Effect of peroxisome proliferator-activated receptor-alpha agonist (bezafibrate) on gastric secretion and gastric cytoprotection in rats

The effect of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) on gastric secretion and gastric cytoprotection was evaluated using five different models of gastric ulcers: acetic acid-induced chronic gastric ulcers, pylorus ligation, ethanol-induced, indomethacin-induced and ischemia-reperfusion-induced gastric ulcers. Bezafibrate, a PPAR-alpha agonist was administered at two different doses of 10 and 100 mg/kg body weight intraperitoneanally. Both doses of bezafibrate showed significant antiulcer effect in ethanol-induced, indomethacin-induced and pylorus ligation-induced gastric ulcers. Bezafibrate increased healing of ulcer in acetic acid-induced chronic gastric ulcer model. Both doses were also effective in preventing gastric lesions induced by ischemia-reperfusion. It was concluded that PPAR-alpha activation increases healing of gastric ulcers and also prevents development of gastric ulcers in rats.     

Antisecretory and antiulcer activities of a novel proton pump inhibitor AG-1749 in dogs and rats

The antisecretory and antiulcer activities of 2[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl] sulfinyl]-1H-benzimidazole (AG-1749) were investigated in dogs and rats. AG-1749 inhibited both the (H+ + K+)-adenosine triphosphatase activity in canine gastric microsomes and dibutyryl cyclic AMP-stimulated acid formation in isolated canine parietal cells and suppressed the acid secretion stimulated by histamine, pentagastrin, bethanechol or a peptone meal in Heidenhain pouch dogs; the ID50 values were between 0.2 and 0.7 mg/kg p.o. AG-1749 inhibited both the histamine-stimulated and the basal acid secretion in pylorusligated rats and prevented water immersion stress or aspirin-induced gastric lesions and mepirizole or cysteamine-induced duodenal ulcers in rats; the ID50 values were between 0.3 to 3.6 mg/kg p.o. or i.d. Furthermore, AG-1749 prevented gastric lesions induced by absolute ethanol or acidified aspirin, and accelerated the healing of acetic acid-induced gastric or duodenal ulcers in rats. The inhibitory potency of AG-1749 in dogs was much the same as that of omeprazole and about half that of ranitidine. However, it was about 2 to 10 times more potent than omeprazole and 4 to 34 times more potent than ranitidine in rats. These results suggest that AG-1749 exerts prominent antiulcer activities mainly by suppressing acid secretion via an inhibition of a proton pump in gastric parietal cells and partly by protecting the gastrointestinal mucosa against various ulcerative stimuli.     

Regulation by endogenous interleukin-1 of mRNA expression of healing-related factors in gastric ulcers in rats.

We investigated the role of endogenous interleukin (IL)-1 in the mRNA expression of cyclooxygenase (COX)-1, COX-2, inducible nitric oxide synthase (iNOS), cytokine-induced neutrophil chemoattractant (CINC)-1, epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and transforming growth factor (TGF)-beta1 in acetic acid-induced gastric ulcers in rats. IL-1beta mRNA was not detected in the normal or intact mucosa of ulcerated stomachs, but its expression was induced in the ulcerated tissue. IL-1beta immunoreactivity was observed in macrophages/monocytes and fibroblasts in the ulcer base. COX-2, iNOS, and CINC-1 mRNAs were expressed by ulceration. EGF, bFGF, HGF, and TGF-beta1 mRNA expression was detected in the normal mucosa, and their levels were significantly elevated by ulceration. In contrast, COX-1 mRNA level did not differ between the normal and ulcerated tissues. In a culture of isolated ulcer bases, block of IL-1 with IL-1 receptor antagonist (IL-1RA) dose-dependently and significantly reduced the mRNA levels of COX-2, iNOS, CINC-1, HGF, and bFGF. In contrast, COX-1, EGF, and TGF-beta1 mRNA expression was not affected by IL-1RA. IL-1RA dose-dependently reduced prostaglandin E(2) production, total and iNOS activities, neutrophil chemotactic activity, and growth-promoting activity toward gastric epithelial cells in the ulcer base. Finally, the administration of IL-1RA caused a significant impairment of ulcer healing. These results indicate that IL-1, expressed in macrophages/monocytes and fibroblasts in the ulcer base, might up-regulate the mRNA expression of COX-2, iNOS, CINC-1, HGF, and bFGF, thereby contributing to gastric ulcer healing in rats.     

Sucralfate compared with ranitidine in the short-term healing of duodenal ulcers

The efficacy of sucralfate (1 g four times daily) and ranitidine (150 mg twice daily) in the short-term healing of duodenal ulcers has been assessed in a randomized single-blind trial involving 104 patients with three drop-outs. The healing rate at 3 weeks of 83% for sucralfate and 84% for ranitidine improved to 96% and 92%, respectively, at 6 weeks. The difference between the two treatment groups was not statistically significant. Smoking and male sex had no influence on the healing rates. Constipation was a prominent symptom in sucralfate treatment which was otherwise a safe and effective therapy.     

Ulceration after esophageal and gastric variceal sclerotherapy--influence of sucralfate and other factors on healing

Forty-five consecutive patients underwent sclerotherapy with absolute alcohol. Post-sclerotherapy ulcers were detected in all of them (100%) on the following day. In order to evaluate its influence on ulcer healing, 20 patients were given sucralfate (1 g QID before meals), while 25 patients received identical-looking placebo, in a double-blind randomised manner. Endoscopy done at weekly intervals revealed healing of ulcers in 25%, 55%, 95% and 100% in the sucralfate, and 24%, 40%, 72% and 84% in the placebo group at 1, 2, 3, and 4 weeks, respectively. Differences between the two groups were not significant. Gastric variceal ulcers healed better with sucralfate (7 out of 7) than placebo (0 out of 2). Healing was influenced by the size of the ulcer. At two weeks, 63% of ulcers less than 1 cm, 43% of ulcers 1-2 cm, and only 16.6% of ulcers greater than 2 cm had healed. The size of the ulcer also correlated with the amount of the sclerosant injected. Our results show that (a) mucosal ulcers universally develop after adequate sclerotherapy, (b) most ulcers heal spontaneously, (c) sucralfate does not hasten ulcer healing, with the exception of gastric variceal ulcers, (d) a larger amount of sclerosant produces larger ulcers that take longer to heal.     

Relapse of peptic ulcer after quick healing induced by proton pump inhibitors]

Peptic ulcers treated with a proton pump inhibitor heal more quickly than those treated with a histamine H2 receptor antagonist. Although satisfactory healing without relapse is desirable in the medical treatment of peptic ulcers, the relapse rate after treatment with proton pump inhibitors has not been sufficiently studied. Up to now, several reports have suggested that peptic ulcers treated with omeprazole recur less frequently than those treated with H2 antagonists. Our experimental studies on angiogenesis in granulation tissue of acetic acid-induced gastric ulcers, gastric mucosal collagen synthesis etc., show that H2 antagonists have an inhibitory effect on wound healing, but that proton pump inhibitors do not. It is suggested, therefore, that proton pump inhibitors may at least have no undesirable effect on the natural history of peptic ulcer.     

Campylobacter pylori, gastritis and peptic ulcer

In the course of routine gastroduodenoscopic examination of 218 patients bioptic mucosal specimens were examined bacteriologically for the presence of Campylobacter (C.) pylori. The organism was isolated from 52 out of 53 patients (98%) with duodenal ulcer, 7 out of 9 with gastric ulcer (78%), 24 out of 31 with mucosal erosions (77%), 10 out of 10 with duodenitis (100%), 16 out of 16 with chronic active gastritis (100%) and from 40 out of 73 patients (55%) with inactive chronic gastritis. By contrast, all specimens from 26 patients with endoscopically and histologically normal mucosa were negative for this bacterium. The rate of elimination of C. pylori from mucosal specimens was investigated as a first step towards studying the influence of antibiotic therapy upon healing of gastric and duodenal ulcers. For this purpose 30 patients with duodenal ulcers were treated either with ranitidine alone (15) or together with bacampicillin (15), which was shown to be highly active in studies with ampicillin in vitro. After 4 weeks the organism was still found in specimens from all patients treated with ranitidine alone, but also in 12 out of 15 patients given combined therapy. This result demonstrates that systemic antimicrobial chemotherapy with bacampicillin is insufficient to eradicate C. pylori from the stomach and the duodenum.     

Effect of (S)-4-(1-(5-chloro-2-(4-fluorophenyoxy)benzamido)ethyl) benzoic acid (CJ-42794), a selective antagonist of prostaglandin E receptor subtype 4, on ulcerogenic and healing responses in rat gastrointestinal mucosa

Recent research showed the involvement of prostaglandin E receptor subtype 4 (EP4) in hypersensitivity to inflammatory pain and suggested that the EP4 receptor is a potential target for the pharmacological treatment of inflammatory pain. We examined the effects of (S)-4-(1-(5-chloro-2-(4-fluorophenyoxy) benzamido)ethyl) benzoic acid (CJ-42794), a selective EP4 antagonist, on gastrointestinal ulcerogenic and healing responses in rats, in comparison with those of various cyclooxygenase (COX) inhibitors. CJ-42794 alone, given p.o., did not produce any damage in the gastrointestinal mucosa, similar to 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560) (COX-1 inhibitor) or rofecoxib (COX-2 inhibitor), whereas indomethacin (nonselective COX inhibitor) caused gross lesions. Rofecoxib but not CJ-42794, however, damaged these tissues when coadministered with SC-560 and aggravated gastric lesions produced by aspirin. Indomethacin and SC-560 worsened the gastric ulcerogenic response to cold-restraint stress, yet neither CJ-42794 nor rofecoxib had any effect. Furthermore, indomethacin and SC-560 at lower doses damaged the stomach and small intestine of adjuvant arthritic rats. In arthritic rats, rofecoxib but not CJ-42794 provoked gastric ulceration, whereas CJ-42794 produced little damage in the small intestine. The repeated administration of CJ-42794 and rofecoxib as well as indomethacin impaired the healing of chronic gastric ulcers with a down-regulation of vascular endothelial growth factor expression in the ulcerated mucosa. These results suggest that CJ-42794 does not cause any damage in the normal rat gastrointestinal mucosa and in the arthritic rat stomach and does not worsen the gastric ulcerogenic response to stress or aspirin in normal rats, although this agent slightly damages the small intestine of arthritic rats and impairs the healing of gastric ulcers.     

Ranitidine in the treatment of gastric, prepyloric and duodenal ulcer--a controlled prospective double-blind trial

Fifty adult outpatients with endoscopically proven gastric, prepyloric or duodenal ulcers were included in a prospective, randomised double-blind trial of ranitidine (40 mg X 3 daily and 80 mg at bedtime) versus placebo. After 4 weeks the ulcers had healed in 21 of 25 patients receiving ranitidine compared with 7 of 23 in patients receiving placebo (p less than 0.001). The ranitidine treated patients had fewer days of pain (p less than 0.001) and lower consumption of antacids (p less than 0.01) than placebo patients. Patients whose ulcers were not healed after 4 weeks went into an open 4 weeks trial with ranitidine. After the second 4 week period there were still 5 unhealed ulcers, all located in the prepyloric region. No serious side effects or haematological or biochemical abnormalities were observed. It is concluded that ranitidine is a very potent and safe ulcer healing substance. Patients with prepyloric ulcers may need a higher dose or a longer period of treatment.     

黄芪对大鼠应激性胃溃疡的预防作用

目的观察黄芪注射液对应激状态下大鼠胃黏膜损伤有无保护作用。方法采用水浸束缚应激方法复制大鼠应激性溃疡模型。将40只健康大鼠随机分为5组：对照组、模型组、黄芪10g／kg、20g／kg组和硫糖铝500mg／kg给药组。分别连续灌胃给予黄芪或硫糖铝5d后复制模型，6h后取胃计算溃疡指数，采用光镜观察大鼠胃组织病理改变。结果水浸束缚应激致应激性溃疡形成，胃黏膜出现广泛的糜烂、出血。黄芪和硫糖铝均可显著降低溃疡指数（P〈0．01），其中黄芪20g／kg疗效最佳，优于硫糖铝500mg／kg（P〈0．05）。黄芪可显著减轻大鼠胃黏膜细胞损伤程度和毛细血管及其周围间质的水肿。结论黄芪对应激性溃疡大鼠具有显著的胃黏膜保护作用。     

Gastric and duodenal antiulcer and cytoprotective effects of proglumide in rats

Proglumide has been studied for its ability to inhibit gastric secretion and to protect the gastroduodenal mucosa against the injuries caused by pyloric ligation, hypothermic restraint stress, acetic acid, nonsteroid anti-inflammatory drugs, reserpine, cysteamine and the cytodestructing agents: 80% ethanol, 0.6 M HCl, 0.2 M NaOH, 25% NaCl and 30 mg of acetylsalicylic acid in 0.35 M HCl in rats. The results of this study demonstrate that proglumide has both prophylactic and curative effects on various experimentally induced ulcers. It produced a dose-dependent inhibition of gastric secretion in the pylorus-ligated rats and reduced significantly the intensity of gastric lesions induced by pyloric ligation, hypothermic restraint stress, acetic acid, mucosal damaging agents and that of duodenal ulcers induced by cysteamine. The intensity of gastric lesions induced by nonsteroid anti-inflammatory drugs and reserpine was also reduced significantly by proglumide. Cimetidine, which was used as a standard antiulcer drug for comparison, also produced a similar protective effect in most of the models used by us. It was found to have a more potent antisecretory effect but failed to protect the rats against the gastric mucosal damage induced by hyperthermic restraint stress and 0.2 M NaOH. Our findings suggest that proglumide exerts these antiulcer effects by its antisecretory, gastric mucosal resistance increasing and cytoprotective activities. Further studies are required to find out its exact mechanism of action and therapeutic usefulness.     

Histopathologic characteristics of gastric ulcers created by endoscopic submucosal dissection

BACKGROUND AND STUDY AIM: We have previously reported that gastric ulcers artificially created by endoscopic submucosal dissection (ESD) would heal within 8 weeks regardless of size and location. The details of the healing process remain unclear, and we aimed to clarify the mechanism by histopathological investigation. PATIENTS AND METHODS: 21 post-ESD ulcers were examined histopathologically, using surgically resected specimens from patients who had subsequently undergone gastrectomy due to submucosal invasion and/or lymphovascular infiltration by the tumor. The grade of ulcer, appearance of regenerative mucosa, scar formation, and extent of fibrosis were evaluated. RESULTS: Fibrosis and wall thickening were observed from 2 weeks after ESD, but regenerative mucosa was not observed until 5 weeks. Among 12 patients who underwent gastrectomy later than 8 weeks after ESD, a mucosal defect was still observed in two patients. In these two patients the lesion was associated with severe fibrosis due to previous peptic ulcer or submucosal invasion by the lesion. CONCLUSION: Size reduction in these ulcers occurs by contraction in the early phase, then regenerative mucosa covers the remaining mucosal defect within 8 weeks. If there is fibrosis under the lesion before ESD, there is a possibility that the artificially created ulcer will not heal within 8 weeks.     

Complementarity of in vitro and in vivo models for the evaluation of gastro‐protective effects of pharmacological substances

Gastric mucosa is frequently exposed to various gastric irritants, and there is a continuing requirement to develop new gastro‐protective agents. This study compares the effects of three such agents, sucralfate, rebamipide, and cimetidine in both in vivo and in vitro indomethacin‐induced gastric damage models. For the in vivo approach, rats were orally administered sucralfate, rebamipide, and cimetidine at 300 mg/kg before an acute dose of indomethacin (30 mg/kg). Gastric lesions were then macroscopically examined. For the in vitro approach, gastric mucosal cells were incubated with sucralfate (3 and 5 mg/mL), rebamipide (0.3 and 1 mm ), and cimetidine (10 and 50 μg/mL) before exposure to indomethacin (3.8 mm ). The release of lactate dehydrogenase (LDH) and mitochondrial function were then measured. Sucralfate, rebamipide, and cimetidine displayed gastro‐protective effects in vivo (decreased number of gastric ulcers: ?50% P < 0.05, ?22% NS, and ?69% P < 0.05, respectively, and reduced length of gastric lesions: ?62% P < 0.05, ?29% NS, and ?70% P < 0.001, respectively). Cell damage induced by indomethacin in vitro was inhibited by sucralfate (LDH release) and by rebamipide and cimetidine (mitochondrial function and LDH release). In contrast, sucralfate accentuated the indomethacin‐induced decrease in mitochondrial function. Although cultured gastric cells offer a promising tool for evaluating the cytotoxic or protective effects of test compounds, data from in vivo models are still needed to confirm in vitro data. Using both approaches provides more comprehensive insight into the effects of test compounds on the gastric mucosa.     

Glutathione, protein sulfhydryls and cysteine proteases in gastric mucosal injury and protection.

Glutathione is one of the endogenous protective chemicals, like prostaglandins, in the gastric mucosa. Depletion of these agents aggravate the chemical- or stress-induced gastric erosions and ulcers. However, gastroprotection can be achieved even in the presence of low mucosal concentration of glutathione and prostaglandins, indicating the presence of other protective chemicals (e.g. polyamines, growth factors, neurotransmitters, steroids) in the stomach. Protein sulfhydryls were also implicated in the mechanism of action of gastroprotective drugs. We recently tested the hypothesis that cysteine proteases might be a target of gastroprotective and antiulcer agents, and decided to look for the presence of proteases and protease inhibitors (PI) in the gastric mucosa and juice. Protease activity and PI were measured with general substrates hemoglobin, azocasein and albumin at optimal pH (2.0, 5.6, 7.4) of aspartic, cysteine and serine proteases. Homogenates of glandular stomach mucosa and gastric juice from fasted rats were incubated in the presence or absence of specific inhibitors and gastroprotective SH alkylators such as NEM or iodoacetate. PI was measured after acid and heat inactivation of endogenous proteinases and addition of pepsin, cysteine proteinase papain, or trypsin. Our results indicate that of the proteases found in the stomach 98% was pepsin at pH 2.0, and up to 56% or 24% was SH-sensitive at pH 5.6 or 7.4, respectively. Intragastric administration of SH alkylators such as NEM or iodoacetate exerted a dose- and time-dependent gastroprotection against chemically induced acute erosions and ulcers. Thus, in addition to glutathione, proteinases and their specific endogenous inhibitors may also be involved in gastric mucosal injury and protection.     

Evaluation of chromo-endoscopy for diagnosis of histological repair of gastric ulcer]

The chromoendoscopic features of healed gastric ulcers were investigated by the methylene blue test. Histological repair of healed ulcers was graded as either Ul3 (incompletely healed) or Ul4 (completely healed). Endoscopically, the Ul4 scar was observed as a flat granular area without any depression, and sometimes associated with redness, the Ul3 scar was observed as a distinct depression in the surrounding normal mucosal surface, and usually associated with homogenous redness. Follow-up studies of patients with Ul4 and Ul3 lesions showed that recurrence was significantly rare in patients with the Ul4 lesion than in patients with the Ul3 lesions. These findings indicate that healing of gastric ulcers should be defined endoscopically as crater disappearance. At 8 weeks after treatment with omepral, most of the ulcers were healed, but judged a as Ul3 scar.     

Is there still a role for sucralfate in the treatment of gastritis?

The endoscopic diagnosis of gastritis is usually made when a patient develops symptoms and undergoes an upper gastrointestinal endoscopy. There are often obvious aetiological causes such as smoking, alcohol Helicobacter pylori infection or drug treatment. Lifestyle changes can sometimes improve symptoms but often patients will be treated with a proton pump inhibitor. The stomach mucosa produces a protective mucous to prevent damage cause by gastric acid and exogenous agents can disrupt this layer. Repair of this protective layer can be enhanced by reduction in gastric acid secretion using H2 receptor antagonist or proton pump inhibitors or by cytoprotective drugs such as misoprostol, sucralfate, aluminium ions or bismuth subsalts. Sucralfate is a complex polymer which at a low pH changes its chemical configuration and binds to serum protein to form a protective layer protecting the mucosa against further injury. Cytoprotective drugs were the first line treatment for peptic disease including gastritis for many years but since the launch of cimetidine in 1976 and the subsequent launch of omeprazole in 1988, their use has slowly declined. First line treatment for patients with symptomatic gastritis after removal of potential causative factors is likely to be a proton pump inhibitor in 2019. This is despite the fact that there is some evidence that sucralfate is superior than a H2 receptor antagonist in the endoscopic healing rates in patients with gastritis. The logical treatment choice in patients with resistance symptoms is a combination of a proton pump inhibitor and sucralfate but evidence is lacking. Until such evidence is available In the meantime, we would suggest that there is a role for sucralfate in the treatment of intransigent gastritis and that mucosal protection should be considered even ahead of acid suppression given its favourable safety and toxicity profile.     

Effects of ranitidine and sucralfate on ketoconazole bioavailability.

Ketoconazole is an oral imidazole antifungal agent useful in the treatment of opportunistic fungal infections. Gastrointestinal absorption of this agent is variable and dependent on the presence of gastric acid. This study compared the effects of concomitant sucralfate administration with ranitidine administration on the pharmacokinetic disposition of a 400-mg ketoconazole dose. Six healthy male volunteers were randomized to receive 400 mg of ketoconazole alone, 1.0 g of sucralfate concomitantly with a 400-mg ketoconazole dose, or ranitidine, administered 2 h prior to a 400-mg ketoconazole dose to titrate to a gastric pH of 6. All subjects received all three regimens in crossover fashion. Gastric pH was measured continuously for 4 h after ketoconazole administration in all subjects by using a Heidelberg radiotelemetry pH capsule. Relative ketoconazole bioavailability was compared between treatments. With sucralfate, five of six subjects demonstrated a decrease in the peak drug concentration in serum as well as an increase in the time to peak concentration, indicating a delay in ketoconazole absorption. The mean area under the concentration-time curve from 0 to 12 h for ketoconazole following gastric alkalinization was significantly different from that of either ketoconazole alone or ketoconazole with sucralfate (P less than 0.01). Continuous gastric pH monitoring allowed correlation between the decrease in ketoconazole bioavailability observed with ranitidine and the increase in gastric pH. The apparent decrease in ketoconazole bioavailability observed with sucralfate appears to be caused by an alternative mechanism since a change in gastric pH was not observed. On the basis of these findings, separating the administration of ketoconazole and sucralfate should be considered to decrease the potential for interaction of sucralfate on ketoconazole bioavailability.     

Gastric ulcer healing after treatment of endoscopic submucosal dissection in Japanese: comparison of H(2) receptor antagonist and proton pump inhibitor administration

Endoscopic submucosal dissection has made it possible to resect large lesions during a single operation. The present study was undertaken to compare the time taken for recovery from artificial ulcers after endoscopic submucosal dissection between an H(2) Receptor Antagonist treatment group and a Proton Pump Inhibitor treatment group, focusing on analysis of the time course of reduction rate in ulcer area. The powerful acid suppression by Proton Pump Inhibitor may not be needed to treat Japanese post-endoscopic submucosal dissection ulcer which usually develops after early gastric carcinoma in the mucosa of low acid secretory capacity. The study involved 60 patients with 69 artificial ulcers following endoscopic submucosal dissection for the treatment of tumors remaining in the gastric mucosa. Of all lesions, 36 were allocated to the H(2) Receptor Antagonist group and 33 to the Proton Pump Inhibitor group. Patients in both groups underwent endoscopy at 4 and 8 weeks after the start of administration. There were no significant differences between two groups and ulcer healing rates were similar in the two groups. The efficacy of H(2) Receptor Antagonists in curing this type of ulcer can thus be expected to be comparable to that of Proton Pump Inhibitors.     

Studies on changes in lipid profiles of the rat gastric mucosa with stress ulcers.

Gastric mucosal lipid patterns were studied in normal and in restrained rats which developed mucosal erosions. Organic solvent extraction, silicic acid column, and thin-layer chromatography were employed to separate and gas-liquid chromatography and spectrophotometry to quantitize the individual lipid components. Chemical analysis revealed profound alterations in the mucosal lipid profiles of rats with gastric mucosal erosions. Cholesterol esters were markedly elevated, cholesterol, free fatty acids and phosphatidylethanolamine were markedly lower in the extracts of ulcerated tissue, and the titer of lysophospholipids was about eight times higher than in the controls. Lipid phosphorus was elevated in stressed rats. The amount of neutral glycolipids was similar for both groups, but tetra- and oligohexoside ceramides, which were present in the gastric mucosa of the control rats, were virtually absent from the ulcerated mucosa. In contrast to the alterations in lipid profile mentioned above, the total lipid weight per tissue preparation was very similar for the ulcerated and normal control groups.     

Gastric antiulcer and cytoprotective effects of dipyridamole in rats

Dipyridamole has been studied for its ability to inhibit gastric secretion and to protect gastric mucosa against the injuries caused by hypothermic restraint stress, indomethacin and various necrotizing agents including 80% ethanol, 0.6 M HCl, 0.2 M NaOH and 25% NaCl in rats. The results of this study demonstrate that dipyridamole has both prophylactic and curative effects on various experimentally induced gastric ulcers. It produced inhibition of normal and histamine-stimulated gastric secretion in rats. The intensity of gastric lesions induced by indomethacin and hypothermic restraint stress was reduced significantly by dipyridamole. Our findings also showed that dipyridamole protect gastric wall against hypothermic restraint stress-induced mucus depletion. It produced marked cytoprotective effect against all the necrotizing agents used in this study. The cytoprotective effect of dipyridamole against 80% ethanol was reversed significantly by prior treatment with a dose of indomethacin that inhibits prostaglandin biosynthesis. These data indicate that dipyridamole inhibits the formation of gastric lesions by mucosal generation of prostaglandins. The concentration of nonprotein sulfhydryls were decreased significantly in gastric mucosa after administration of 80% ethanol. Treatment with dipyridamole replenish the reduced level of gastric mucosal nonprotein sulfhydryls, thus suggesting the mediation of its protective effect through sulfhydryls. Our findings show that dipyridamole possesses both antisecretory and antiulcer effects. Further studies are required to determine its role in the prophylaxis and or the treatment of gastric ulcer disease.