Duodenal Ulcers In Rats Research Articles

Anti-ulcer activity of calcitonin gene-related peptide in rats

1. 1. Calcitonin gene-related peptide (CGRP, 5–10 μg/kg s.c.). reduced both incidence and degree of indomethacin- or acetylsalicylic acid (ASA) plus HCI-induced gastric as well as cysteamine-induced duodenal ulcers in rats. CGRP had no effect on ethanol-induced gastric lesions. 2. 2. The anti-ulcer activity of CGRP is most likely ascribable to its potent antisecretory properties.

Induction of duodenal ulcers in rats under water-immersion stress conditions: Influence of stress on gastric acid and duodenal alkaline secretion

We investigated the influence of stress on gastric acid and duodenal HCO3− secretion in rats, and examined whether duodenal ulcers develop in rats under stress conditions in the absence or presence of acid hypersecretion caused by histamine. Either restraint alone or restraint plus water-immersion stress induced lesions in the stomach but not in the duodenum. However, subcutaneous administration of histamine dihydrochloride (40 mg/kg every 2.5 h for a total of three times) to stressed rats produced macroscopically visible damage in the proximal duodenum as well as in the stomach within 8 h of exposure to stress, and the incidence of duodenal lesions was 100% in the water-immersion group (24.8 ± 3.8 mm2, n = 8). Histamine alone had no effect on either region. These lesions in the duodenum caused by water immersion plus histamine were prevented by subcutaneously administered cimetidine (30, 100 mg/kg) or 16,16-dimethyl prostaglandin E2 (10, 30 μg/kg) in a dose-related manner, but not by atropine (1, 3 mg/kg). Restraint decreased acid secretion by 40%, and additional water immersion restored the decreased acid secretion to normal levels. Basal duodenal HCO3− secretion was decreased to about 70% of normal values (5–6 μEq/15 min) in the restraint group, and after additional water immersion further declined to the values of 1.5–2 μEq/15 min. An increase of HCO3− secretion caused by acid was significantly inhibited by water immersion but not by restraint. Histamine significantly increased acid secretion but did not affect duodenal HCO3− secretion. In the rats treated with both water immersion and histamine, acid secretion was significantly reduced by either cimetidine (100 mg/kg) or 16,16-dimethyl prostaglandin E2 (30 μg/kg), whereas duodenal HCO3− secretion was significantly increased by 16,16-dimethyl prostaglandin E2. Atropine had little effect on either acid or HCO3− secretion. These results suggest that exposure of rats to stress decreases duodenal HCO3− secretion and increases the susceptibility of the mucosa to acid emptied from the stomach, thereby inducing duodenal ulcers if acid hypersecretion is concomitantly present.

Oral administration of synthetic human urogastrone promotes healing of chronic duodenal ulcers in rats

The effect of oral administration of synthetic human epidermal growth factor/urogastrone (EGF/URO) on healing of chronic duodenal ulcers induced by cysteamine in rats was investigated and compared with that of cimetidine, a H2-receptor antagonist. After 25 and 50 days of treatment, synthetic human EGF/URO significantly increased healing of chronic duodenal ulcers to the same extent as cimetidine. Combined treatment with synthetic human EGF/ URO and cimetidine for 25 days was more effective than synthetic human EGF/URO given alone, whereas combined treatment for 50 days was significantly more effective than cimetidine alone. These results show that a combination of an agent inhibiting gastric acid secretion and the cytoprotective and growth-stimulating peptide EGF/URO seems to be more effective with regard to duodenal ulcer healing than individual administration of the two substances. Synthetic human EGF/URO is a potent inhibitor of gastric acid secretion when administered intravenously, but had no effect on acid secretion when given intraduodenally, which suggests that the effect of synthetic human EGF/URO is a direct action on the duodenal mucosa. In conclusion, this study showed that oral synthetic human EGF/URO has a significant effect on healing of duodenal ulcers in rats. The amount of synthetic human EGF/URO administered is comparable to that found in saliva during stimulation of the salivary glands. Our results, therefore, suggest that EGF/URO is one of the endogenous factors participating in healing of duodenal ulcers.

Evaluation of mastic, a crude drug obtained from Pistacia lentiscus for gastric and duodenal anti-ulcer activity

The effect of mastic, a concrete resinous exudate obtained from the stem of the tree Pistacia lentiscus, has been studied on experimentallyinduced gastric and duodenal ulcers in rats. Mastic at an oral dose of 500 mg/kg produced a significant reduction in the intensity of gastric mucosal damage induced by pyloric ligation, aspirin, phenylbutazone, reserpine and restraint + cold stress. It produced a significant decrease of free acidity in 6-h pylorus-ligated rats and a marked cytoprotective effect against 50% ethanol in rats which could be reversed by prior treatment with indomethacin. The protective effect was not seen when it was given intraperitoneally in phenylbutazone and restraint + cold stress models. The reduction in the intensity of ulceration in cysteamine-induced duodenal ulcers was not found to be statistically significant in mastic-pretreated rats. The results suggest that mild antisecretory and a localized adaptive cytoprotectant action may be responsible for its anti-ulcer activity. These observations support the results of an earlier study on the clinical effectiveness of mastic in the therapy of duodenal ulcer.

A New Model of Duodenal Ulcers Induced in Rats by Indomethacln Plus Histamine

We standardized a new method for producing duodenal ulcers in rats by administering indomethacin plus histamine, and investigated the pathogenesis. Indomethacin (5 mg/kg) was first given subcutaneously to rats fasted for 24 h, and subsequently histamine dihydrochloride (40 mg/kg) was given subcutaneously three times, at 2.5-h intervals, beginning 30 min after injection of indomethacin. This combined treatment induced one or two round lesions (9.8 +/- 1.4 mm2) in the proximal duodenum at an incidence of 100%, and a few lesions in the corpus and antrum of the stomach as well. Indomethacin or histamine alone had no effect on either the duodenum or the stomach. The lesions in the duodenum and antrum were inhibited by oral cimetidine (3-100 mg/kg) and 16,16-dimethyl prostaglandin E2 (dmPGE2) (3-30 micrograms/kg) in a dose-related manner, whereas those in the corpus were inhibited only by cimetidine. Indomethacin alone had no effect on gastric acid secretion, but did potentiate the increase of acid secretion caused by histamine. Histamine did not affect duodenal HCO3-secretion, whereas indomethacin slightly inhibited the basal HCO3-secretion and completely blocked the acid-stimulated HCO3-secretion. Intraduodenally administered cimetidine (30 mg/kg) or dmPGE2 (30 micrograms/kg) significantly inhibited acid secretion or increased HCO3-secretion, respectively, and both reduced the amount of acid emptied into the duodenum after treatment with indomethacin plus histamine. These results indicate that the development of duodenal lesions induced by indomethacin plus histamine in rats is due to both an increase in gastric acid secretion and an impairment of acid-induced duodenal HCO3-secretion. This newly established model will be useful for studying the pathogenesis of duodenal ulcers and for screening antiulcer agents.

Omeprazole Accelerates Healing of Cysteamine Induced Duodenal Ulcers in Rat

Cysteamine is a potent duodenal ulcerogen in rats (1). The pathogenesis of such ulcers comprises gastric acid hypersecretion (2,3), hypergastrinaemia (4), delayed gastric emptying (5,6), and inhibition of bicarbonate, mucus and EGF secretion by the duodenal Brunner's gland (7,8).

P-177 - Effects of DQ-2511, a new anti-ulcer agent, on experimental gastric and duodenal ulcers in rats

P-177 - Effects of DQ-2511, a new anti-ulcer agent, on experimental gastric and duodenal ulcers in rats

Effect of Cell Proliferation on Healing of Gastric and Duodenal Ulcers in Rats

The healing of acetic acid-induced gastric and duodenal ulcers was examined together with the biochemical indices of growth in gastric and duodenal mucosa in the following three groups of rats: (a) chow-fed, (b) fed an isocaloric liquid diet, (c) fed the liquid diet plus pentagastrin injections (250 micrograms/kg, 3 times/day). Animals received the diet regimen for 10 days from 1 day after induction of ulcer (day 0). Following the feeding regimens, serum gastrin levels, oxyntic gland mucosal DNA synthesis, and gastric secretory function were significantly lowered in the rats fed liquid diets. DNA synthesis in the duodenal mucosa was not different from the pre-ulcer levels. Pentagastrin significantly restored the DNA synthetic and gastric secretory activity of the liquid diet-fed rats toward the levels in the chow-fed group. In the latter group, a significant increase in DNA synthesis and levels of serum gastrin was found at day 6 (after 5 days feeding), which corresponded with a rapid, spontaneous healing of ulcers. Feeding rats liquid diet significantly delayed the healing of gastric, but not duodenal ulcers. Repeated administration of pentagastrin accelerated gastric ulcer healing in the liquid diet group toward the rate observed in the chow-fed group, but had no effect on the healing of duodenal ulcers. These results indicate that cell proliferation is an important factor in the healing of gastric ulcers.

Acute ethanol administration: Effects on stress-induced gastric and duodenal ulcer in rats

Rats were given 6% ethanol (v/v) as their only source of liquid for 4 days. On the basis of ethanol consumption (g/kg/day), animals were divided into high, medium and low ethanol consuming groups. A non-ethanol exposed control group was also included. Following a 24 hr food deprivation period, animals were restrained for 3 hr. No differences in gastric ulcer frequency or severity were noted with the exception of a slight tendency toward a lower incidence among ethanol consuming rats relative to controls. An unusual observation was the high incidence of duodenal ulcer observed only among ethanol consuming rats. This ethanol-stress interaction is discussed in terms of an animal's history of ethanol exposure.

Gastrointestinal morbidity among World War II prisoners of war: 40 years on.

A study of Australian male World War II veterans was conducted to assess clinically the gastrointestinal ill-effects which were present 40 years after the stress of internment as prisoners of war of the Japanese. A random sample of 170 surviving members of the captured Eighth Army Division resident in Sydney in 1983 (ex-POW) was compared with a similar sample of veterans who fought in Southeast Asia during the War, but were not imprisoned (non-POW). Duodenal ulcers and strongyloidiasis were more prevalent in the ex-POW group than in the non-POW group. The increased rate of duodenal ulcer (24.7%, compared with 10.5%; P = 0.0005) was confirmed by a higher proportion of ex-POWs currently taking cimetidine (9.0%, compared with 2.3%; P = 0.008). Strongyloidiasis had been found in 9.7% of all veterans, but in 15% of ex-POWs and in 19% of those who had worked on the Burma-Thailand railway. No other significant differences in gastrointestinal disease were found.

Protective action of endogenous opioid peptides of different origin against duodenal ulcer in rats

Calcium ionophore A23187 (10(-5) M) increases the force of contraction of the frog atrium up to 27 + 4.8%. The calcium antagonists d-600 (5 X 10- M), Zn2+ (2 X 10(-5) M), Mn2+ (2 X 10(-4) M) decrease the force of contraction 50, 10 and 20%, respectively, and inhibit the positive inotropic effect of ionophore A23187. Inhibition of the ionophore effect by the blockers is determined by the ability of D-600, Zn2+ and Mn2+ to form complexes with the ionophore. Besides, the affinity of these blockers to the ionophore is higher than that of Ca2+. It is assumed that Zn2+, Mn2+ and D-600 possess higher affinity to ionophore A23187 as compared with myocardial Ca-channels. Fenigidin interacts with Ca-channels to a larger degree than with ionophore A23187.

Healing of cysteamine-induced duodenal ulcers in the rat.

The mechanism and time for healing of cysteamine-induced duodenal ulcers in rats were investigated. Cysteamine induces a mixture of erosions, ulcers, and penetrating ulcers. These three stages of ulcerations healed in different ways and in different times. Erosions healed within three days by formation of new mucosa from the epithelium of the remaining parts of the crypts of Lieberkühn. The mucosa became completely normal within 15 days. Ulcers healed primarily by a contraction of the circular layer of the external muscle coat, thereby approaching the ulcer edges and reestablishing a complete layer of Brunner's glands in the submucosa. Healing was complete within 15 days. Penetrated ulcers healed very slowly by formation of new epithelium and Brunner's glands from the ulcer edges. The newly formed epithelium was desquamated unless protected by underlying Brunner's glands and the regeneration of these therefore determined the healing of the ulcer. Only a few of these ulcers had healed after 50 days. After 100 and 150 days, approximately 50% had healed, and after 200 days still only 64% had healed. Thus the cysteamine ulcer with destroyed muscle coat has a very prolonged healing and thereby represents a model for a chronic duodenal ulcer which may be of value as a model for testing treatments of duodenal ulcers.

O3F1048) - Functional Changes in the Early Phase of Cysteamine-Induced Duodenal Ulcers in Rats

O3F1048) - Functional Changes in the Early Phase of Cysteamine-Induced Duodenal Ulcers in Rats

Sex Differences in Peptic Ulcer Disease

As recently as 1968, twice as many men as women had peptic ulcer disease in the United States. To determine the current pattern of ulcer disease frequency in men and women, we examined data from the National Center for Health Statistics. These data show that the male predominance in peptic ulcer disease has changed. The male to female ratio is now 1.0 for self-reported period prevalence, and 1.3 for hospitalization and mortality. Ulcer prevalence rates for women have increased whereas rates for men have decreased. For hospitalizations and mortality, the changing sex ratios are primarily due to a more rapid decrease in duodenal ulcer rates for men than for women. Gastric ulcer hospitalizations for women have shown a marked increase for those greater than 65 yr old.

H2-blockers

Worldwide clinical experience has shown the short-term use of H2-blockers is safe and effective. They speed the healing of acute endoscopically proven duodenal ulcer with few important side effects. Curious differences in placebo response and reported efficacy from country to country deserve explanation, but do not blur the overall benefit from H2-blockers or the general satisfaction of patients and physicians. While it seems likely that a concerned physician and a dedicated patient could achieve the same results without such therapy, the major clinical advantage of H2-blockers lies in the speed and ease with which they relieve symptoms and hasten healing of the ulcer crater. Indeed, it could be argued that such therapy should not be restricted to the patient with a "proven" duodenal ulcer, and that patients with symptoms who might have "Moynihan's disease" (dyspepsia without a crater) deserve therapy without further diagnostic endeavors. Long-term therapy is still under judgment for both safety and efficacy. Controlled clinical trials suggest that H2-blockers prevent the recurrence of endoscopically proven duodenal ulcer at an impressive rate, while the recurrence rate of duodenal ulcer in patients taking placebo has been appalling. Many thoughtful physicians now argue that the patient with a duodenal ulcer ought to remain on maintenance therapy after the ulcer has healed. There is a problem, however, in the "selection" bias of the controlled trial; only patients with a proven ulcer crater have been entered into such studies and therefore they represent a subset, however important, of patients with dyspepsia and peptic ulcer symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of atropine, cimetidine and FPL 52694 on duodenal ulcers in mice

Cysteamine-induced duodenal ulcers were compared in rats and mice. Mice were slightly less sensitive to cysteamine ulcerogenesis than rats, but the ulcers were similar in location, histopathology and responses to drugs. Cysteamine treated mice rather than rats are advocated for screening purposes since less test compound is required. Atropine, 3–30 mg/kg orally, reduced the incidence, number, size and severity of duodenal ulcers in both species. Cimetidine, 300–500 mg/kg orally, reduced the size and number of ulcers in rats but was less effective on the incidence and severity of ulcers. 300 mg/kg orally reduced only ulcer size significantly in mice. FPL 52694, 300 mg/kg orally, reduced the incidence, number, size and severity of cysteamine-induced duodenal ulcers in rats and mice. The anti-ulcer activities of atropine, FPL 52694 and cimetidine are discussed in relation to their gastric anti-secretory actions.

Effects of antiulcer agents on healing of mepirizole-induced duodenal ulcers in rats.

Healing processes of duodenal ulcers induced by mepirizole and effects of several drugs on the ulcer healing were studied in rats. Mepirizole-induced duodenal ulcers, except for the perforated ones within 3 days after ulceration, gradually diminished in size and depth by the 15th day. Several ulcers persisted for up to 40 days, but complete healing in all rats occurred by the 60th day after ulceration. Oral cimetidine and YM-11170 (both histamine H2-receptor antagonists), at 200 and 30 mg/kg twice daily for 10 days, respectively, significantly accelerated the healing of duodenal ulcers. Oral Maalox (antacid) at 1,000 mg/kg thrice daily and propantheline (anticholinergic agent) at 30 mg/kg twice daily tended to accelerate the healing of the ulcers. Oral 16,16-dimethyl PGE2, at 0.03 and 0.1 mg/kg twice daily, resulted in a delayed healing of the ulcers. Mepirizole-induced duodenal ulcers appear to be a useful model for the study of ulcer healing and for screening of antiulcer drugs.

The effect of intracisternally administered bombesin on cysteamine-induced duodenal ulcers in rats

Cysteamine (420 mg/kg s.c.) increased gastric acid secretion in rats 3–6 h post-injection; duodenal pH fell from 6.0±0.2 (S.E.M.) at 0 time to 2.2.±0.3 at 12 h. A high (60–80%) incidence of duodenal ulcerations was observed 18 h after cysteamine injection. Intracisternal (i.c.) administration of bombesin (1 μg) significantly inhibited both cysteamine-induced increases in gastric acid secretion and the development of duodenal ulcers. The effect of bombesin was dose-dependent and appears to be relatively specific since i.c. neurotensin (1 or 30 μg) was not cytoprotective. Peripheral cholinergic (muscarinic) blockade with atropine methylbromide (10 mg/kg i.p.) was as effective as i.c. bombesin (1 μg) in inhibiting cysteamine-induced gastric hypersecretion and duodenal ulcers.

Effect of enkephalin and cimetidine on the onset and course of duodenal ulcers in rats

A study was made of the effect of a synthetic enkephalin analog and cimetidinee on experimental duodenal ulcer in rats induced by cysteamine administration. The ulcers were demonstrated to heal within 4 weeks. It was noted that ulcer occurrence was preceded by the increased serum gastrin level. Administration to rats of the enkephalin analog accelerated ulcer healing to a greater extent than that of cimetidin. It is suggested that one of the mechanisms of enkephalin analog protective action might involve the prevention of the gastrin increased level.

Duodenal pepsinogens in experimental duodenal ulcer in rats

Chemically induced duodenal ulcer in rats resembles the duodenal ulcer disease in humans. The mechanism of such an ulceration is not well established. This is an attempt to show that pepsinogens may play a role in such an ulceration. Twenty-four female Sprague-Dawley rats weighing 150–175 g each were divided into four groups of six rats each. The control group (A) was given 0.5 ml of distilled water subcutaneously and experimental groups were each given cysteamine (42.5 mg/100 g body wt of rats). The rats were sacrificed at 1, 2, and 4 hr. The pepsinogen content per milligram of protein was calculated in gastric and duodenal mucosa of all groups. Cysteamine produced a marked increase in duodenal mucosal pepsinogen level; however, gastric pepsinogen levels fell and were less than half at 4 hr. This might explain why cysteamine produced only duodenal ulcers and not gastric ulcers in this experimental model.