Oral Administration Of Indomethacin Research Articles

Unravelling the Gastroprotective Potential of Kefir: Exploring Antioxidant Effects in Preventing Gastric Ulcers.

The present study was conducted to evaluate the protective effect of milk kefir against NSAID-induced gastric ulcers. Male Swiss mice were divided into three groups: control (Vehicle; UHT milk at a dose of 0.3 mL/100 g), proton pump inhibitor (PPI; lansoprazole 30 mg/kg), and 4% milk kefir (Kefir; 0.3 mL/100 g). After 14 days of treatment, gastric ulcer was induced by oral administration of indomethacin (40 mg/kg). Reactive oxygen species (ROS), nitric oxide (NO), DNA content, cellular apoptosis, IL-10 and TNF-α levels, and myeloperoxidase (MPO) enzyme activity were determined. The interaction networks between NADPH oxidase 2 and kefir peptides 1-35 were determined using the Residue Interaction Network Generator (RING) webserver. Pretreatment with kefir for 14 days prevented gastric lesions. In addition, kefir administration reduced ROS production, DNA fragmentation, apoptosis, and TNF-α systemic levels. Simultaneously, kefir increased NO bioavailability in gastric cells and IL-10 systemic levels. A total of 35 kefir peptides showed affinity with NADPH oxidase 2. These findings suggest that the gastroprotective effect of kefir is due to its antioxidant and anti-inflammatory properties. Kefir could be a promising natural therapy for gastric ulcers, opening new perspectives for future research.

Recovery from indomethacin-induced gastrointestinal bleeding by treatment with teprenone

BackgroundGastrointestinal injuries caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is a serious side effect in patients with rheumatoid arthritis (RA). However, effective therapeutic strategies have yet to be established. In this study, we investigated the therapeutic effects of teprenone (TEP), a gastric mucosal protective drug, on NSAID-induced gastrointestinal injuries in rats with RA (AA rats).MethodsGastrointestinal injury was induced by oral administration of indomethacin (IMC), a typical NSAID. TEP was orally administered after IMC-induced gastrointestinal bleeding, and the stomach, jejunum, and ileum were excised.ResultsOn day 14 of IMC administration, lesion areas in the stomach, jejunum, and ileum were significantly larger in AA rats than in normal rats. When TEP was orally administered to AA rats, the lesion areas in the stomach, jejunum, and ileum significantly decreased compared with those in control rats (IMC-induced AA rats). Therefore, we measured NOS2 mRNA and NO levels, which were significantly decreased in rats with IMC-induced AA after treatment with TEP.ConclusionsThese results suggest that the oral administration of TEP may be useful for the treatment of NSAID-induced gastrointestinal injuries in patients with RA.

Gastro-protective Effect of Corn Diet against Indomethacin Induced Ulceration in Experimental Rats

Introduction: One of the most prevalent gastrointestinal ailments is gastric ulcer, which is caused by an imbalance between protective and aggressive factors. Zea mays Corn is a significant cereal crop containing natural phytochemical substances that are sources of nourishment. The methanolic extract of Corn, according to a previous study, lowers stomach acidity and inhibits the percentage of gastric ulceration with no knowledge on the mechanisms involved.
 Aim: This study investigated the underlying gastroprotective mechanisms of the Corn diet (ZD).
 Materials and Methods: Sixty male Wistar rats were used, randomly grouped into 6; 1(Normal control), 2(Ulcerated control), 3, 4, 5 (prefed with ZD -55%, 65%, 75%) and 6 (cimetidine- 25mg/kg) for 28 days. Gastric ulcer was induced by oral administration of indomethacin (40mg/kg) and animals were sacrificed after 4 hours. The stomach was excised and cleaned, it was then homogenized and centrifuged for biochemical assays.
 Results: There is a significant reduction in gastric ulcer area in all treated groups. Significant increase in gastric tissue mucin content and gastric mucosal SOD, NO and PGE2 levels and significant reduction in the MDA was observed in the ZD and cimetidine group. Histological evaluation showed tubular glands closely packed and separated from each other by laminar propia, however there is mild presence of inflammatory cells within the laminar propia in the ZD groups compared to ulcerated control group that showed moderate oedema with infiltration of inflammatory cells with mild vascular congestion in the mucosa. There is significant reduction in the macroscopic gastric mucosal lesions with percentage inhibition of 90%, 92%, 90% and 92% in the ZD (55%, 65% and 75%) and cimetidine group respectively.
 Conclusion: Results obtained from this study suggests that Zm diet may have anti-ulcerogenic properties by enhancing antioxidant enzymes as well as, nitric oxide and prostaglandin E2 mechanisms.

Antiulcer activity of hydroalcoholic extract of Bombacopsis glabra (Pasq.) A. Robyns. Leaves (Bombacaceae) in rat

The purpose of this study was to investigate the activity of the hydroalcoholic extract ofBombacopsis glabra leaves in rat. The mucoprotector effect of B. glabra leaves hydroalcoholic extract was studied by evaluating its ability to protect the mucosa from aggression of repeated oral administration of indomethacin at a dose of 30 mg/kg while pylorus ligature was used to study its anti-secretory effect. The results show that hydroalcoholic extract of the leaves of B. glabra, at doses 300 and 600mg/kg, decrease the surface area of lesions induced by indomethacin from 6.2 observed in the control group animals to 2.51 and 1.19 0.073 mm² respectively, in the treated animals (p 0.05). The extract decreases gastric acidity by increasing the pH of the gastric content from 1.7 0.03 of the control animals to 2.27 3.59 0.11 of the animals that received the extract at dose 300 and 600mg/kg respectively (p<0.05). These results show that the hydroalcoholic extract of B. glabra leaves possesses an anti-secretory effect and acts as a mucoprotector, and therefore has an antiulcer activity. The alkaloids, flavonoids, tannins, or polysaccharides in the extract could be responsible for this activity.

Evaluation of Gastro-protective Activity of Red-cabbage Against Indomethacin Induced Ulcer in Rats

Background and objective: The red cabbage (Brassica oleracea Linn var. capitata) is a leafy green biennial plant that contains beta-carotene, vitamin C and fibre. It is used in cooking for its nutritional value and has known anti-inflammatory activity.This study compared the antiulcerogenic activity of Aqueous Extract of Brassica (AEB) oleracea var. capitata with Misoprostol.Materials and Method: Acute gastric ulcers were induced in albino rats by the oral administration of indomethacin. The gastroprotective potential of the AEB(250,500 and 1000 mg/kg body weight) was compared with Misoprostol (100?g/kg body weight). Results:A significant reduction in the mean number of lesions was observed in high dose AEB (0.83 +/- 0.75) compared with indomethacin (4.00 +/- 1.26). Mean number of lesions were similar in misoprostol groups (1.50 +/- 0.55) and medium dose AEB (1.77 +/- 0.41).No significant reduction in the mean number of lesions was observed in low dose AEB (3.00 +/- 0.63) compared with indomethacin (4.00 +/- 1.26). Inhibition percentage was maximum in high dose AEB (97.71%) and minimum in low dose AEB (28.08%).Conclusions: The AEB demonstrated good antiulcerogenic activities which justify the inclusion of this plant in the management of gastric disorders. Further experiments are underway to determine which anti-ulcer mechanisms involved in gastroprotection.

Mucoprotective and Mast Cell Stabilization Activities of Chromium (D-Phenylalanine)3 in Indomethacin-Induced Chronic Enterocolitis in Rats: In vitro Anti-Cancer Activity Using Caco-2 Cell Line

Objective The current research work was intended to establish the positive effects of chromium complex CrD-phe3 in indomethacin induced chronic enterocolitis. Additionally Caco-2 was used to elucidate the anti-cancer property of the title compound.Methodology Oral administration of indomethacin 1.5 mgkg twice quotidian for fourteen days was done to induce chronic enterocolitis in rats. Pre-treatment with chromium complex 30 amp 60 mugkg p.o for three days before induction was done and this continued up to the end of the study. Macroscopic scoring of the stomach jejunum and ileum was done to analyze the extent of damage and inflammation. Mesenteric mast cell degranulation counts serum and ileum tissue biochemical estimations and histopathological analysis were carried out. MTT assay was performed to identify the cytotoxicity of Cr D-Phe3 using Caco-2 cells.Results Oral administration of CrD-phe3 displayed a substantial reduction in the elevated macroscopical scores oxidative-nitrative stress biochemical parameters and mast cell degranulation induced by chronic treatment of indomethacin. The protective effect of the chromium complex was also established through histological inspection of the ileum. Further treatment of the title complex resulted in Caco-2 cell viability reduction and exhibited IC50 722.40 mM.Conclusion The pragmatic usefulness of the chromium complex might be owed to its antioxidative anti-inflammation anti-allergic and mucoprotective properties. In addition the title complex exhibited anticolorectal cancer.nbsp

Gastroprotective Effect of Enteral Nutrition Formula in Mice Injected Subcutaneously with Indomethacin.

We have previously shown that two enteral nutrition formulas suppressed gastric lesions induced by the oral administration of indomethacin (IND) in mice. However, the mechanism of their protective effect is unknown. In this study, the effect of the two enteral nutrition formulas on gastric lesions induced by subcutaneous IND injection was investigated, with the objective of exploring the possibility that they may interact directly with IND in the gastrointestinal tract. Ten-week-old, male, ICR mice were fasted, then orally given either purified water, Mermed® One, or 2-fold diluted Terumeal® 2.0α as enteral nutrition formula (25 mL/kg). IND was injected subcutaneously at 20 mg/kg after 30 min, and the stomach was removed 6 h later and fixed in formalin. The number and area of lesions in the stomachs of mice given enteral nutrition formula was reduced to 56–89% and 34–61%, respectively, compared with the mice given purified water. The time courses of plasma IND concentrations were comparable among the three groups. These results suggested that the effect of these enteral nutrition formulas on gastric lesions did not originate from their direct interaction with IND in the gastrointestinal tract or their effect on the disposition of IND.

Protective effect of zinc and Pine barks extract supplement against Indometacin-induced gastric ulcer in rats

Abstract This investigation was aimed to study the effect of Pinus halepensis aqueous bark extract and zinc to prevent indomethacin induced gastric ulcer in rats. Thirty female albino Wistar rats were divided into 6 groups of 5 animals each (n=5); Group 1: normal control, Group 2: ulcer rats received normal saline, Group 3: ulcer rats treated with P. halepensis, Group 4: ulcer rats were treated with zinc, Group 5: ulcer rats were treated with P. halepensis + zinc and Group 6 ulcer rats were treated with Ranitidine for 15 days. Stomach ulcer was induced by a single oral administration of indomethacin (30 mg/kg). Various biochimical, physiologic and histologic parameters were estimated. Obtained results show that the ulcer index, pH and total acidity level were significantly reduced (p<0.05) and Pepsin activity was significantly increased (p< 0.05) in ulcer induced rats pre-treated with extract of P. halepensis, zinc and ranitidine when compared with indomethacin treated rats. The MDA level was significantly decreased and GSH level was increased (p< 0.05) in rats treated with plant extract and zinc. Histopathology of gastric mucosa confirmed the gastro-protection by plant and zinc treatment. The study reveals anti-ulcer and antioxidant properties were observed in bark aqueous extract of P. halepensis groups with a benefic effect of zinc to reduce oxidative stress and gastric ulcer induced in the rat.

Effect of Cuttlebone on Healing of Indomethacin-Induced Acute Gastric Mucosal Lesions in Rats.

The continuing use of nonsteroidal anti-inflammatory drugs (NSAIDs) usually increases the side effects such as peptic ulcer and acute gastric lesions in the gastrointestinal tract. Cuttlebone (CB), isolated from Sepiella maindroni de Rochebrune, was reported to have antioxidant activities, but its role in the treatment of indomethacin-induced gastric lesions has not yet been confirmed. In this research, we investigate the protective effect of cuttlebone on indomethacin-related ulcers in rats and possible mechanisms. Here, gastric ulcers were induced by oral administration of indomethacin, and then the rats were treated with omeprazole (4 mg/kg) or different doses (750, 1500, and 3000 mg/kg of body weight) of cuttlebone. We evaluated lesion index, inflammation score, and a series of oxidant/antioxidant parameters. The data demonstrated that cuttlebone could protect against gastric ulcers induced by indomethacin in a dose-dependent manner (positive correlation). Also, these effects were associated with attenuating the expression of malonaldehyde (MDA) and increasing the levels of some protective ingredients like epidermal growth factor (EGF), prostaglandin E2 (PGE2), and superoxide dismutase (SOD). Thus, considering its ability to protect indomethacin-induced acute gastric mucosal lesions and the underlying mechanisms, CB might be a potential candidate for treating gastric damage caused by NSAIDs.

Modeling undernutrition with enteropathy in mice

Undernutrition is a global health issue leading to 1 out 5 all deaths in children under 5 years. Undernutrition is often associated with environmental enteric dysfunction (EED), a syndrome associated with increased intestinal permeability and gut inflammation. We aimed to develop a novel murine model of undernutrition with these EED features. Post-weaning mice were fed with low-protein diet (LP) alone or combined with a gastrointestinal insult trigger (indomethacin or liposaccharides). Growth, intestinal permeability and inflammation were assessed. LP diet induced stunting and wasting in post-weaning mice but did not impact gut barrier. We therefore combined LP diet with a single administration of indomethacin or liposaccharides (LPS). Indomethacin increased fecal calprotectin production while LPS did not. To amplify indomethacin effects, we investigated its repeated administration in addition to LP diet and mice exhibited stunting and wasting with intestinal hyperpermeability and gut inflammation. The combination of 3-weeks LP diet with repeated oral indomethacin administration induced wasting, stunting and gut barrier dysfunction as observed in undernourished children with EED. As noninvasive methods for investigating gut function in undernourished children are scarce, the present pre-clinical model provides an affordable tool to attempt to elucidate pathophysiological processes involved in EED and to identify novel therapeutic strategies.

Glycomacropeptide Ameliorates Indomethacin-Induced Enteropathy in Rats by Modifying Intestinal Inflammation and Oxidative Stress.

Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy is considered a serious and increasing clinical problem without available treatment. Glycomacropeptide (GMP) is a 64-amino acid peptide derived from milk κ-casein with numerous biological activities. The aim of this study was to investigate the protective effect of GMP on NSAID enteropathy in rats. Enteropathy was induced by seven days oral indomethacin administration. Rats were orally GMP treated from seven days previous and during the establishment of the enteropathy model. Changes in metabolism, hematological and biochemical blood alterations, intestinal inflammation and oxidative damage were analyzed. Integrity barrier markers, macroscopic intestinal damage and survival rate were also evaluated. GMP treatment prevented anorexia and weight loss in animals. Furthermore, prophylaxis with GMP ameliorated the decline in hemoglobin, hematocrit, albumin and total protein levels. The treatment had no therapeutic efficacy on the decrease of occludin and mucin (MUC)-2 expression in intestinal tissue. However, GMP markedly decreased neutrophil infiltration, and CXCL1, interleukin-1β and inducible nitric oxide synthase expression. Nitric oxide production and lipid hydroperoxide level in the small intestine were also diminished. These beneficial effects were mirrored by preventing ulcer development and increasing animal survival. These results suggest that GMP may protect against NSAID enteropathy through anti-inflammatory and antioxidant properties.

Potential Protective Effects of Sildenafil and Moringa on Experimentally-induced Gastric Ulcer in Rats

BACKGROUND: Sildenafil and Moringa appear to have the ability to reduce the ulcerogenic effect of the drugs used to induce ulcers in rats. AIM: The present study was conducted to investigate the gastroprotective effects of sildenafil citrate, Moringa oleifera, which is an Indian plant, and their combination against an indomethacin-induced gastric ulcer in rats. MATERIALS AND METHODS: Gastric ulcers were induced by oral administration of indomethacin. Forty rats were used in the study, divided into 5 groups: Control Vehicle (Group 1), group 2 received indomethacin (100mg/kg) P.O., group 3 was pretreated with sildenafil (50mg/kg) P.O. and then received indomethacin, group 4 was pretreated with moringa leaf powder (200mg/kg) and then received indomethacin, group 5 received both sildenafil and moringa before administration of indomethacin. RESULTS: Indomethacin induced marked ulceration in the gastric mucosa and an increase in gastric acidity as compared to the vehicle control group. Furthermore, the indomethacin treated group exhibited increased activity of lipid peroxide (MDA) and the level of tumor necrosis factor-α (TNF-α) in tissues, while it induced a decreased content of nitric oxide (NO). Pretreatment with sildenafil and/or moringa significantly reduced the gastric acid secretion, ulcer score, tissue MDA and TNF-α contents and increased NO content compared with indomethacin alone. CONCLUSION: Both sildenafil and moringa have protective effects on the experimentally induced gastric ulcers.

Ratlarda İndometazinle Oluşturulan Gastrik Ülser Üzerine Silimarinin Koruyucu Etkileri

Silymarin is a natural antioxidant polyphenolic flavonoid structure, it has been reported to be effective against free radicals and reactive oxygen species. Indomethacin is a nonsteroidal anti-inflammatory drug and can promote ulcer in gastric tissue. The purpose of this study was to investigate the protective effects of silymarin on indomethacin-induced gastric ulcer model. Forty two male Wistar albino rats were divided into 6 groups (n=7); control, indomethacin, lansoprazole+indomethacin, silymarin (25, 50 and 100 mg/kg)+indomethacin group. Different doses of silymarin were administered by oral gavage and then gastric ulcers were induced by oral administration of indomethacin (25 mg/kg). Ulcer protective activity of silymarin was compared with lansoprazole (30 mg/kg). The rats were euthanized 6 h after indomethacin exposure. Activities of superoxide dismutase (SOD), catalase (CAT) and myeloperoxidase (MPO) as well as malondialdehyde (MDA) and glutathione (GSH) levels were determined in stomach tissue. Gastric tissue was also assessed in terms of macroscopic as ulcerative areas. As a result, 100 mg/kg silymarin was showed antiulceratif effects. The same dose of silymarin significantly decreased MDA level and MPO activity, and increased SOD activity and GSH level in stomach tissue. Silymarin might have a protective effect against indomethacin-induced gastric ulcer as well as oxidative stress in rat.

Management of patent ductus arteriosus in premature infants.

Closure of hemodynamically significant patent ductus arterios (HSPDA) is one of the most important questions in modern neonatal intensive care, especially for preterm babies. Long-term functioning of the hemodynamically significant arterial duct leads to a large number of complications in premature babies, such as: bronchopulmonary dysplasia, periventricular leucomalacia, intraventricular hemorrhage, retinopathy of the premature. To prevent all these complications, the PDA should be closed pharmacologically or surgically as soon as possible without any hesitation. COX inhibitors are commonly used nowa days. Ibuprofen and indomethacin show the equal efficacy and no significant adverse events. But some patients still need surgical treatment. The aim of the study was to determine the feasibility, effectiveness and safety of using various volumes of infusion in combination with COX inhibitors and to determine its effect on the timing of the closure of PDA. 91 premature infants with a gestational age of 26-31 weeks with manifestations of respiratory distress syndrome and НSPDA were studied retrospectively. Premies were divided into 2 groups. Research groups were representative as to gestational age, gender, and weight (1205.0±435.0 g). Therapy for PDA closure included the use of various volumes of restrictive or liberal infusion therapy (from 50 to 100 ml/kg/day) and COX inhibitors (indomethacin, ibuprofen). The volume of infusion therapy was limited in the first group. Preemies received 53.5±6.4 ml/kg/day on DOL1 and 2. From the third day urine excretion increased and the volume of infusion therapy also raised to 63.6±5.6 ml/kg/day, and on day 5 – to 89.7±6.8 ml/kg/day. In the second group there was no strict limitation of the volume of infusion therapy (especially in the first 5 days). Delayed period of PDA closure (on average from 14.55±0.56 DOL) was associated with absence of limitation of the infusion volume. In the first group, volume of infusion therapy was restricted in the first 5 days, and the closure of the ductus arteriosus occurred extremely early (on 2.35±0.48 DOL). COX inhibitors were prescribed according to the standard scheme: in the first 3 days indomethacin was administered orally in doses of 0.2/0.1/0.1 mg/kg/day. If the premature baby had symptoms of intestinal paresis ( this restricted oral administration of indomethacin), ibuprofen was prescribed in a three-day course in doses of 10/5/5 mg/kg/day intravenously or 20/10/10 mg/kg/day in rectal form. In all groups, standard PDA closure therapy was used. In the more remote periods (14 and 28 days), there was no fundamental difference in the volume of infusion in all groups. For early PDA closure limitation of infusion therapy in the first 3-5 days in combination with COX is principle.

Evaluation of Pumpkin (Cucurbita moschata) Pulp and Seeds Extracts on Gastrointestinal Ulcers Induced by Indomethacin in Rats

Peptic ulcer is considered to be one of the most common diseases especially in old age persons due to, the prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs).The present study was done to evaluate the protective and improvement effects of oral administration of each of pumpkin pulp and seed aqueous and ethanolic extracts on gastrointestinal ulcer lesions induced by oral administration of indomethacin in rats. The results showed that indomethacin induced ulceration and inflammations in stomach and small intestine in rats revealed by a significant elevation in xanthine oxidase (XO) and myeloperoxidase (MPO) activities. Moreover, a significant increase in neutrophils infiltration and lipid peroxidation were evidenced by significant increase in the levels of malondialdehyde (MDA), nitric oxide (NO) with decrease in catalase (CAT) activity and reduced glutathione (GSH) level. However, treatments with pumpkin pulp and / or seed extracts caused a significant decrease in the values of gastric volume, free and total acidity in all groups of rats after administration of pumpkin pulp and / or seeds oil extracts and a significant protective and improvement effects on gastrointestinal status was observed compared to indomethacin pathogenic group.

Selective serotonin reuptake inhibitor fluvoxamine ameliorates stress- and NSAID-induced peptic ulcer possibly by involving Hsp70.

Background Selective serotonin reuptake inhibitors (SSRIs) have recently become potential candidates for a new therapeutic approach to ulcer and gastric bleeding. Heat shock protein 70 (Hsp70) plays an important role in cellular resistance to nonsteroidal anti-inflammatory drugs (NSAIDs). However, there is lack of evidence that fluvoxamine recruits Hsp70 to affect stress-induced gastric ulcer. Therefore, we investigated the effect of fluvoxamine on NSAID- and stress-induced gastric ulcer and the possible involvement of Hsp70. Methods ICR mice were used in the study. Stress induction was made by the water-immersion-plus-restraint method. NSAID-induced gastric ulcer was produced by oral administration of indomethacin. Fluvoxamine was given orally 30 min before stress induction and indomethacin treatment. Results Stress and indomethacin treatment significantly increased the ulcer index and intraluminal bleeding score. Stress and indomethacin treatment also significantly increased the expression of Hsp70. Fluvoxamine significantly decreased the ulcer index and intraluminal bleeding in both ulcer models. Moreover, fluvoxamine further increased the expression of Hsp70 in the gastric tissue of stress- and indomethacin-treated mice. Conclusions Our results indicate that fluvoxamine may have a protective effect against stress- as well as NSAID-induced gastric ulcer. In addition, the present study suggests the possible involvement of Hsp70 in the amelioration of gastric ulcer by fluvoxamine.

In Vivo Imaging of the Intra- and Extracellular Redox Status in Rat Stomach with Indomethacin-Induced Gastric Ulcers Using Overhauser-Enhanced Magnetic Resonance Imaging.

Repeated use of nonsteroidal anti-inflammatory drugs can induce changes in the redox status, including production of reactive oxygen species (ROS), but the specific details of these changes remain unknown. Overhauser-enhanced magnetic resonance imaging (OMRI) has been used in vivo to monitor the redox status in several diseases and map tissue oxygen concentrations. We monitored the intra- and extracellular redox status in the stomach of rats with indomethacin-induced gastric ulcers using OMRI and investigated the relationship with gastric mucosal damage. One hour after oral administration of indomethacin (30 mg/kg), OMRI measurements in the stomach were made following nitroxyl probe administration. OMRI with the membrane-permeable nitroxyl probe, 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl (TEMPOL), demonstrated a redox change toward oxidation, which was reversed by a membrane-permeable antioxidant. Conversely, imaging with the impermeable probe, 4-trimethylammonium-2,2,6,6-tetramethyl-piperidine-1-oxyl (CAT-1), demonstrated little redox change. Redox imbalance imaging of a live rat stomach with indomethacin-induced gastric ulcers was produced by dual imaging of 15N-labeled TEMPOL and 14N-labeled CAT-1, in addition to imaging with another membrane-permeable 15N-labeled probe, 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl (MC-PROXYL), and 14N-labeled CAT-1. Pretreatment with MC-PROXYL suppressed gastric mucosal damage, whereas pretreatment with CAT-1 did not suppress ulcer formation. OMRI combined with a dual probe is a less invasive imaging technique for evaluation of intracellular ROS production contributing to the formation of gastric ulcers in the stomach of indomethacin-treated rats, which cannot be done with other methods. This method may be a very powerful tool for characterizing the pathogenesis of various diseases and may have medical applications.

Anti-ulcerogenic effect of the methanol extract of Chasmanthera dependens (Hochst) stem on male Wistar rats.

Background Oxidative stress and free radical-mediated processes have been implicated in the pathogenesis of indomethacin-induced gastric ulcer. This study investigated the ability of the methanol extract of Chasmanthera dependens to protect the gastric mucosal from oxidative damage induced by oral administration of indomethacin in rats. Methods The C. dependens stems were chopped into pieces, air-dried, and pulverized into powder. One kilogram of the powder was macerated in 1 L of methanol for 72 h. The mixture was filtered and evaporated using rotatory evaporator to obtain the extract of C. dependens. Adult male rats were divided into eight groups of six animals per group and were pretreated orally with the methanol extract of C. dependens (200, 400, and 800 mg/kg) or cimetidine (CIM), a standard drug (50 mg/kg), for 7 days. Gastric ulcer was induced orally with indomethacin. Ulcerogenic parameters, oxidative stress indices, and histopathological examination of the stomach were assessed to monitor the gastroprotective potential of C. dependens stem. Results Indomethacin caused severe gastric mucosa damage and significant reduction in the gastric mucosa antioxidant system with concomitant increase in the level of lipid peroxidation. Pretreatment with the methanol extract of C. dependens or CIM significantly reduced the formation of ulcer at the different doses administered. Similarly, pretreatments with the extract or CIM improved the antioxidant system, decreased acid output, lipid peroxidation, and improved the architecture of the gastric mucosa in ulcerated rats. Conclusions The results show the gastroprotective effect of the methanolic extract of C. dependens, which may be attributed to its antioxidant properties.

Combination therapy with polydeoxyribonucleotide and proton pump inhibitor enhances therapeutic effectiveness for gastric ulcer in rats

AimsThe main action of proton pump inhibitors (PPIs) is to inhibit gastric acid secretion, and PPIs are widely used to treat gastric ulcer (GU). However, if the action of promoting gastric mucosal regeneration is added, the effectiveness of GU treatment can be enhanced. Thus, in order to improve the therapeutic effect on GU, we tried to develop combination therapy promoting regeneration in injured tissue besides suppressing gastric acid secretion. Main methodsPolydeoxyribonucleotide (PDRN) was selected to evaluate tissue regeneration, and pantoprazole was chosen as one of the PPIs. GU was induced by oral administration of indomethacin once a day for 7 days. Rats in drug-administered groups were intraperitoneally injected with 100 μL normal saline, containing each drug at the indicated concentration, once a day for 14 days after inducing GU. Key findingsPDRN and PPI combination therapy potently improved tissue regeneration and inhibited production of pro-inflammatory cytokines. PDRN treatment with or without PPI increased the concentration of cyclic adenosine-3,5′-monophosphate (cAMP) and the ratio of phosphorylated cAMP response element-binding protein (p-CREB) to cAMP response element-binding protein (CREB). PDRN treatment with or without PPI also increased the expressions of vascular endothelial growth factor (VEGF) and adenosine A2A receptor. SignificancePDRN and PPI combination therapy showed more potent therapeutic effect on GU compared to the PDRN monotherapy or PPI monotherapy. The excellent therapeutic effect of PDRN and PPI combination therapy on GU appeared by promoting regeneration of damaged tissue as well as inhibiting gastric acid secretion.

Antiulcer and hepatoprotective effects of aqueous extract of Plantago ovata seed on indomethacin-ulcerated rats

BackgroundThe objective of the study was to investigate the protective effects of aqueous extract of Plantago ovata seed (AEPOS) on peptic ulcer induced by indomethacin (IND) in rats. MethodsRats (250-300 g) were divided into three groups (5 rats in each group). Gastric ulcer was induced by a single oral gavage of 48 mg/kg IND. The first group received only 5% sodium bicarbonate orally (5 ml/kg) whereas the control (IND) group received only single oral dose of 48 mg/kg IND. The third group was pretreated with an extract (100 mg/kg) for 4 days. At the end of the 4th day, rats were kept fasted for 24 h before administration of IND 48 mg/kg. The rats were sacrificed 4 h after oral administration of IND and their stomach and liver were fixed in formalin (10%) and sections of 5 mm in diameter were prepared. Histological and morphological characteristics of stomach and liver were assessed using hematoxylin and eosin (H&E) staining. ResultsAEPOS (100 mg/kg) showed a significant (p < 0.05) reduction in microscopic and macroscopic ulcer index as compared to the IND group. Histological analysis indicated that AEPOS has hepatoprotective effect and can prevent mucosa damage in stomach. ConclusionResults revealed that AEPOS has anti-ulcer and hepatoprotective effects.