using DRGs isolated from rats demonstrated that neither estradiol nor isoflavone enhanced CGRP release from DRGs, but the former enhanced it in the presence of anandamide, an endogenous agonist for vanilloid receptor-1. These observations suggest that estrogen and isoflavone might inhibit OVX-induced decreases in CGRP levels in DRGs by promoting transcription, thereby contributing to the attenuation of stress-induced gastric mucosal injury in OVX rats.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acids; Calcitonin Gene-Related Peptide; Cannabinoid Receptor Modulators; Cells, Cultured; Endocannabinoids; Enzyme-Linked Immunosorbent Assay; Estradiol; Estrogens; Female; Ganglia, Spinal; Gastric Mucosa; Gene Expression; Isoflavones; Menstrual Cycle; Neurons, Afferent; Ovariectomy; Polyunsaturated Alkamides; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stomach; Stomach Ulcer; Stress, Physiological

Sensory neuron activation reduces water-immersion restraint stress (WIR)-induced gastric mucosal injury by inhibiting neutrophil activation through increase in endothelial production of prostacyclin. This study was designed to examine whether lafutidine, which is an H(2)-receptor antagonist and activates sensory neurons, inhibits neutrophil activation, thereby reducing WIR-induced gastric mucosal injury. Lafutidine enhanced WIR-induced increases in gastric tissue levels of calcitonin gene-related peptide (CGRP) and 6-keto-PGF(1alpha), a stable metabolite of prostacyclin, whereas famotidine, another H(2)-receptor antagonist, did not. Such lafutidine-induced increases in gastric tissue levels of 6-keto-PGF(1alpha) were reversed by pretreatment with capsazepine, an inhibitor of sensory neuron activation, CGRP(8-37), a CGRP antagonist, and indomethacin. Lafutidine inhibited acid-induced exacerbation of gastric mucosal injury in animals subjected to WIR by inhibiting neutrophil activation, whereas famotidine did not. Lafutidine synergistically increased CGRP release from isolated rat dorsal root ganglion neurons in the presence of anandamide, but famotidine did not. These observations suggest that lafutidine might reduce WIR-induced gastric mucosal injury not only by inhibiting acid secretion but also by inhibiting neutrophil activation through enhancement of sensory neuron activation.

Topics: 6-Ketoprostaglandin F1 alpha; Acetamides; Animals; Anti-Ulcer Agents; Arachidonic Acids; Calcitonin Gene-Related Peptide; Capsaicin; Cells, Cultured; Cyclooxygenase Inhibitors; Disease Models, Animal; Endocannabinoids; Famotidine; Ganglia, Spinal; Gastric Acid; Gastric Mucosa; Histamine H2 Antagonists; Indomethacin; Male; Neurons, Afferent; Neutrophil Activation; Peptide Fragments; Piperidines; Polyunsaturated Alkamides; Pyridines; Rats; Rats, Wistar; Restraint, Physical; Stomach Ulcer; Stress, Psychological

Prostaglandins (PGs) and leukotrienes (LTs) are major factors involved in the defense of the gastric mucosa against ulcer formation. However, little is still known about the gastromucosa-protecting action of proton pump inhibitors (PPIs) and histamine H(2) receptor antagonists (H(2) blockers) in patients with gastric ulcer. We therefore examined the effectiveness of a PPI in protecting the gastric mucosa.. We compared the PGE(2) and LTB(4) levels and the expression levels of cyclooxygenase (COX)-1 and COX-2 mRNA in the gastric mucosa in gastric ulcer patients between the group treated for 8 weeks with a PPI, rabeprazole (PPI group; n=5), and the group treated for 8 weeks with an H(2) blocker, ranitidine (H(2) blocker group; n=6), as well as in nonulcer subjects (control group; n=5).. The mucosal levels of PGE(2) and COX-2 mRNA expression were significantly lower in the ulcer patients than those in the nonulcer patients, whereas the LTB(4) level was significantly higher in the ulcer patients than that in the nonulcer patients, and it was also significantly lower in the ulcerated mucosa than that in the nonulcerated mucosa. The PPI group had a significantly increased PGE(2) and decreased LTB(4) levels in comparison to the H(2) blocker group during the ulcer-healing stage. The COX-1 mRNA expression showed no difference among the PPI and H(2) blocker groups or between before and after the treatment. However, the COX-2 mRNA expression increased in the PPI group more than that in the H(2) blocker group during the ulcer-healing stage.. These findings demonstrated the significant gastric-mucosa-protecting effect of PPI by increasing the PGE(2) production and reducing the LTB(4) production.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; 6-Ketoprostaglandin F1 alpha; Adult; Aged; Cyclooxygenase 2; Dinoprostone; Female; Gastric Mucosa; Humans; Leukotriene B4; Male; Middle Aged; Rabeprazole; Ranitidine; RNA, Messenger; Stomach Ulcer

To investigate the protective mechanisms of Weikang (WK) decoction on gastric mucosae.. Ninety rats were randomly divided into nine groups of 10 each, namely group, model group, group with large WK dosage, group with medium WK dosage, group with small WK dosage, group with herbs of jianpiyiqi (strengthening the spleen and replenishing qi), group with herbs of yangxuehuoxue (invigorating the circulation of and nourishing the blood), group with herbs of qingrejiedu (clearing away the heat-evils and toxic materials), group with colloidal bismuth pectin (CBP) capsules. According to the method adopted by Yang Xuesong, except normal control group, chronic gastric ulcer was induced with 100% acetic acid. On the sixth day after moldmaking, WK decoction was administered, respectively at doses of 20, 10 and 5 g/kg to rats of the WK groups, or the groups with herbs of jianpiyiqi, yangxuehuoxue and qingrejiedu, 10 mL/kg was separately administered to each group every day. For the group with CBP capsules, medicine was dissolved with water and doses 15 times of human therapeutic dose were administered (10 mL/kg solution containing 0.35% CBP). Rats of other groups were fed with physiological saline (10 mL/kg every day). Administration lasted for 16 d. Rats were killed on d 22 after mold making to observe changes of gastric mucosa. The mucus thickness of gastric mucosa surface was measured. Levels of epidermal growth factor (EGF) in gastric juice, nitric oxide (NO) in gastric tissue, endothelin (ET) in plasma, superoxide dismutase (SOD) in plasma, malondialdehyde (MDA) in plasma and prostaglandin I(2) (PGI(2)) were examined.. Compared with control group, ulceration was found in gastric mucosa of model group rats. The mucus thickness of gastric mucosa surface, the levels of EGF, NO, 6-K-PGF(1)alpha and SOD decreased significantly in the model group (EGF: 0.818+/-0.18 vs 2.168+/-0.375, NO: 0.213+/-0.049 vs 0.601+/-0.081, 6-K-PGF(1)alpha: 59.7+/-6.3 vs 96.6+/-8.30, SOD: 128.6+/-15.0 vs 196.6+/-35.3, P<0.01), the levels of ET (179.96+/-37.40 vs 46.64+/-21.20, P<0.01) and MDA (48.2+/-4.5 vs 15.7+/-4.8, P<0.01) increased. Compared with model group, the thickness of regenerative mucosa increased, glandular arrangement was in order, and cystic dilative glands decreased, while the mucus thickness of gastric mucosa surface increased (20 g/kg WK: 51.3+/-2.9 vs 23.2+/-8.4, 10 g/kg WK: 43.3+/-2.9 vs 23.2+/-8.4, 5 g/kg WK: 36.1+/-7.2 vs 23.2+/-8.4, jianpiyiqi: 35.4+/-5.6 vs 23.2+/-8.4, yangxuehuoxue: 33.1+/-8.9 vs 23.2+/-8.4, qingrejiedu: 31.0+/-8.0 vs 23.2+/-8.4 and CBP: 38.2+/-3.5 vs 23.2+/-8.4, P<0.05-0.01). The levels of EGF (20 g/kg WK: 1.364+/-0.12 vs 0.818+/-0.18, 10 g/kg WK: 1.359+/-0.24 vs 0.818+/-0.18, 5 g/kg WK: 1.245+/-0.31 vs 0.818+/-0.18, jianpiyiqi: 1.025+/- 0.45 vs 0.818+/-0.18, yangxuehuoxue: 1.03+/-0.29 vs 0.818+/-0.18, qingrejiedu: 1.02+/-0.47 vs 0.818+/-0.18 and CBP: 1.237+/-0.20 vs 0.818+/-0.18, P<0.05-0.01), NO (20 g/kg WK: 0.480+/-0.026 vs 0.213+/-0.049, 10 g/kg WK: 0.390+/-0.055 vs 0.213+/-0.049, 5 g/kg WK: 0.394+/-0.026 vs 0.213+/-0.049, jianpiyiqi: 0.393+/-0.123 vs 0.213+/-0.049, yangxuehuoxue: 0.463+/-0.077 vs 0.213+/-0.049, qingrejiedu: 0.382+/-0.082 vs 0.213+/-0.049 and CBP: 0.395+/-0.053 vs 0.213+/-0.049, P<0.05-0.01), 6-K-PGF(1)alpha (20 g/kg WK: 86.8+/-7.6 vs 59.7+/-6.3, 10 g/kg WK: 77.9+/-7.0 vs 59.7+/-6.3, 5 g/kg WK: 70.0+/-5.4 vs 59.7+/-6.3, jianpiyiqi: 73.5+/-12.2 vs 59.7+/-6.3, yangxuehuoxue: 65.1+/-5.3 vs 59.7+/-6.3, qingrejiedu: 76.9+/-14.6 vs 59.7+/-6.3, and CBP: 93.7+/-10.7 vs 59.7+/-6.3, P<0.05-0.01) and SOD (20 g/kg WK: 186.4+/-19.9 vs 128.6+/-15.0, 10 g/kg WK: 168.2+/-21.7 vs 128.6+/-15.0, 5 g/kg WK: 155.6+/-21.6 vs 128.6+/-15.0, jianpiyiqi: 168.0+/-85.3 vs 128.6+/-15.0, yangxuehuoxue: 165.0+/-34.0 vs 128.6+/-15.0, qingrejiedu: 168.2+/-24.9 vs 128.6+/-15.0, and CBP: 156.3+/-18.1 vs 128.6+/-15.0, P<0.05-0.01) significantly increased. The levels of ET (20 g/kg WK: 81.30+/-17.20 vs 179.96+/-37.40, 10 g/kg WK: 83.40+/-25.90 vs 179.96+/-37.40, 5 g/kg WK: 93.87+/-20.70 vs 179.96+/-37.40, jianpiyiqi: 130.67+/-43.66 vs 179.96+/-37.40, yangxuehuoxue: 115.8. WK decoction and separated recipes have significantly protective effect on ethanol-induced gastric mucosal injury. They can increase the content of EGF in gastric juice, PGI(2) SOD in plasma and NO in gastric tissues, thicken the mucus on the gastric mucosa, and decrease the impairing factor MDA, ET in plasma.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Drugs, Chinese Herbal; Endothelins; Epidermal Growth Factor; Female; Gastric Juice; Gastric Mucosa; Male; Malondialdehyde; Nitric Oxide; Rats; Rats, Wistar; Stomach Ulcer; Superoxide Dismutase

To assess the synergistic action of famotidine (FMD) and chlorpheniramine (CPA) on acetic acid-induced chronic gastric ulcer in rats.. Chronic gastric lesions were induced in male Sprague-Dawley (SD) rats by serosal application of the acetic acid. Forty SD rats were randomly divided into blank group (n = 8), control group (n = 8), FMD group (n = 8), CPA group (n = 8), and FMD+CPA group (n = 8). Each group was given intraperitoneally (i.p.) 0.5 mL/100 g distilled water, 9 g/L NaCl saline, 4 mg/kg FMD, 10 mg/kg CPA, 4 mg/kg FMD+10 mg/kg CPA, respectively, daily for 10 d. On d 10, ulcer area was determined by planimetry. The level of myeloperoxidase (MPO) in the liver homogenization was determined by biochemical methods and the plasma levels of 6-ketoprostaglandin F1 alpha (6-keto-PGF(1a)) and IL-8 were determined by radioimmunoassay.. The synergistic effects of FMD+CPA group on the lesion, IL-8, 6-keto-PGF(1a) and MPO were confirmed. The effect of FMD+CPA group was significantly different as compared to the control and FMD groups. The lesion (mm(2)) was reduced from 40.18+/-2.6 in control group to 6.83+/-2.97 in PMD+CPA group, P<0.01, and from 32.9+/-3.27 in FMD group to 6.83+/-2.97 in PMD+CPA group, P<0.01. The plasma levels of IL-8 decreased from 0.69+/-0.11 ng/L in control group to 0.4+/-0.04 ng/L in PMD+CPA group, P<0.01, and from 0.51+/-0.08 ng/L in FMD group to 0.4+/-0.04 ng/L in PMD+CPA group, P<0.05. The level of 6-keto-PGF(1a) increased from 7.55+/-1.65 ng/L in control group to 16.62+/-0.97 ng/L in PMD+CPA group, P<0.01, and from 13.15+/-1.48 ng/L in FMD group to 16.62+/-0.97 ng/L in PMD+CPA group, P<0.05. The levels of MPO in the liver homogenate decreased from 9.12+/-2.05 u/L in control group to 4.33+/-0.95 u/L in PMD+CPA group, P<0.01, and from 8.3+/-1.29 u/L in FMD group to 4.33+/-0.95 u/L, P<0.01.. The synergistic action of FMD and CPA on acetic acid-induced chronic gastric ulcer in rats decreases the incidence of ulcer and also enhances the healing of ulcer.

Topics: 6-Ketoprostaglandin F1 alpha; Acetic Acid; Animals; Chlorpheniramine; Chronic Disease; Drug Synergism; Famotidine; Histamine H1 Antagonists; Histamine H2 Antagonists; Interleukin-8; Liver; Male; Peroxidase; Rats; Rats, Sprague-Dawley; Stomach Ulcer

The phenomenon by which the gastric mucosa is protected in response to mild irritants has been called adaptive cytoprotection, a mechanism believed to be related to production of endogenous prostaglandins (PGs). We tested whether PGs generated by mild irritant prevent injury through the release of calcitonin gene-related peptide (CGRP) from the sensory nerves using prostanoid receptor-knockout mice.. The stomach was doubly cannulated and perfused with 1 mol/L NaCl or 50% ethanol. CGRP levels in the perfusate were determined by enzyme immunoassay, and the injured area was estimated at the end of perfusion.. Preperfusion with mildly hypertonic saline (1 mol/L NaCl) increased generation of gastric PGE(2) and PGI(2) and reduced ethanol-induced mucosal damage. Exposure of ethanol after 1 mol/L NaCl increased intragastric CGRP levels from 166 +/- 27 to 713 +/- 55 pg/2 min (n = 4, P < 0.05), and the protective action of 1 mol/L NaCl was inhibited by indomethacin treatment. CGRP antagonist blocked 1 mol/L NaCl-induced protective effect. Intragastric perfusion of 50% ethanol after administration of PGI(2), but not of PGE(2), increased CGRP levels. Application of 1 mol/L NaCl to IP receptor-knockout mice (IP(-/-)) did not elicit the protective effects seen in the wild-type on ethanol-induced gastric mucosal lesions. Protective effect of 1 mol/L NaCl was observed in EP3 receptor-knockout mice (EP3(-/-)). CGRP level during ethanol perfusion was not increased in IP(-/-) but was increased in EP3(-/-) and wild-type counterparts after preperfusion of 1 mol/L NaCl.. These results indicate that the endogenous PGI(2) generated by 1 mol/L NaCl may have a protective role in gastric mucosal injury through enhancement of CGRP release from gastric mucosa. This mechanism may explain the adaptive cytoprotection observed after treatment with mild irritants.

Topics: 6-Ketoprostaglandin F1 alpha; Adaptation, Physiological; Anesthesia; Animals; Anti-Inflammatory Agents, Non-Steroidal; Calcitonin Gene-Related Peptide; Central Nervous System Depressants; Dinoprostone; Epoprostenol; Ethanol; Gastric Mucosa; Indomethacin; Male; Mice; Mice, Knockout; Neurons, Afferent; Peptide Fragments; Rats; Rats, Sprague-Dawley; Receptors, Epoprostenol; Receptors, Prostaglandin; Sodium Chloride; Stomach Ulcer

The anti-inflammatory and ulcerogenic effects of FR188582, 3-chloro-5-[4-(methylsulfonyl) phenyl]-1-phenyl-1H-pyrazole, were investigated. In a recombinant human cyclooxygenase (COX) enzyme activity, FR188582 inhibited COX-2 with an IC50 value of 0.017 microM, and the inhibition of prostaglandin (PG) E2 formation by FR188582 was over 6000 times more selective for COX-2 than COX-1. Oral administration of FR188582 dose-dependently inhibited adjuvant arthritis. This effect was threefold more potent than that of indomethacin. FR188582 and indomethacin dose-dependently suppressed the formation of immunoreactive PGE2, but not immunoreactive leukotriene (LT) B4, in arthritic paw. Unlike indomethacin, FR188582 did not induce visible gastric lesions in rats at doses up to 32 mg/kg, p.o. Furthermore, FR188582 did not inhibit the level of immunoreactive PGE2 and immunoreactive 6-keto PGF1alpha in rat gastric mucosa. These results suggest that FR188582, a highly selective COX-2 inhibitor, has a potent anti-inflammatory effect mediated by inhibition of PGE2 in inflamed tissues. The safety profile of FR188582 appears to be improved over the safety profile of indomethacin.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; CHO Cells; Cricetinae; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Female; Gastric Mucosa; Humans; Indomethacin; Isoenzymes; Leukotriene B4; Membrane Proteins; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Rats; Rats, Inbred Lew; Recombinant Proteins; Stomach Ulcer

The interaction of antithrombin (AT) with cell surface glycosaminoglycans has been shown to promote the endothelial release of prostacyclin (PGI2). Because PGI2 plays an important role in gastric cytoprotection, we examined whether AT prevents water-immersion restraint stress (WIR)-induced gastric mucosal injury in rats by promoting the endothelial release of PGI2. Intravenous administration of AT (250 U/kg) prevented WIR-induced gastric mucosal injury in rats. Gastric levels of 6-keto-prostaglandin F1alpha, a stable metabolite of PGI2, were significantly increased 0.5 and 1 hour after WIR in animals administered AT compared with control animals. The effects induced by AT in animals subjected to WIR were not observed in animals that were administered DEGR-Xa, a selective inhibitor of thrombin generation, or Trp49-modified AT, which lacks affinity for heparin. In animals subjected to WIR gastric mucosal blood flow was significantly reduced with a simultaneous increase in gastric mucosal microvascular permeability. Activated neutrophils have been implicated in the WIR-induced reduction of gastric mucosal blood flow by increasing microvascular permeability. Although AT prevented the reduction of gastric mucosal blood flow and the increase in gastric mucosal microvascular permeability in animals subjected to WIR, neither DEGR-Xa nor Trp49-modified AT had any effect. Pretreatment of animals with indomethacin completely inhibited the protective effects of AT against WIR-induced gastric mucosal injury and the AT-induced increase in post-WIR gastric 6-keto-prostaglandin F1alpha levels. These results strongly suggest that AT prevents stress-induced gastric mucosal injury by increasing the gastric levels of PGI2 through the interaction of AT with cell-surface glycosaminoglycans, thus increasing gastric mucosal blood flow both by vasodilation and by inhibiting neutrophil activation.

Topics: 6-Ketoprostaglandin F1 alpha; Albumins; Amino Acid Chloromethyl Ketones; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antithrombins; Epoprostenol; Factor Xa; Fibrin; Fibrinogen; Gastric Mucosa; Immersion; Indomethacin; Male; Peroxidase; Rats; Rats, Wistar; Regional Blood Flow; Stomach Ulcer; Stress, Physiological; Time Factors; Tryptophan

Systemic administration of capsaicin aggravates ethanol-induced injury of rat gastric mucosa. We evaluated the effect of subcutaneous administration of capsaicin on the gastric mucosa and on inflammatory mediators in saline- and ethanol-treated rats. Functional ablation of primary afferent C-fibers by capsaicin (total 100 mg/kg subcutaneous) tripled ethanol-induced damage. Pretreatment with ketotifen, a mast cell stabilizer (1 mg/kg) protected rat gastric mucosa from the amplified injury induced by capsaicin and ethanol. Tempol, a selective nontoxic cell-permeable nitroxide, completely prevented the amplified gastric ulceration induced by capsaicin and ethanol. This was accompanied by a significant decrease in leukotriene B4 and C4 generation. It is therefore suggested that mast cells and free radicals contribute to the amplified injury observed in rats pretreated with capsaicin and ethanol and that the pharmacological modulation of mast cell release and scavenging of free radicals may be of therapeutic efficacy in the prevention of gastric injury.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Capsaicin; Cyclic N-Oxides; Ethanol; Free Radical Scavengers; Free Radicals; Gastric Mucosa; Ketotifen; Leukotriene B4; Leukotriene C4; Male; Mast Cells; Nerve Fibers; Platelet Activating Factor; Premedication; Protein Synthesis Inhibitors; Rats; Rats, Sprague-Dawley; Spin Labels; Stomach Ulcer

The anti-ulcer effects of bifidobacteria, lactobacilli and streptococci were examined using the acetic acid-induced gastric ulcer and ethanol-induced erosion models in rats. Bifidobacterium breve YIT4014 and 4043, and Bifidobacterium bifidum YIT4007 were administered orally, and anti-ulcer effects were confirmed for not only these organisms but also their polysaccharide fractions (PSFs). The major component of these anti-ulcer polysaccharides was rhamnose. In particular, polysaccharides in which the rhamnose content exceeded 60% were more effective in healing gastric ulcers. After administration of the PSF from B. bifidum YIT4007, the levels of epidermal growth factor and basic fibroblast growth factor increased in gastric tissues. Similar results were observed for the culture supernatant of gastric epithelial cells cultured with PSF. Furthermore, the production of 6-ketoprostaglandin F1 alpha by macrophages was also enhanced by PSF. These results indicated that these bacteria and their polysaccharides induced host repair and protective systems in the gastric ulcer model.

Topics: 6-Ketoprostaglandin F1 alpha; Acetates; Animals; Anti-Ulcer Agents; Bifidobacterium; Cell Wall; Epidermal Growth Factor; Ethanol; Gastric Mucosa; Macrophages; Male; Polysaccharides, Bacterial; Rats; Rats, Sprague-Dawley; Stomach Ulcer

In the present study, the role of endogenous prostanoid synthesis in gastric mucosa in the healing of chronic gastric ulcers was investigated. Nineteen patients were divided into two groups in accordance with healing state after one month of treatment with cimetidine only: "healed group" and "unhealed group". Biopsy specimens taken from the mucosa around the ulceration (damaged gastric mucosa) and at a distance from the ulceration (normal gastric mucosa) at endoscopy prior to treatment were homogenized, and the mucosal prostanoid synthesis was determined using [14C]arachidonic acid. The mean value of prostaglandin E2 synthesis in the normal gastric mucosa of the healed group was 60% higher than in that of the unhealed group, but the difference was not significant. However, prostaglandin E2 synthesis in the damaged gastric mucosa of the healed group was 117% higher than in that of the unhealed group. The same tendency was observed for prostaglandin D2 and 6-keto prostaglandin F1 alpha synthesis as for prostaglandin E2. In our study it was demonstrated that there is a good correlation of prostaglandin synthesis in the damaged mucosa with healing of chronic gastric ulceration. Furthermore, our study indicated that prostaglandin synthesis, especially in damaged mucosa, might be important in the healing of gastric ulceration.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Autoradiography; Chronic Disease; Cimetidine; Dinoprostone; Female; Gastric Mucosa; Humans; Male; Middle Aged; Prostaglandin D2; Prostaglandins; Stomach Ulcer

According earlier, investigations nitrogen bridgehead compounds make a representative group of non-prostaglandin type gastroprotective agents. One member of this group is CHINOIN-127 (1,6-dimethyl-4-oxo-1, 6, 7, 8, 9, 9a-hexahydro-4H-pyrido-(1, 2a)-pyrimidine-3-carbox-amide). CHINOIN-127 is a potent non-narcotic analgesic and antiinflammatory agent and has a remarkable protective effect on indomethacin induced ulcer (ED50 = 25 mg/kg p.o.) and on acidified ethanol induced ulcer (ED50 = 26 mg/kg p.o.). In this study we examined the mechanism of action of cytoprotective effect of this drug and we made a comparison between the cytoprotective effect of 20% ethanol and 25 mg/kg CHINOIN-127. In the gastric mucosa of control rats we observed a balance between TxA2 and PGI2 (PGI2/TxA2 = 3.8) and between the cytoprotective prostaglandins (PGI2 and PGE2) and ulcerogen eicosanoids (TxA2 and leukotrienes) (PGI2 + PGE2/TxA2 + LTs = 3.9). 100% ethanol treatment causes disintegration of this balance, shifting the synthesis towards the ulcerogen eicosanoids production. CHINOIN-127 and 20% ethanol pretreatment improves the deranged balance between cytoprotective prostaglandins and ulcerogen eicosanoids. Our results demonstrate that CHINOIN-127 and 20% ethanol have a similar mechanism of cytoprotective action on ethanol induced ulcer in rats.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Epoprostenol; Ethanol; Gastric Mucosa; Pyrimidinones; Rats; Rats, Wistar; Stomach Ulcer; Thromboxane B2

Prostaglandin E2 (PGE2)- and 6-keto-PGF1 alpha-like immunoactivity was measured in incubates of forestomach and gastric corpus mucosa in (a) unoperated rats, (b) rats with sham-operation of the kidneys and (c) rats with bilateral nephrectomy. In addition the mean ulcer area in the forestomach and gastric mucosa was assayed in all three groups of rats. The PGE2- and 6-keto-PGF1 alpha-like immunoactivity in gastric mucosa incubates and 6-keto-PGF1 alpha in the forestomach incubates was almost the same in unoperated and sham-operated rats. Increased 6-keto-PGF1 alpha in the forestomach and of PGE2 and 6-keto-PGF1 alpha in the gastric mucosa was found in rats with bilateral nephrectomy before gastric lesions were seen. A higher mean ulcer area occurred in the forestomach and gastric mucosa 24-48 h after bilateral nephrectomy. We conclude, that the increased PGE2- and 6-keto-PGF1 alpha production by the gastric mucosa and forestomach was associated with the loss of normal renal tissue function. Despite the protection of PGE2 and PGI2 by gastric tissue, gastric lesions nevertheless occur in acute uraemic rats.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dinoprostone; Female; Gastric Mucosa; Immunoassay; Kidney; Nephrectomy; Rats; Rats, Wistar; Stomach Ulcer

To determine the effect of different doses of hydrocortisone sodium succinate (HC) on rat gastric mucosal prostaglandin synthesis, two experiments were performed. In the first experiment, 20 male Lewis rats were divided into 4 groups of 5 rats each and gavaged either with 2 ml of water (control) or different concentrations of HC (10 mg/ml, 100 mg/ml and 500 mg/ml). In the second experiment in a similar design, lower doses of HC were used (water, 0.1 mg/ml, 0.50 mg/ml and 5.0 mg/ml). The rats were killed after 1 h and three 3 x 3 mm pieces of gastric tissue were removed from each rat and incubated for the determination of prostaglandin E2 and 6-keto-prostaglandin F1 alpha accumulation in the medium measured by radioimmunoassay. At low doses HC inhibits rat gastric mucosal prostaglandin synthesis whereas at higher doses HC stimulates it. This biphasic effect of HC on gastric mucosal prostaglandin synthesis may help explain its role in ulcerogenesis.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dinoprostone; Dose-Response Relationship, Drug; Gastric Mucosa; Hydrocortisone; Male; Prostaglandins; Rats; Rats, Inbred Lew; Stomach Ulcer

N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl (DPPE) is an antihistamine with a unique profile of activity in the stomach. It is antisecretory and blocks the formation of experimental cold/stress- and ethanol-induced gastric lesions, as well as cysteamine-induced duodenal ulcers in a fashion more potent than observed with histamine H2 antagonists such as cimetidine. We now demonstrate that the antiulcer effects of DPPE are associated with a dramatic (10-fold) rise in the stable prostacyclin hydration product 6-keto-prostaglandin F1 alpha in gastric secretion collected from conscious rats. Cyclooxygenase inhibitors such as acetylsalicylic acid, indomethacin and sodium meclofenamate abolish high-dose DPPE-induced gastroprotection, whereas sodium salicylate, a lipoxygenase inhibitor, does not. These data suggest that DPPE-induced gastroprotection is mediated, at least in part, through an increase in endogenous prostacyclin (prostaglandin I2) synthesis in the gastric mucosa. These data are not consistent with an effect of DPPE primarily at the H2 receptor, but are consistent with the recent suggestion that DPPE antagonizes histamine at HIC, an intracellular histamine site.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Ulcer Agents; Epoprostenol; Gastric Juice; Gastric Mucosa; Histamine Antagonists; Male; Phenyl Ethers; Rats; Rats, Inbred Strains; Stomach Ulcer; Stress, Physiological

Experiments performed in animals and in healthy human subjects suggest that antacids increase prostaglandin synthesis and have a cytoprotective effect on gastroduodenal mucosa. To investigate this hypothesis, the ability was evaluated of an antacid containing an aluminium/magnesium hydroxide combination (Maalox TC) to modify prostanoid production at the gastric level in 28 patients with gastric antral ulcer of various sizes in different stages of activity with or without erosive gastritis. After the antacid treatment, a significant prostaglandin E2 reduction was observed, together with a significant 6-keto-prostaglandin F1 alpha increase, but there was no thromboxane B2 variation at antrum level, nor any significant modification of prostanoid production at body level. The decreased prostaglandin E2 levels, detected after treatment with the antacid combination, may be due to lesion improvement, decreased synthesis or increased catabolism by mucosal cells, to a drop in this prostaglandin production by inflammatory cells. As far as 6-keto-prostaglandin F1 alpha is concerned, the obtained data confirm the results reported by other authors in healthy human subjects. The increase of this prostaglandin could enhance blood flow, resulting in a protective effect.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aluminum Hydroxide; Antacids; Dinoprostone; Drug Combinations; Gastric Mucosa; Humans; Magnesium Hydroxide; Middle Aged; Stomach Ulcer

During Shay-ulcer formation damages to the barrier of the gastric mucosa develop even before the appearance of macroscopic ulceration. Proximal selective vagotomy prevents these damages. Following pyloric ligation the prostaglandin content of the mucosa changes in parallel with the injuries of the mucosal barrier: TXB2 content of the forestomach increases, while PGF2 alpha content of both the forestomach and the antrum decreases. Following PSV operation the 6-keto-PGF1 alpha content of the mucosa decreases, whereas PGF2 alpha and TXB2 contents exhibit no alteration. As a combined effect of proximal selective vagotomy pretreatment and pyloric ligation the 6-keto-PGF1 alpha and PGF2 alpha contents of the mucosa remain low and the TXB2 increase, otherwise detectable after pyloric ligation, does not take place.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dinoprost; Disease Models, Animal; Gastric Mucosa; Prostaglandins; Pyloric Antrum; Radioimmunoassay; Rats; Stomach Ulcer; Thromboxane B2; Vagotomy, Proximal Gastric

German Giant rabbits successfully immunized against prostaglandin (PG) E2 as shown by a rise in antibody titers developed gastric mucosal lesions. Enzymatically dispersed gastric mucosal cells of these animals had a significantly enhanced production of PG E2 and PG I2 as measured by specific radioimmunoassays. This may be explained by an increased supply with endogenous arachidonic acid (as indicated by an enhanced phospholipase A2/LAT ratio) and by a higher activity of the subsequent PG forming enzymes (as indicated by a more effective stimulation of PG production by exogenous arachidonic acid). Gastric mucosal plasma membranes of immunized rabbits had significantly higher PG E2 binding capacity (108 +/- 9 fmol/mg protein) than those of nonimmunized rabbits (72 +/- 5 fmol/mg protein). The ligand affinity was not affected by immunization. Neither histamine-stimulated 14C-amino-pyrine uptake of isolated parietal cells as a marker for acid production nor its inhibition by PG E2 were influenced by receptor up-regulation. The increased eicosanoid release can be regarded as an endogenous defense mechanism against increased mucosal vulnerability caused by PG E2 scavenging. The potential role of PG E2 receptor up-regulation in support of this process remains to be established.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Antibody Formation; Arachidonic Acids; Dinoprostone; Epoprostenol; Gastric Acid; Gastric Mucosa; Indomethacin; Lysophosphatidylcholines; Male; Parietal Cells, Gastric; Phospholipases A; Phospholipases A2; Rabbits; Receptors, Prostaglandin; Stomach Ulcer

Mucosa damage, these appear in the Shay ulcer model before the macroscopic ulceration, can be prevented by the selective proximal vagotomy. Changes of the potential difference and the prostaglandin content were discovered after pylorus ligation, and Thromboxane was increased, PGF2 alpha and TXB2 were nearly constant, whereas 6-keto-PGF1 alpha increased clearly in the rumen. The 6-keto-PGF1 alpha and the PGF2 alpha content and Thromboxane remained unchanged and the potential difference was normalized in case of selective proximal vagotomy and pylorus ligation. The SPV is significant as you know for the secretion of H+ion and bicarbonate, but also for the normalization of increased TXB2 on the basis of our investigation results.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dinoprost; Disease Models, Animal; Gastric Mucosa; Male; Prostaglandins; Rats; Stomach Ulcer; Thromboxane B2; Thromboxanes; Vagotomy, Proximal Gastric

Fundic mucosal content and synthesis of 6-ketoprostaglandin F1 alpha, the major prostanoid in the rat gastric mucosa, were determined after rats had ingested a diet containing 10% fish oil or 10% corn oil for 4 wk. 6-Ketoprostaglandin F1 alpha content and synthesis in rats fed a fish oil-supplemented diet were reduced significantly compared with rats receiving a corn oil-supplemented diet (P less than 0.05). However, rats receiving 10% fish oil for 8 wk sustained significantly less gastric mucosal injury after intragastric challenge with 15% and then with absolute ethanol than rats receiving 10% corn oil or regular chow for 8 wk (P less than 0.05). Thus fish oil ingestion protected the gastric mucosa even though fish oils reduced mucosal prostaglandin synthesis.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Ethanol; Female; Fish Oils; Gastric Mucosa; Indomethacin; Rats; Rats, Inbred Strains; Stomach Ulcer; Weight Gain

Active immunization of rabbits with a 6-ketoprostaglandin F1 alpha-thyroglobulin conjugate induced gastrointestinal ulceration, whereas active immunization of rabbits with 13,14-dihydro-15-keto prostaglandin E2-thyroglobulin conjugate or with thyroglobulin alone did not result in ulceration. Passive immunization of a separate group of rabbits with 6-ketoprostaglandin F1 alpha-hyperimmune plasma, obtained from actively 6-ketoprostaglandin F1 alpha-immunized donor rabbits that had ulcers, induced gastric ulceration within 9 days, whereas passive immunization of rabbits with control plasma, obtained from donor rabbits actively immunized with thyroglobulin alone, did not induce ulceration. Ulcerogenic donor plasma containing antibody to 6-ketoprostaglandin F1 alpha neutralized the inhibitory actions of prostacyclin on adenosine diphosphate-induced platelet aggregation, indicating that this antibody cross-reacted with prostacyclin. In contrast, plasma containing antibodies to 13,14-dihydro-15-ketoprostaglandin E2 cross-reacted only slightly with prostaglandin E2. Thus antibodies to inactive metabolites of prostaglandins induce ulceration only if these antibodies cross-react with an endogenous, "cytoprotective" prostaglandin.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Antibody Formation; Dinoprostone; Gastric Mucosa; Immunization; Immunization, Passive; Intestinal Diseases; Intestinal Mucosa; Male; Rabbits; Stomach Ulcer; Thyroglobulin; Ulcer

This study investigated the relationship between the protective effect of sucralfate against ethanol-induced gastric mucosal injury in the rat and the effects of sucralfate on prostaglandin and mucus synthesis and secretion. Sucralfate at 200, 400, and 800 mg/kg significantly reduced gastric ulceration. Intragastric administration of sucralfate increased luminal mucus and prostaglandin E2 levels but did not affect prostaglandin or mucus synthesis in gastric mucosal biopsy specimens from sucralfate-treated animals. Pretreatment with indomethacin partially reduced the protective effect of sucralfate. However, sucralfate 200 mg/kg, a dose that completely prevented ulceration, did not increase the levels of luminal prostaglandin E2. In vitro incubation with sucralfate did not stimulate mucosal prostaglandin synthesis. Longer-term administration of sucralfate for 48 or 96 hours did not stimulate mucus or prostaglandin synthesis but did increase luminal prostaglandin E2 and mucus. Although sucralfate increased the gastric juice content of prostaglandin E2 and mucus, the two did not appear to be mechanistically related, and only mucus release was consistently associated with mucosal protection.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dinoprostone; Ethanol; Gastric Mucosa; Indomethacin; Male; Mucus; Prostaglandins E; Rats; Rats, Inbred Strains; Stomach Ulcer; Sucralfate

Clonidine and paraaminoclonidine prevented the formation of indomethacin-induced gastric ulcers in female rats. This protective activity was blocked by coadministration of yohimbine. Therefore, the antiulcer activity of clonidine was due to its peripheral alpha-2 agonistic action. Because indomethacin is a prostaglandin synthetase inhibitor, its ulcerogenic effect has been attributed to a state of prostaglandin (PG) deficiency. We therefore investigated the possibility that the protective effect of alpha-2 adrenoceptor agonists could be mediated by stimulation of the biosynthesis of PGs in the stomach. However, the results failed to show increased production of PGE2 or 6-keto-PGF1, either in stomach slices in vitro or in the gastric mucosa of rats pretreated with clonidine, whether indomethacin was used or not. It is concluded that the activity of clonidine in preventing indomethacin-induced gastric erosions in rats is probably not related to prostaglandins.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Clonidine; Dinoprostone; Female; Gastric Mucosa; Indomethacin; Prostaglandins E; Rats; Stomach Ulcer; Yohimbine

"Mild irritants" have been shown to protect rat gastric mucosa from damage induced by noxious topical agents, supposedly by induction of mucosal prostaglandin (PG) biosynthesis. The protective effect of NaCl 5%, ethanol 20%, NaOH 0.075 N, HCl 0.35 N, salicylic acid 100 mg/kg and paracetamol 200 mg/kg was investigated in rats treated with an ulcerogenic dose (25 mg/kg) of indomethacin; mucosal PG synthesis was simultaneously determined. Significant protection was achieved only with NaCl 5%, salicylic acid and paracetamol. Salicylic acid and paracetamol significantly decreased acid secretion and enhanced PGE2 or 6-keto PGF1 alpha generation in control rats, while a small but significant change in the indomethacin-inhibited PG synthesis was observed after treatment with NaCl 5% or salicylic acid. We conclude that protection by "mild irritants" against indomethacin-induced mucosal damage may involve increased cytoprotective PG generation, as shown for paracetamol and salicylic acid, or partial blocking of indomethacin binding at the cyclooxygenase receptor site, as shown for NaCl 5% and salicylic acid.

Topics: 6-Ketoprostaglandin F1 alpha; Acetaminophen; Animals; Dinoprostone; Ethanol; Gastric Acid; Gastric Mucosa; Indomethacin; Irritants; Male; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Prostaglandins E; Rats; Salicylates; Salicylic Acid; Saline Solution, Hypertonic; Sodium Hydroxide; Stomach Ulcer

Sucralfate promotes the healing of peptic ulcers and, in large doses, increases gastric mucosal prostaglandins. The present study was designed to further elucidate the protective effect of sucralfate and to evaluate the role of prostaglandins in this action. Eight chair-adapted rhesus monkeys received a subcutaneous injection of either 150 mg/kg of aspirin or vehicle in combination with either a therapeutic oral dose of sucralfate (50 mg/kg X day) or water. Gastric soluble mucus concentration was determined in samples of gastric juice by Alcian blue dye binding of acidic glycoproteins, and mucus output was determined using a technetium 99m-diethylenetriaminepentaacetic acid dilution technique. Monkeys underwent endoscopy to assess gastric mucosal damage, which was ranked blindly on a scale of 0-5, and to obtain biopsy specimens for determination of mucosal prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha. Aspirin did not alter soluble mucus but did significantly increase gastric mucosal damage and suppress tissue levels of all prostaglandins. Sucralfate significantly increased the output of soluble mucus, even after aspirin treatment, and protected against aspirin-induced damage, although it did not modify aspirin-induced suppression of prostaglandins. These results suggest that the gastric protection afforded by sucralfate is related to a prostaglandin-independent increase in mucus production.

Topics: 6-Ketoprostaglandin F1 alpha; Aluminum; Animals; Anti-Ulcer Agents; Aspirin; Dinoprost; Dinoprostone; Macaca mulatta; Mucus; Prostaglandins; Prostaglandins E; Prostaglandins F; Stomach Ulcer; Sucralfate

Effects of indomethacin on gastric motility and secretion, and levels of endogenous prostaglandins (PGs) were investigated in rats, in attempts to elucidate the factors involved in the pathogenesis of indomethacin-induced macroscopic gastric lesions. Subcutaneous administration of indomethacin had no effect on the gastric mucosa at doses of 1 and 5 mg/kg, but induced visible lesions dose dependently at over 10 mg/kg within 4 hr. At 25 mg/kg, there were apparent nonhemorrhagic lesions within 1 hr, and these lesions became hemorrhagic with time. Acid secretion was not affected by this agent at either dose level, but pepsin or acid-induced HCO3- secretion was significantly increased or decreased, respectively, at a dose less than 5 mg/kg, which did not induce any lesion. Gastric motility, however, was dose dependently increased after administration of indomethacin, and its effect was significant at 10 mg/kg or greater. Time-course changes in the motility were in parallel with those of the lesion formation. PGE2 and 6-keto PGF1 alpha levels in the corpus mucosa were reduced around 80-90% for more than 4 hr from 30 min after administration of 5 mg/kg or more of indomethacin. When all the above changes caused by indomethacin were plotted for the various doses, a significant correlation (r = 0.958, P less than 0.01) was found between the lesion index and the changes in motility, but not in other factors, including PG levels. These results indicate that gastric motility may be an important factor in the pathogenetic mechanism of indomethacin-induced gastric lesions in rats. A deficiency of endogenous PGs may be a prerequisite for later extension of the lesions.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dinoprostone; Gastric Mucosa; Gastrointestinal Motility; Indomethacin; Male; Prostaglandins E; Rats; Stomach Ulcer

The authors compare the effect of indomethacin and proglumetacin on the production of prostacyclin in the rat gastric mucosa, and investigate the potential ulcerogenic effect elicited by the two drugs. The results show that indomethacin and proglumetacin, at doses giving similar inhibition of gastric-protacyclin synthesis, drastically differ in their gastric ulcerogenic effects.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Epoprostenol; Gastric Mucosa; Indoleacetic Acids; Indomethacin; Male; Rats; Rats, Inbred Strains; Stomach Ulcer

The effects of 3-(1-methylethyl)-2-(4-methoxyphenyl)-3H-naphth [1,2-d]imidazole, MDL 035, a new non-steroidal non-acidic anti-inflammatory compound, on the production of prostaglandin (PG) in rat gastric mucosa in vivo and in vitro and in inflammatory exudate in vivo were studied. MDL 035 reduced PGE2 and 6-keto-PGF1 alpha levels more effectively in inflamed tissue than in gastric mucosa when assayed in in vivo experiments, whereas indomethacin and other non-steroidal anti-inflammatory drugs (NSAIDS) are equally effective in both systems. MDL 035 is almost as active as indomethacin when incubated with gastric tissue in vitro. The better gastric tolerance of MDL 035 than of other NSAIDS is discussed in relation to these differences in in vivo and in vitro effects.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Dinoprostone; Dose-Response Relationship, Drug; Exudates and Transudates; Gastric Mucosa; Imidazoles; In Vitro Techniques; Indomethacin; Inflammation; Male; Naproxen; Prostaglandins; Prostaglandins E; Rats; Stomach Ulcer

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Cold Temperature; Gastric Mucosa; Humans; Indomethacin; Male; Prostaglandins; Prostaglandins E; Rats; Rats, Inbred Strains; Restraint, Physical; Stomach Ulcer; Stress, Psychological; Thromboxane B2

Several prostaglandins were found to protect the gastric mucosa against the ulcerogenic effect of immobilization (stress) and of indomethacin in the rat. The analogue 6-keto-prostaglandin-F1 alpha had no cytoprotective effect in the same region and even seemed to facilitate ulceration in the stomach in a dose-dependent manner. Unusually high doses of this prostaglandin analogue also exerted a slight cytoprotective effect.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dose-Response Relationship, Drug; Epoprostenol; Female; Gastric Mucosa; Humans; Indomethacin; Rats; Rats, Inbred Strains; Restraint, Physical; Stomach Ulcer; Stress, Psychological