Cysteamine-induced Duodenal Ulcers Research Articles

(-)-Fenchone Prevents Cysteamine-Induced Duodenal Ulcers and Accelerates Healing Promoting Re-Epithelialization of Gastric Ulcers in Rats via Antioxidant and Immunomodulatory Mechanisms.

(-)-Fenchone is a naturally occurring monoterpene found in the essential oils of Foeniculum vulgare Mill., Thuja occidentalis L., and Peumus boldus Molina. Pharmacological studies have reported its antinociceptive, antimicrobial, anti-inflammatory, antidiarrheal, and antioxidant activities. The preventive antiulcer effects of (-)-Fenchone were assessed through oral pretreatment in cysteamine-induced duodenal lesion models. Gastric healing, the underlying mechanisms, and toxicity after repeated doses were evaluated using the acetic acid-induced gastric ulcer rat model with oral treatment administered for 14 days. In the cysteamine-induced duodenal ulcer model, fenchone (37.5-300 mg/kg) significantly decreased the ulcer area and prevented lesion formation. In the acetic acid-induced ulcer model, fenchone (150 mg/kg) reduced (p < 0.001) ulcerative injury. These effects were associated with increased levels of reduced glutathione (GSH), superoxide dismutase (SOD), interleukin (IL)-10, and transforming growth factor-beta (TGF-β). Furthermore, treatment with (-)-Fenchone (150 mg/kg) significantly reduced (p < 0.001) malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and nuclear transcription factor kappa B (NF-κB). A 14-day oral toxicity investigation revealed no alterations in heart, liver, spleen, or kidney weight, nor in the biochemical and hematological parameters assessed. (-)-Fenchone protected animals from body weight loss while maintaining feed and water intake. (-)-Fenchone exhibits low toxicity, prevents duodenal ulcers, and enhances gastric healing activities. Antioxidant and immunomodulatory properties appear to be involved in its therapeutic effects.

From Selye's and Szabo's Cysteamine-Duodenal Ulcer in Rats to Dopamine in the Stomach: Therapy Significance and Possibilities.

We reviewed gastric ulcer healing by dopamine considering several distinctive duodenal key points. Selye and Szabo describe the cysteamine-induced duodenal ulcer in rats as a duodenal stress ulcer in patients. Szabo's cysteamine duodenal ulcer as the dopamine duodenal healing and cysteamine as a dopamine antagonist signifies the dopamine agonists anti-ulcer effect and dopamine antagonists ulcerogenic effect. From these viewpoints, we focused on dopamine and gastric ulcer healing. We mentioned antecedent studies on the dopamine presence in the stomach and gastric juice. Then we reviewed, in the timeline, therapy significance arising from the anti-ulcer potency of the various dopamine agonists, which is highly prevailing over the quite persistent beneficial evidence arising from the various dopamine antagonists. Meanwhile, the beneficial effects of several peptides (i.e., amylin, cholecystokinin, leptin, and stable gastric pentadecapeptide BPC 157, suggested as an acting mediator of the dopamine brain-gut axis) were included in the dopamine gastric ulcer story. We attempt to resolve dopamine agonists/antagonists issue with the dopamine significance in the stress (cysteamine as a prototype of the duodenal stress ulcer), and cytoprotection (cysteamine in small dose as a prototype of the cytoprotective agents; cysteamine duodenal ulcer in gastrectomized rats). Thereby, along with dopamine agonists' beneficial effects, in special circumstances, dopamine antagonists having their own ulcerogenic effect may act as "mild stress (or)" or "small irritant" counteracting subsequent strong alcohol or stress procedure-induced severe lesions in this particular tissue. Finally, in the conclusion, as a new improvement in further therapy, we emphasized the advantages of the dopamine agents' application in lower gastrointestinal tract therapy.

Role of Daucus carota in Enhancing Antiulcer Profile of Pantoprazole in Experimental Animals.

The carrot plant (Daucus carota) and its components are traditionally reported for the management of gastric ulcers. This study was performed to evaluate the role of carrot when administered concurrently with a conventional antiulcer treatment, pantoprazole, in alleviating gastric and duodenal ulcers in female experimental animals. The study involved standard animal models to determine the ulcer preventive effect using pylorus ligation, ethanol, and stress induced acute gastric ulcer models and duodenal ulcer models involving cysteamine. Acetic acid-induced chronic gastric ulcer and indomethacin-induced gastric ulcer models were used to evaluate the ulcer healing effect. Carrot fruit (500 mg/kg) and its co-administration with pantoprazole produced significant protection in an ethanol- and stress-induced acute gastric ulcer and cysteamine-induced duodenal ulcer. The healing of the acetic acid-induced chronic gastric ulcer was also augmented with this combination. Both total proteins and mucin contents were significantly increased in indomethacin-induced gastric ulcers. Similarly, in pylorus ligation, the pepsin content of gastric juice, total acidity, and free acidity were reduced. Overall, both ulcer preventive effects and ulcer healing properties of the pantoprazole were significantly enhanced in animals who received the co-administration of carrot fruit (500 mg/kg).

Pharmacological application of barium containing bioactive glass in gastro-duodenal ulcers

Peptic ulcer is prevalent in about 4% of the world population and nearly 10% of people have been affected by peptic ulcer at some point in their life. Therefore, there is a need for newer efficient and safe anti-ulcer agents. In the present strategy, we have prepared a novel bioactive glass containing 1.3 mol% of barium oxide (BaBG) and evaluated its antiulcer potential in gastroduodenal ulcer models. Prophylactic effect of BaBG pretreatment was evaluated for 5 days in ethanol, aspirin and pyloric ligation-induced gastric ulcer and cysteamine-induced duodenal ulcer models. Repeated treatment of 10 days of BaBG was evaluated in the healing ulcer model of acetic acid. BaBG significantly reduced the ulcerative damage against all the five tested ulcer models. Scanning electron microscope (SEM) images have shown that BaBG forms a physical protective barrier over the gastro-duodenal epithelium cell. In the pyloric-ligation, ethanol and aspirin models, BaBG showed significantly increased in gastric pH, indicating antacid like activity. BaBG treatment significantly increased cell proliferation in the pyloric model. Thus, BaBG mediates antiulcer action by forming a protective physical barrier against harsh luminal factors, acid neutralization and cell proliferation.

Anti-ulcerative, Anti-oxidative, and Anti-inflammatory Effects of Rosuvastatin and Isosorbide Dinitrate on Cysteamine-Induced Chronic Duodenal Ulcer in Rats

Anti-ulcerative, Anti-oxidative, and Anti-inflammatory Effects of Rosuvastatin and Isosorbide Dinitrate on Cysteamine-Induced Chronic Duodenal Ulcer in Rats

STAT3 and Importins Are Novel Mediators of Early Molecular and Cellular Responses in Experimental Duodenal Ulceration

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that directly upregulates VEGF, Ref-1, p21, and anti-apoptotic genes such as Bcl-xL. In this study, we hypothesized that STAT3 signaling is activated and provides a critical protective role that is required for enterocyte survival during the early phases of cysteamine-induced duodenal ulcers. We studied the effect of inhibition of STAT3 activity on cysteamine-induced duodenal ulcers in rats and egr-1 knockout mice using STAT3/DNA binding assay, immunohistochemistry, immunoblot, and quantitative reverse transcriptase PCR analyses. We found that G-quartet oligodeoxynucleotides T40214, a specific inhibitor of STAT3/DNA binding, aggravated cysteamine-induced duodenal ulcers in rats 2.8-fold (p<0.05). In the pre-ulcerogenic stage, cysteamine induced STAT3 tyrosine phosphorylation, its translocation to nuclei, an increased expression and nuclear translocation of importin α and β in the rat duodenal mucosa. Cysteamine enhanced the binding of STAT3 to its DNA consensus sequences at 6, 12, and 24h after cysteamine by 1.5-, 1.8-, and 3.5-fold, respectively, and activated the expression of STAT3 target genes such as VEGF, Bcl-xL, Ref-1, and STAT3-induced feedback inhibitor, a suppressor of cytokine signaling 3. We also demonstrated that egr-1 knockout mice, which are more susceptible to cysteamine-induced duodenal ulcers, had lower levels of STAT3 expression, its phosphorylation, expression of importin α or β, and STAT3/DNA binding than wild-type mice in response to cysteamine. Thus, STAT3 represents an important new molecular mechanism in experimental duodenal ulceration.

Anti-inflammatory and carbonic anhydrase restoring actions of yam powder (Dioscorea spp) contribute to the prevention of cysteamine-induced duodenal ulcer in a rat model

Increased acid output, accompanied with a defective defense system, is considered a fundamental pathogenesis of duodenal ulcer (DU). However, relapse of DU occurs despite proton pump inhibitors and H2 receptor antagonists, hence imposing the enforcement of the defense system. Dried powder of the yam tuber (Dioscorea spp) has been used in traditional folk medicine as a nutritional fortification. We hypothesized that dried-yam powder would prevent DU through improvement of anti-inflammatory actions and carbonic anhydrase (CA) activity. Therefore, we investigated the preventive effects of dried-yam powder against the cysteamine-induced DU and elucidated the underlying mechanisms. Duodenal ulcers were induced in Sprague-Dawley rats by intragastric administration of 500 mg/kg cysteamine-HCl. The dried-yam powder was used as a pretreatment before the cysteamine-HCl. The number and size of DU were measured. The expressions of inflammation mediators were checked in duodenal tissues, and the expressions of CAs and malondialdehyde levels were also examined. Cysteamine provoked perforated DU, whereas dried-yam powder significantly prevented DU as much as pantoprazole and significantly reduced the incidence of perforation. The messenger RNA expressions of cyclooxygenase-2 and inducible nitric oxide synthase were remarkably decreased in the yam group compared with the cysteamine group, and the serum levels of proinflammatory cytokines including interleukin-1β, interleukin-6, and tumor necrosis factor were significantly attenuated in the yam group. Cysteamine significantly decreased the expression of CAs, whereas yam treatment significantly preserved the expressions of CA IX, XII, and XIV. In conclusion, dried-yam powder exerts a significant protective effect against cysteamine-induced DU by lowering the activity of inflammatory cytokines and free radicals and restoring the activity of CAs, except in CA IV.

Early growth response‐1 in the pathogenesis of cysteamineinduced duodenal ulcer

We showed earlier that the immediate‐early gene &amp; its zinc finger transcription factor early growth response (Egr) product were enhanced, including the expression of target genes (e.g., bFGF, PDGF, VEGF) in early stage of cysteamine (C)‐induced DU. Our recent studies demonstrated that deletion of egr‐1 gene led to 4.4‐fold increase in C‐induced DU in egr‐1 knockout (KO) vs. wild‐type (WT) mice. mRNA expression of bFGF, VEGF &amp; PDGF was still increased but protein expression of bFGF, VEGF &amp; PDGF was diminished in egr‐1 KO mice. We hypothesized that specific miRNAs in egr‐1 KO mice might be activated &amp; inhibit protein synthesis of egr‐1 target genes. Using miRXplore Microarray study we found that 11 miRNAs (e.g., mir‐696, mir‐467E, mir‐152 &amp; mir‐301B) were elevated by 1.8‐ to 1.9‐fold in egr‐1 KO mice vs. WT mice. Mir‐1892 decreased by 1.7‐fold in egr‐1 KO vs. WT mice. These miRNAs partially share validated targets relating to growth factor responses, e.g., FGFR3 &amp; VEGF. We also demonstrated that DU was significantly reduced in rats treated with adenovirus encoding egr‐1 on days 7 &amp; 14 (p &lt; 0.05) respectively. The mRNA &amp; protein expressions of egr‐1, bFGF, VEGF &amp; PDGF markedly increased in rats after egr‐1 gene therapy. We conclude that Egr‐1 plays a preventive role in the pathogenesis of DU &amp; further studies are needed to identify miRNA expression in egr‐1 KO &amp; WT mice with DU.(This work was supported by the Veterans Health Administration Merit Review Grant to S. Szabo).

New mechanistic explanation for the localization of ulcers in the rat duodenum: Role of iron and selective uptake of cysteamine

Cysteamine, a coenzyme A metabolite, induces duodenal ulcers in rodents. Our recent studies showed that ulcer formation was aggravated by iron overload and diminished in iron deficiency. We hypothesized that cysteamine is selectively taken up in the duodenal mucosa, where iron absorption primarily occurs, and is transported by a carrier-mediated process. Here we report that cysteamine administration in rats leads to cysteamine accumulation in the proximal duodenum, where the highest concentration of iron in the gastrointestinal tract is found. In vitro, iron loading of intestinal epithelial cells (IEC-6) accelerated reactive oxygen species (ROS) production and increased [14C]cysteamine uptake. [14C]Cysteamine uptake by isolated gastrointestinal mucosal cells and by IEC-6 was pH-dependent and inhibited by unlabeled cysteamine. The uptake of [14C]cysteamine by IEC-6 was Na+-independent, saturable, inhibited by structural analogs, H2-histamine receptor antagonists, and organic cation transporter (OCT) inhibitors. OCT1 mRNA was markedly expressed in the rat duodenum and in IEC-6, and transfection of IEC-6 with OCT1 siRNA decreased OCT1 mRNA expression and inhibited [14C]cysteamine uptake. Cysteamine-induced duodenal ulcers were decreased in OCT1/2 knockout mice. These studies provide new insights into the mechanism of cysteamine absorption and demonstrate that intracellular iron plays a critical role in cysteamine uptake and in experimental duodenal ulcerogenesis.

Attenuation of cysteamine‐induced duodenal ulcer with Cochinchina momordica seed extract through inhibiting cytoplasmic phospholipase A2/5‐lipoxygenase and activating γ‐glutamylcysteine synthetase

Cysteamine is a reducing aminothiol used for inducing duodenal ulcer through mechanisms of oxidative stress related to thiol-derived H(2)O(2) reaction. Cochinchina momordica saponins have been suggested to be protective against various gastric diseases based on their cytoprotective and anti-inflammatory mechanisms. This study was aimed to document the preventive effects of Cochinchina momordica seed extract against cysteamine-induced duodenal ulcer as well as the elucidation of its pharmacological mechanisms. Cochinchina momordica seed extract (50, 100, 200 mg/kg) was administrated intragastrically before cysteamine administration, after which the incidence of the duodenal ulcer, ulcer size, serum gastrin level, and the ratio of reduced glutathione (GSH)/oxidized glutathione disulfide (GSSG) as well as biochemical and molecular measurements of cytoplasmic phospholipase A(2) (cPLA(2)), cyclooxygenase-2 (COX-2), 5-lipoxygenase and the expression of proinflammatory genes including IL-1β, IL-6, COX-2 were measured in rat model. Additional experiments of electron spin resonance measurement and the changes of glutathione were performed. Cochinchina momordica seed extract effectively prevented cysteamine-induced duodenal ulcer in a dose-dependent manner as reflected with significant decreases in either duodenal ulcerogenesis or perforation accompanied with significantly decreased in serum gastrin in addition to inflammatory mediators including cPLA(2), COX-2, and 5-lipoxygenase. Cochinchina momordica seed extract induced the expression of γ-glutamylcysteine synthetase (γ-GCS)-related glutathione synthesis as well as significantly reduced the expression of cPLA(2). Cochinchina momordica seed extract preserved reduced glutathione through increased expressions of γ-GCS. Cochinchina momordica seed extracts exerted significantly protective effect against cysteamine-induced duodenal ulcer by either cPLA2 inhibition or glutathione preservation.

Antiulcer Activity of Lemon (Citrus limon) Fruit Juice and Its Interaction with Conventionally used Antiulcer Drugs in Rats

Lemon (Citrus limon) fruit is used for culinary and non-culinary purposes throughout the world. In traditional medicine, lemon fruit juice is used as home remedy for a variety of gastrointestinal disorders. This study evaluates the effect of lemon juice on gastric and duodenal ulcers and determines its interaction with conventionally used antiulcer drugs; pantoprazole and ranitidine. The antiulcer activity of lemon juice at two different doses and its interaction antiulcer agents was evaluated in acetic acid induced chronic gastric ulcer, pylorus ligation induced gastric ulcer, ethanol induced gastric ulcer, stress induced gastric ulcer, indomethacin induced gastric ulcer and cysteamine induced duodenal ulcer models. In all these models, the common parameter determined was ulcer index. The lemon juice produced marginal ulcer healing effect and augmented the ulcer healing effect of pantoprazole and ranitidine in acetic acid induced chronic gastric ulcers, while in pylorus ligated rats, lemon juice demonstrated gastric antisecretory and antiulcer effect. Both doses of lemon juice also showed significant antiulcer effect in ethanol induced, stress induced and indomethacin induced gastric ulcers. The lemon juice also reduced ulcer area in cysteamine-induced duodenal ulcer. Lemon juice possesses dose dependent antiulcer effect and augments the antiulcer action pantoprazole and ranitidine in rats. Keywords: Lemon juice, duodenal ulcer, gastric cytoprotection, gastric ulcer, gastric secretion, citrus, ranitidine, pantoprazole, rats, antiulcer action

Evaluation of Antiulcer Potential of Mimusops hexandra in Experimental Gastro Duodenal Ulcers

The study was aimed to investigate antiulcer effects of acetone extract and its different fractions Mimusops hexandra against experimental gastro-duodenal ulcers. 80% acetone extract of stem bark of Mimusops hexandra (Extract A, p.o.) and its different fractions namely diethyl ether (Extract A1, p.o.), ethyl acetate (Extract A2, p.o.) and aqueous (Extract A3, p.o.) were tested for the presence of preliminary phytoconstituents and were screened for their antiulcer potential in experimental animals using ethanol-HCl and aspirin-induced gastric damage at the dose of 500 mg kg-1p.o. Extract A2 being the most active fraction amongst all the fractions tested was also studied at different doses to find its ED50. Further, to establish the mechanism of action, Extract A2 was also tested for its effects in acetic acid-induced gastric ulcer models and cysteamine-induced duodenal ulcer. The effect was compared with cimetidine. Flavonoids (quercetin), procyanidins, saponins and triterpenoids were found to be present in bark. Oral administration of Extract A2 inhibited formation of gastric lesions induced by aspirin in a dose dependent manner. Elevated level of lipid peroxidation due to ethanol-HCl and aspirin induced gastric damage was significantly (p<0.05) reduced by the treatment with Extract A2. Further, Extract A2 at the dose of 100 mg kg-1 (p.o.) reduced extent of acetic acid induced gastric ulcer in experimental animals. Moreover, protection afforded by Extract A2 against cysteamine-induced duodenal lesions was evident from dose dependent decrease in ulcer index (p<0.05), score for intensity (p<0.05) and total lesion area (p<0.05), when compared with the control group. The antiulcer activity shown by Extract A2 in experimental gastro-duodenal ulcer could be attributed to decrease in gastric acid secretory activity along with strengthening of mucosal defensive mechanisms.

Antiulcer Activity of Patol Churna against Experimental Gastro-duodenal Ulcers in Rats

Patol churna is a well known ayurvedic formulation of Trichosanthes cucumerina Linn. (cucurbitaceae) administered in case of number of alimentary and liver disorders. It is widely used in Indian folk medicine for variety of disease conditions. The aim of present study was to evaluate the antiulcer activity of 50% ethanolic extract of patol churna (PCE) using various experimental models of gastric and duodenal ulceration in rats. Oral administration of 50% ethanolic extract of patol churna was evaluated in rats against ethanol, aspirin and pylorus ligated gastric ulcers as well as cysteamine-induced duodenal ulcers. In all the models studied, the antiulcer activity of PCE compared with that of cimetidine (100mg/kg, p.o.), an H 2 receptor antagonist. PCE showed significant antiulcer activity in ethanol-induced and aspirin-induced gastric ulcer models. In 19 hrs pylorus ligated rats, significant reduction in ulcer index, total acidity and pepsin activity was observed with PCE, when compared with the control group. Mucosal defensive factors such as pH, mucin activity and gastric wall mucous content was found to be increased with PCE. PCE was also, afforded remarkable protection in cysteamine-induced duodenal lesions. The antiulcer activity of PCE was comparable with that of cimetidine. Thus, patol churna extract possess significant antiulcer activity against both gastric and duodenal ulcers in rats. The antiulcer activity may be attributed to its cytoprotective action and inhibition of acid secretary parameters

Ghrelin accelerates the healing of cysteamine-induced duodenal ulcers in rats

SummaryBackgroundPrevious studies have shown that administration of ghrelin exhibits protective and therapeutic effects in the gut. The aim of the present investigation was to examine the influence of ghrelin administration on the course of cysteamine-induced duodenal ulcers, as well as effects on mucosal production of oxygen free radicals and duodenal antioxidant defense.Material/MethodsDuodenal ulcers were induced in male Wistar rats by cysteamine administered intragastrically at the dose of 200 mg/kg in 1 ml of saline, 3 times at 4-h intervals. Starting 24 h after the first dose of cysteamine, rats were treated intraperitoneally twice a day with saline or ghrelin given at the dose of 4, 8 or 16 nmol/kg/dose. Seven days after administration of the first dose of cysteamine, the study was terminated.ResultsInduction of ulcers by cysteamine was accompanied by a reduction in duodenal blood flow, mucosal DNA synthesis and mucosal activity of superoxide dismutase (SOD); whereas mucosal concentration of interleukin-1β and malonyldialdehyde (MDA – an index of lipid peroxidation) were increased. Treatment with ghrelin increased healing rate of duodenal ulcers and enhanced duodenal blood flow, mucosal DNA synthesis and mucosal activity of SOD, and reduced mucosal concentration of interleukin-1β and MDA.ConclusionsTreatment with ghrelin increases the healing rate of duodenal ulcers and this effect is related, at least in part, to improvement of duodenal mucosal blood flow, mucosal cell proliferation and antioxidant defense, as well as being related to reduction in mucosal oxidative stress and inflammatory response.

Cytoprotective Effect ofMorinda tinctoriaRoxb. against Surgical and Chemical Factor Induced Gastric and Duodenal Ulcers in Rats

The present paper relates to the pharmacological validation of the antiulcer efficacy of ethanol leaf extract ofMorinda tinctoriaRoxb. (EEMT) against aspirin pyloric ligation-induced gastric ulcer model and cysteamine-induced duodenal ulcer in Wistar rats. Oral administration of EEMT at a dose of 200 and 400 mg/kg significantly prevented the occurrence of aspirin pyloric ligation and cysteamine-induced gastric and duodenal ulceration. The volume and acidity of gastric juice in pyloric ligated rats were significantly () reduced by EEMT. There was a significant decrease in the number of ulcers, and its severity in both the models proved the ulcer protective activity of EEMT. Administration of extract at both dose levels has shown a significant increase in potassium and sodium ion concentration in the gastric juice of pylorus ligation group. On the basis of these observations, we concluded that EEMT possessing antiulcer activity may be due to the modulation of defensive factors by improvement in gastric cytoprotection.

Effect of andrographolide on cysteamine-induced duodenal ulcer in rats

The aim of this study was to evaluate the gastroprotective efficacy of andrographolide isolated from Andrographis paniculata in rats induced with duodenal ulcers. Duodenal ulcers were induced by cysteamine administration in rats pretreated with 3 mg kg−1 BW day−1 of andrographolide for 30 days. Ulcer score, myeloperoxidase activity, TBARS level, GSH/GSSG ratio and enzyme antioxidants were measured in the duodenal tissue. Brush border and basolateral membranes were isolated to assay sucrase, maltase, alkaline phosphatase and total ATPases. Ulcer score was significantly minimised in rats pretreated with andrographolide. Elevation in myeloperoxidase and TBARS levels were found to be minimised significantly due to andrographolide treatment. Membrane-bound enzyme activities and the thiol redox status of glutathione were significantly maintained in duodenal mucosa of rats that received andrographolide. This study reveals that the major component of A. paniculata, andrographolide, has potent antiulcer properties that are most likely caused by minimising inflammatory changes, counteracting free radical formation and maintaining the thiol redox status in the duodenum.

Inhibition of Cysteamine-Induced Duodenal Ulcers in OCT1/2 Knockout Mice

COX-2 and CGRP, downregulation of SOD but no effect on proinflammatory cytokines was observed. In rats with deactivated sensory nerves, the protective effect of orexin on the gastric mucosa against ethanol induced lesions was attenuated. This was associated with decreased expression of HSP70 and increase of COX-2 and SOD. No changes in proinflammatory cytokines were observed. In addition, orexin treatment caused a significant upregulation of CGRP expression. Conclusion: Orexin-A protects the gastric mucosa from acute lesions induced by 75% ethanol and this protective effect is mediated at least in part by sensory nerves and CGRP and stimulatory effect of this peptide on expression of HSP70 and the anti-oxidant enzyme SOD.

2,3‐Dimercaptopropanol, a thiol chelator, alleviates gastroduodenal ulcers in rats

Earlier studies have implicated reactive oxygen species and transitional metals in the pathogenesis of gastric lesions. In this study, we have evaluated the effect of 2,3-dimercaptopropanol (DMP), a thiol compound and metal chelator, on chemically induced gastroduodenal ulcers in rats. Acid secretion studies were undertaken using pylorus-ligated rats pretreated with DMP (3-100 mg/kg, i.p.). The effect of orally administered DMP on cysteamine-induced duodenal ulcers and ethanol-induced gastric ulcers was also tested. The level of nonprotein sulfhydryls (NP-SH) and gastric wall mucus was measured in the glandular stomach of rats treated with ethanol. None of the dose of DMP affected the volume or acidity of gastric secretion. Low doses of DMP (3 and 10 mg/kg) significantly reduced cysteamine-induced duodenal ulcers, whereas the high doses (30 and 100 mg/kg) were ineffective in this model. All the doses of DMP significantly and dose dependently attenuated ethanol-induced gastric lesions. The adverse effects of ethanol on gastric wall mucus and NP-SH were significantly and dose dependently reversed by DMP. In conclusion, the protective effects of DMP appear to be independent of gastric acid secretion and may be associated with counteracting the oxidative stress by replenishing glutathione and reducing the pool of transition metals.

Pharmacological efficacy of argemone mexicana plant extract, against cysteamine-induced duodenal ulceration in rats

The plant Argemone mexicana is traditionally used as diuretic, anti-inflammatory, antibacterial, antifungal agent, and has wound-healing property. This study was carried out to evaluate the effect of A. mexicana aerial part of the plant (methanolic and aqueous extract p.o.) on duodenal ulceration. The study was carried out on the duodenal ulceration model by using cysteamine hydrochloride. Ranitidine (20 mg/kg) was used as standard drug. Both the extracts of the plant A. mexicana produced a significant activity in cysteamine-induced duodenal ulceration. The aqueous extract at the dose-dependent manner showed the potent activity than methanolic extract. The plant A. mexicana Linn. Increased healing of gastric ulceration and prevented the development of experimentally induced duodenal ulceration in rats.

Effects of captopril on the cysteamine-induced duodenal ulcer in the rat

Oxidative stress is important factor underlying in a variety of diseases. Antioxidative enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) are part of the physiological defenses against oxidative stress. Malondialdehyde (MDA) is a lipid peroxidation biomarker and its elevated level in various diseases is related to free radical damage. Cysteamine is a cytotoxic agent, acting through generation of reactive oxygen species (ROS) and may decrease defense activity of antioxidative enzymes against ROS and induce duodenal ulcer. Captopril, acts as free radical scavengers and protect against injuries from oxidative damage to tissues.The aim of this study was the evaluation of the effect of captopril against cysteamine-induced duodenal ulcer by determining duodenal damage, duodenal tissue SOD and GSH-PX activities and plasma MAD level. This study was performed on 3 groups of 7 rats each: saline, cysteamine and cysteamine plus captopril treated groups. The effect of captopril against cysteamine-induced duodenal ulcer is determined by evaluating the duodenal damage, duodenal tissue SOD and GSH-PX activities and plasma MDA level. All animals were euthanized 24h after the last treatment and 2 ml blood and duodena samples were collected for calculation of ulcer index, histopathological assessment and measurement of tissue SOD, GSH-PX activities and plasma MDA level. Cysteamine produced severe duodenal damage, decreased the activity of duodenal tissue SOD and GSH-PX and increased the plasma MDA level compared with saline pretreated rats. Pretreatment with captopril decreased the cysteamine-induced duodenal damage and plasma level of MDA and increased the activities of SOD and GSH-PX in duodenal tissue compared with cysteamine pretreated animal. Our results suggest that captopril protects against cysteamine-induced duodenal ulcer and inhibits the decrease in SOD and GSH-PX activities and lipid peroxidation by increasing antioxidant defenses.