Induction Of Gastric Lesions Research Articles

Investigating the pharmacological potential of phytol on experimental models of gastric ulcer in rats.

Phytol is a diterpene constituent of many essential oils, belonging to the group of unsaturated acyclic alcohols. Although phytol possesses antimycobacterial and anti-inflammatory effects, no reports of a gastrointestinal action are available from the literature. Due to the well-known shortcomings of classical anti-ulcer drugs (e.g. side effects or relapses), natural products may offer an attractive alternative. In this study, a potential gastroprotective activity of phytol was evaluated using acute and chronic ulcer models in rats. Phytol 12.5, 25 and 50mg/kg, administered orally 1h prior to induction of gastric lesions by absolute ethanol, inhibited the lesion area by 96, 90 and 95%, respectively. When lesions were induced by ischemia and reperfusion, phytol 12.5 and 25mg/kg per os decreased the lesion areas by 89 and 46%, respectively. In the third acute ulcer model (lesions induced by ibuprofen), phytol 12.5mg/kg reduced the lesion area by 55%. Phytol restored the decreased level of reduced glutathione, the increased levels of myeloperoxidase and malondialdehyde and the decreased levels of catalase and superoxide dismutase in rats with gastric ulcer induced by ethanol to levels obtained in vehicle group. Finally, in a chronic model in which gastric ulcer was induced by acetic acid directly instilled into the stomach, phytol administered orally over a time period of 7 days at 12.5, 25, 50 and 100mg/kg reduced lesion areas by 84, 81, 83 and 68%. Our data suggest a gastroprotective and cicatrizing effect of phytol, possibly associated with its antioxidant effect.

Cytoprotective and antisecretory properties of methanolic extract of Distemonanthus benthamianus (Caesalpiniaceae) stem bark on acute gastric ulcer in rats.

In African traditional medicine, Distemonanthus benthamianus (Caesalpiniaceae) is used to treat many diseases including gastric ulcers. We evaluated in this study, the cytoprotective and antisecretory properties of the methanolic extract of the stem bark of this plant using different technics of gastric lesion induction. Cytoprotective and antisecretory activity of the methanolic extract of D. benthamianus stem bark was evolved through six methods of gastric lesion induction in experimental Wistar male rats (150-200g): (1) gastric lesions induced by HCl/ethanol, (2) gastric lesions induced by Indomethacin- HCl/ethanol, (3) gastric lesion induced by Indomethacin, (4) gastric lesions induced by Pylorus ligation, (5) gastric lesions induced by histamine-Pylorus ligation, (6) gastric lesions induced by carbachol-Pylorus ligation. Mucus and gastric mucosal ulceration were evaluated. pH, gastric volume, and acidity were quantified in all pylorus ligation induction technics. Nitric oxide (NO) level was determined in indomethacin induced gastric ulcers. At different doses (125, 250 and 500mg/kg), extract reduced significantly the ulcer index. In all models used, that is 100.00% with HCl/ethanol; 100.00% with HCl/ethanol/indomethacin; 95.70% with Indomethacin; 74.79% with pylorus ligation, 95.94% histamine-Pylorus ligation, 99.54% carbachol-Pylorus ligation at the highest dose of 500mg/kg. The lesion formation reduces in all the methods used followed by a significant increase of mucus production. The pylorus ligation technic revealed that the extract has an antisecretory activity. The methanolic extract of D. benthamianus stem bark has both cytoprotective and antisecretory effects. This extract exerts its antisecretory effect trough cholinergic and histaminergic pathways.

Inhibition of GKN2 Attenuates Acute Gastric Lesions Through the NLRP3 Inflammasome.

Objective: Acute gastric lesions are commonly seen in critically ill patients in the intensive care unit and can result in significant upper gastrointestinal bleeding. However, the signaling mechanisms that regulate this severe disease are still unclear. In this study, we explored the involvement of gastrokine 2 (GKN2) in the development of acute gastric lesions in mice. Approach: We measured the degree of injury using the water immersion restraint stress mouse model. Inflammatory cells and factors were analyzed after gastric lesion induction. The luciferase reporter assay was used to detect the transcription activity of nuclear receptor subfamily 3 group C member 1 (NR3C1) in regulation of GKN2. We also detected the downstream pathway of GKN2 in gastric lesions. Results: The results showed that GKN2 could aggravate stress-induced gastric lesions and gastric mucosal cell death. Moreover, the gastric lesion promoted by GKN2 was gastric acid independent. GKN2 could recruit neutrophils and promote the release of inflammatory factors to contribute to inflammation. NR3C1, activated by cortisol under stress, could act as a transcription factor to upregulate the expression of GKN2. Innovation: This study elucidates the process of gastric lesion at a molecular level and explores the possible contender biomarkers for diagnosis and drug targets in wound healing of gastric lesions. Conclusion: In conclusion, GKN2, which was upregulated by cortisol, aggravated the gastric lesion through activation of the inflammasome and inflammatory reaction.

Evaluation of the antioxidant and gastroprotective activity and HPLC analysis of the hydroalcoholic extract of Tocoyena formosa leaves (Cham. & Schlecht) K. Schum

The peptic ulcer is a gastric disorder that affects millions of people and yet they cause many side effects. In this sense, natural products represent an important alternative to the discovery of compounds with gastroprotective activity. The present work has as its objective to evaluate the antioxidant and gastroprotective activity of the Hydroalcoholic Extract of Leaves from Tocoyena formosa (Cham. & Schlecht.) K. Schum (HELTF), this being much emphasized in traditional medicine for inflammatory morbidities and gastric symptoms. For the evaluation of the antioxidant activity, FRAP and DPPH tests were carried out, and for the evaluation of the gastroprotective activity, gastric lesion induction by ethanol, acidified ethanol, indomethacin and physical barrier tests were used. Antioxidant assay of HELTF revealed an EC50 of 558.66 μM FeSO4/g and IC50 of 189.78 μg/ml for FRAP and DPPH respectively. In gastroprotective, in ethanol model, all the doses presented significant activity in comparison to controls, however, in the gastric lesion induction test by acidified ethanol and indomethacin, only the dose of 200 mg/kg presented with significance. In the physical barrier test presented evidence that protection by the formation of a protective layer associated with mucus. Concluded, therefore, that HELTF possesses antioxidant and significate gastroprotective activity.

Protective effects of vitamin B6 alone and in combination with L-cysteine and NaHS on ethanol and indomethacin-induced gastric lesions in mice.

This study was undertaken to investigate the protective effects of vitamin B6, cofactor for cystathionine-γ lyase and cystathionine-β synthase (producers of H2S), alone and in combination with L-cysteine, H2S precursor, on indomethacin-, and ethanol-induced gastric lesions in male NMRI mice. Fasted male NMRI mice were randomly assigned into 12 groups (7 in each). The gastroprotective activity of vitamin B6 alone and in combination with L-cysteine and sodium hydrosulfate (NaHS) was evaluated against ethanol-, and indomethacin-induced gastric lesions. The animals were received vehicle, vitamin B6, L-cysteine, L-cysteine+vitamin B6, NaHS or NaHS+B6 before the induction of gastric lesions by ethanol (50%, 0.5 ml/25 g of body weight, orally) or indomethacin (40 mg/kg, orally). One and five hours after the administration of ethanol and indomethacin, respectively, the animals were sacrificed using anesthetics. The stomachs were removed, rinsed with normal saline and assessed for gastric wall mucus changes. Pretreatment with L-cysteine, sodium hydrosulfate, and vitamin B6 significantly decreased the total area of gastric lesions (P<0.01). The mucus production in L-cysteine-, sodium hydrosulfate-, and vitamin B6-treated animals were significantly higher than in control rats P<0.05). The gastroprotective activity of L-cysteine and sodium hydrosulfate in combination with vitamin B6 were higher than when administered alone (P<0.05). The result of this survey showed that the protective activity of L-cysteine and sodium hydrosulfate enhances in the presence of vitamin B6.

THE EFFECTS OF HYDROGEN PEROXIDE (6%) IN GASTRIC MUCOSA â “ AN EXPERIMENTAL STUDY

The tooth whitening therapeutics can be performed at the clinic or ambulatory, with a greatest danger of eating the products of bleaching.This experimental study analysis the effect of these products on gastric mucosa with or without non‐tumor pathology. We used 50 mice Wistar‐Han. In periods II and III, which took place on 2nd and 3rd weeks, the animals in groups II, III, IV and V were subjected to induction protocol not gastric tumor by administering a chemical compound (50% ethanol), and/or administration of a 6% hydrogen peroxide bleaching agent (Colgate®Visible White™), by gavage.From the data collected were made statistical analysis of variance (ANOVA) and multiple comparison of pairs of means over time in a study by a t Student test. It was also performed a frequency analysis of the results of macroscopic observation of the gastric mucosa (JMP Version 7, SAS Institute Inc., NC, USA).There was a decrease in body weight in animals of groups handled during the study period, which was most pronounced in groups IV and V‐A. Changes in the spleen weight relative to body weight revealed no statistically significant changes. The gastric mucosa revealed in all groups manipulated lesions, which were more frequent in groups III and IV.We can conclude that there seems to be some signs of toxicity in 3 to 4 days after administration of hydrogen peroxide 6%, and induction of gastric lesions and generalized moderate.

Anti-inflammatory, gastroprotective and anti-ulcerogenic effects of red algae Gracilaria changii (Gracilariales, Rhodophyta) extract

BackgroundGracilaria changii (Xia et Abbott) Abbott, Zhang et Xia, a red algae commonly found in the coastal areas of Malaysia is traditionally used for foods and for the treatment of various ailments including inflammation and gastric ailments. The aim of the study was to investigate anti-inflammatory, gastroprotective and anti-ulcerogenic activities of a mass spectrometry standardized methanolic extract of Gracilaria changii.MethodsMethanolic extract of Gracilaria changii (MeOHGCM6 extract) was prepared and standardized using mass spectrometry (MS). Anti-inflammatory activities of MeOHGCM6 extract were examined by treating U937 cells during its differentiation with 10 μg/ml MeOHGCM6 extract. Tumour necrosis factors-α (TNF-α) response level and TNF-α and interleukin-6 (IL-6) gene expression were monitored and compared to that treated by 10 nM betamethasone, an anti-inflammatory drug. Gastroprotective and anti-ulcerogenic activities of MeOHGCM6 extract were examined by feeding rats with MeOHGCM6 extract ranging from 2.5 to 500 mg/kg body weight (b.w.) following induction of gastric lesions. Production of mucus and gastric juice, pH of the gastric juice and non-protein sulfhydryls (NP-SH) levels were determined and compared to that fed by 20 mg/kg b.w. omeprazole (OMP), a known anti-ulcer drug.ResultsMS/MS analysis of the MeOHGCM6 extracts revealed the presence of methyl 10-hydroxyphaeophorbide a and 10-hydroxypheophytin a, known chlorophyll proteins and several unidentified molecules. Treatment with 10 μg/ml MeOHGCM6 extract during differentiation of U937 cells significantly inhibited TNF-α response level and TNF-α and IL-6 gene expression. The inhibitory effect was comparable to that of betamethasone. No cytotoxic effects were recorded for cells treated with the 10 μg/ml MeOHGCM6 extract. Rats fed with MeOHGCM6 extract at 500 mg/kg b.w. showed reduced absolute ethanol-induced gastric lesion sizes by > 99% (p < 0.05). This protective effect was comparable to that conferred by OMP. The pH of the gastric mucus decreased in dose-dependent manner from 5.51 to 3.82 and there was a significant increase in NP-SH concentrations.ConclusionsResults from the study, suggest that the mass spectrometry standardized methanolic extract of Gracillaria changii possesses anti-inflammatory, gastroprotective and anti-ulcerogenic properties. Further examination of the active constituent of the extract and its mechanism of action is warranted in the future.

Gastroprotective effects of essential oil from Protium heptaphyllum on experimental gastric ulcer models in rats

Peptic ulcers are a common disorder of the entire gastrointestinal tract, its etiology has not been completely elucidated. The basic physiopathological of peptic ulcers result from an imbalance between some endogenous aggressive factor and cytoprotective factors. The treatment of this disease is usually done with antacids or proton pump, but are currently being used plants derivated compounds. We evaluated the gastroprotective properties and its possible mechanisms of action of the essential oil from Protium heptaphyllum (Aubl.) Marchand, Burseraceae (BB). The formation of ulcers, were evaluated in three experimental models, through the induction of gastric lesions by ethanol, nonsteroidal anti-inflammatory drugs and acetic acid. The mechanisms of action were evaluated through the pylorus ligature experiment, western blot, GSH, GR, SOD, GPx, MDA and MPO activities. BB significantly inhibited the formation of ulcers induced by the three different models, increased the GSH and GR levels and maintained the same levels of SOD and GPx of the sham group, inhibited MPO and MDA, did not produce significant modification in gastric juice content and showed increased COX-2 and EGF. BB exerts its gastroprotective activity, possibly, by increasing COX-2 and EGF expression and due to its possible antioxidant property.

Gastroprotective Effect and Cytotoxicity of Labdeneamides with Amino Acids

Semisynthetic aromatic amides from ARAUCARIA ARAUCANA diterpene acids have been shown to display a relevant gastroprotective effect with low cytotoxicity. The aim of this work was to assess the gastroprotective effect of amino acid amides from imbricatolic acid and its 8(9)-en isomer in the ethanol/HCl-induced gastric lesions model in mice as well as to determine the cytotoxicity of the obtained compounds on the following human cell lines: normal lung fibroblasts (MRC-5), gastric adenocarcinoma (AGS), and liver hepatocellular carcinoma (Hep G2). The diterpenes 15-acetoxyimbricatolic acid, its 8(9)-en isomer, 15-hydroxyimbricatolic acid, and the 8(9)-en derivative, bearing a COOH function at C-19, were used as starting compounds. New amides with C-protected amino acids were prepared. The study reports the effect of a single oral administration of either compound 50 min before the induction of gastric lesions by ethanol/HCl. Some 20 amino acid monoamides were obtained. Dose-response experiments on the glycyl derivatives showed that at a single oral dose of 100 mg/kg, the compounds presented an effect comparable to the reference drug lansoprazole at 20 mg/kg and at 50 mg/kg reduced gastric lesions by about 50%. All derivatives obtained in amounts > 30 mg were compared at a single oral dose of 50 mg/kg. The best gastroprotective effect was observed for the exomethylene derivatives bearing a valine residue at C-19 either with an acetoxy or free hydroxy group at C-15. The tryptophanyl derivative from the acetate belonging to the 8,9-en series presented selective cytotoxicity against hepatocytes. The glycyl amide of 15-acetoxyimbricatolic acid was the most cytotoxic and less selective compound with IC₅₀ values between 47 and 103 µM for the studied cell lines. This is the first report on the obtention of semisynthetic amino acid amides from labdane diterpenes.

Gastric healing effect of methanolic and alkaloidic fraction from Strychnos pseudoquina

Strychnos pseudoquina St. Hill (Loganiaceae) is used in folk medicine to treat malaria, gastric ulcer and gastritis. In the present studies a methanolic extract (ME) and alkaloidic fraction (AF) from S. pseudoquina leaves were investigated for their ability to heal gastric ulcer by the method of TAKAGI et al., (1969) [1]. Male Wistar rats (n=6) were treated orally with saline (vehicle), cimetidine (100mg/Kg), ME (250mg/kg) or AF (250mg/kg) for 14 consecutive days after gastric lesion induction by acetic acid. Vital organs and body weight were also analyzed to evaluate the subacute toxicity. Samples of gastric tissue were collected for histological and immunohistochemical analysis. We also evaluated the in vitro anti-Helicobacter pylori action of AF from S. pseudoquina. Macroscopic analysis after 14-day ME treatment showed no significant healing action in relation to vehicle-treated rats. However, the gastric lesion of animals treated with EAF, at the same dose, induced significant reduction (p&lt;0.05) in internal (42%) and external (38%) lesion area (mm2). The regenerative areas of AF (1611.7±28.14µm) and ME (1516.7±36.45µm) were significantly increased (p&lt;0.01) when compared to animals treated with vehicle (1462.0±25.2µm) or cimetidine (1489.5±17.56µm). Immunochemical staining for PCNA showed that AF treatment stimulates cellular proliferation and increases angiogenesis in the region of gastric mucosa regeneration. We also observed anti-Helicobacter pylori with MIC of 75µg/ml. We concluded that EAF from S. pseudoquina presents expressive gastric healing action by increasing cell proliferation in gastric mucosa, while augmenting angiogenesis and antibacterial action against H. pylori with absence of toxicity for 14 consecutive days.

Gastroprotective effect of hydroalcoholic extract from barks of Persea major Kopp (Lauraceae) in rats

Persea major Kopp (Lauraceae) is used in folk medicine to treat skin wounds and gastric disorders. This study evaluates the potential of crude hydroalcoholic extract (EHA) as gastroprotective and its acute toxicity. Swiss mice were treated with EHA by oral (p.o.) and intraperitoneal (i.p.) routes with doses of 0.125 to 10 g/kg and were observed until 14 days after the administration of the extract. The calculated LD50 of EHA after i.p. administration was 480 mg/kg in mice and the LD50 values of EHA by the oral route were calculated to be up to 10 g/kg in mice. Wistar rats were orally pretreated with EHA (30, 100, 300 and 1000 mg/kg) before induction of gastric lesions by 70% ethanol (0.5 mL/animal, p.o.), indomethacin (20 mg/kg, s.c.) and hypothermic restraint stress (during 3 h at 4 ºC). The EHA protected the gastric mucosa against lesions induced by ethanol, but did not reduce the stress- and indomethacin-induced gastric lesions. When the EHA was injected into the duodenal lumen (i.d.), the volume, pH and total acidity of the gastric secretion of rats with pylorus ligature was not altered with different doses of the extract. Results therefore suggest that the cytoprotective effect of this extract against the direct necrosing action of ethanol and its effect were not related with reduction of gastric acid secretion.

Plantas medicinais usadas nos distúrbios do trato gastrintestinal no povoado Colônia Treze, Lagarto, SE, Brasil

Os modelos de desenvolvimento sócio-econômicos adotados pela sociedade humana refletem diferentes formas de relacionamento com a natureza, as quais no paradigma vigente têm levado à grande perda de recursos naturais. Na esfera dessa relação, a conservação e preservação da biodiversidade da flora medicinal torna-se fundamental, pela importância que as plantas medicinais assumem como potencial genético para o desenvolvimento de novas drogas, e como acesso primário à saúde para muitas comunidades. Utilizando a abordagem etnofarmacológica na pesquisa de plantas medicinais, este trabalho teve por objetivo estudar as plantas medicinais utilizadas popularmente contra distúrbios do trato gastrintestinal no povoado Colônia Treze em Lagarto, SE, comunidade que tem o uso popular das plantas medicinais inserido em sua cultura. Sua metodologia abrangeu trabalho de campo na comunidade, adotando o método etnográfico qualitativo rápido. A amostra foi composta por líderes da comunidade, usuários de plantas e praticantes da medicina popular. Baseando-se nas indicações populares sobre o uso das plantas medicinais, selecionaram-se oito plantas que foram submetidas aos experimentos farmacológicos. As plantas testadas no Modelo de Trânsito Intestinal não produziram alteração na motilidade. Já as submetidas ao Modelo de Indução de Lesão Gástrica aguda, mostraram-se efetivas na atividade antiulcerogênica. A partir destes resultados propõem-se estratégias de desenvolvimento local para esta comunidade, que aliem a conservação da flora medicinal à melhoria de sua qualidade de vida.

IL-18 mediates the formation of stress-induced, histamine-dependent gastric lesions

A role of IL-18 in the induction of gastric lesions by water immersion and restraint stress (WRS) was investigated. When wild-type BALB/c mice were exposed to WRS, levels of IL-18 in the serum and stomach increased rapidly with the development of acute gastric lesions. In IL-18-deficient mice [IL-18 knockout (KO) mice] similarly exposed to WRS, no gastric lesions were observed, but the administration of IL-18 before exposure to WRS resulted in the induction of WRS-induced gastric lesions. WRS enhanced gastric histidine decarboxylase (HDC) activity with concomitant increases in gastric histamine content. In IL-18 KO mice, the WRS-induced elevation of gastric HDC activity and histamine levels was much less than that in wild-type mice, but it was augmented by prior administration of IL-18. Treatment of wild-type mice with cimetidine, a histamine H2 receptor antagonist, inhibited the formation of WRS-induced gastric lesions with no effect on the induction of gastric IL-18 by WRS. Levels of corticosterone, one of the stress indicators, were lower in IL-18 KO mice than in wild-type mice. The glucocorticoid receptor antagonist mifepristone had no effect on gastric IL-18 and histamine levels but aggravated the stress-induced gastric lesions, indicating that corticosterone was not involved in the IL-18-mediated formation of stress-induced gastric lesions. These results indicate that IL-18 is involved in the induction of gastric lesions by WRS through augmentation of HDC activity and production of histamine in the stomach.

Evaluation of the anti-ulcer and toxicity profile of &lt;i&gt;Aloe buettneri&lt;/i&gt; in laboratory animals

The anti-ulcerogenic potential of the leaf methanol extract of Aloe buettneri A. Berger was investigated using three methods of gastric lesion induction in experimental Wistar rats (150-200 g) and mice (20-25 g): 1. HCl/ethanol-induced gastic lesions, 2. Indomethacin-HCl/ethanol-induced gastric lesions, and 3, Pylorus ligation-induced gastric lesions. Mice were used in acute and sub acute toxicity tests. Oral administration of the extract of Aloe buettneri to the rats and mice (500-1000 mg/kg) dose-dependently prevented the formation of acute gastric lesions induced using the three experimental techniques. The dose-dependent reduction of lesion formation was accompanied by a significant increase in gastric mucus production in mice. Inhibition of lesion formation was 22 and 54 % in mice, 25 and 77% in rats for the doses of 500 and 1000 mg/kg when the HCl/ethanol mixture was given. Pre-treatment, by oral route, with indomethacin significantly reduced the ability of the extract to inhibit the formation of HCl/ethanol-induced lesions, inhibition dropping to 11% for the dose of 1000 mg/kg. When the rats were subjected to pylorus ligation, the level of lesion inhibition was 36 and 68% for the two doses of extract. Gastric acid secretion reduced to 88 and 79mEq/l compared with105 mEq/l for the controls. Acute toxicity studies did not reveal toxic effects up to the dose of 10 g/kg. However, sub acute studies revealed toxicity effects in heart (pericarditis), lung (diffuse alveolar disease) and liver (chronic active hepatitis) tissue. These results confirm the ethnomedical use of Aloe buettneri in the management of gastroduodenal ulcer disease and suggest that toxic effects may result from prolonged intake of high doses of the extract. Keywords: Aloe buettneri, antiulcer activity, toxicity profile African Journal of Traditional, Complementary and Alternative Medicines Vol. 3(2) 2006: 8-20

Effect of Moxibustion at Acupoints Ren-12 (Zhongwan), St-25 (Tianshu), and St-36 (Zuzanli) in the Prevention of Gastric Lesions Induced by Indomethacin in Wistar Rats

This study was aimed at assessing the physical characteristics underlying the action of moxibustion at acupoints Ren-12 (Zhongwan), St-25 (Tianshu), and St-36 (Zuzanli) in preventing acute injuries of the gastric mucous membrane induced by indomethacin in Wistar rats. Induction of gastric lesions, by means of intragastric administration of indomethacin (100 mg/kg), in adult male Wistar rats was followed by treatment with moxibustion using Artemisia vulgaris dried leaves at 60 or 45 degrees C, heating with Artemisia vulgaris charcoal at 50 degrees C, heating with a regular tobacco cigar at 50 degrees C, and heating with a regular water pad at 50 degrees C, The effects of the different heating protocols over the gastric lesions were then compared. In addition, another group of animals was pretreated with capsaicin (100 mg/kg, s.c.), in order to lesion C fibers and, 15 days later, subjected to indomethacin administration and moxibustion treatment. Moxibustion was significantly more efficient at 60 degrees C than at 45 degrees C in preventing gastric lesions triggered by indomethacin. Moxibustion applied in acupoints provided a significant reduction of the lesion area, which was two times less than that of animals stimulated in a nonacupoint (sham group). Comparing the therapeutic effects provided by different forms of heating over the gastric lesions, the burning of dry leaves of Artemisia vulgaris was significantly more efficient in preventing gastric lesions than moxibustion made with Artemisia charcoal or tobacco (cigar) or by heating the animal with a water pad. Desensitization of the afferent sensory C fibers by capsaicin significantly diminished the ability of moxibustion to block the lesions in the gastric mucous membrane. Moxibustion can efficiently prevent indomethacin-induced gastric lesions in rats and this effect is dependent on the temperature, the material used for moxibustion, the use of acupuncture points, and the integrity of C fibers.

Role of direct cytotoxic effects of NSAIDs in the induction of gastric lesions

A major clinical problem encountered with the use of non-steroidal anti-inflammatory drugs (NSAIDs), is gastrointestinal complications. We previously reported that NSAIDs induce both necrosis and apoptosis in vitro. We here examined the cyclooxygenase (COX) dependency of this cytotoxic effect of NSAIDs and its involvement in NSAID-induced gastric lesions. Necrosis and apoptosis by NSAIDs was observed with all selective COX-2 inhibitors except rofecoxib and was not inhibited by exogenously added prostaglandin E 2, suggesting that cytotoxicity of NSAIDs seems to be independent of the inhibition of COX. Intravenously administered indomethacin, which completely inhibited COX activity at gastric mucosa, did not produce gastric lesions. Orally administered selective COX-2 inhibitors, which did not inhibit COX at gastric mucosa, also did not produce gastric lesions. Interestingly, a combination of the oral administration of each of all selective COX-2 inhibitors except rofecoxib with the intravenous administration of indomethacin clearly produced gastric lesions. These results suggest that in addition to COX inhibition by NSAIDs, direct cytotoxicity of NSAIDs may be involved in NSAID-induced gastric lesions.

Gastric cytoprotective anti-ulcer effects of the leaf methanol extract of Ocimum suave (Lamiaceae) in rats

The anti-ulcerogenic potential of the leaf methanol extract of Ocimum suave (Lamiaceae) was investigated using four methods of gastric lesion induction in experimental Wistar rats (150–200 g): (1) HCl/ethanol-induced gastric lesions, (2) Absolute ethanol-induced gastric lesions, (3) Indomethacin–HCl/ethanol-induced gastric lesions, (4) Pylorus ligation-induced gastric lesions. Administration of the extract of O. suave to the rats by oral route (75–500 mg/kg) dose-dependently prevented the formation of acute gastric lesions induced using the four experimental techniques. The dose-dependent reduction of lesion formation was in all cases accompanied by significant increases in gastric mucus production. At the dose of 250 mg/kg there was complete inhibition of gastric lesions induced using the HCl/ethanol solution. Pre-treatment, by intraperitoneal route, with indomethacin significantly reduced the ability of the extract to inhibit the formation of HCl/ethanol-induced lesions. When the rats were subjected to pylorus ligation, the dose of 500 mg/kg completely inhibited lesion formation but did not have any effect on gastric acid secretion compared with the controls. The mucus secretion promoting effect of the extract was most significant when the gastric environment was highly acidic. These results suggest that a new anti-ulcer therapy regimen may be formulated which does not require the use of antacids and anti-secretory agents.

Induction of gastric lesions by cyclooxygenase (COX-2) inhibitors in the stomach of adjuvant-induced arthritic rats

Induction of gastric lesions by cyclooxygenase (COX-2) inhibitors in the stomach of adjuvant-induced arthritic rats

Induction of gastric lesions by cyclooxygenase (COX-2) inhibitors in the stomach of adjuvant-induced arthritic rats

Induction of gastric lesions by cyclooxygenase (COX-2) inhibitors in the stomach of adjuvant-induced arthritic rats

Monochloramine impairs mucosal blood flow response and healing of gastric lesions in rats: relation to capsaicin-sensitive sensory neurons.

We examined the effects of monochloramine (NH2Cl) on the gastric mucosal blood flow (GMBF) response and the healing of ethanol-induced gastric lesions in rats. Rats fasted for 18 h were given the 99% ethanol p.o. for induction of gastric lesions, and were fed normally from 1 h later onwards. Monochloramine, at non-ulcerogenic doses (5 to approximately 20 mmol/L), was given p.o. twice daily for 7 days, starting 2 h after ethanol treatment. Gastric lesions caused by ethanol healed almost completely within 7 days with re-epithelialization. The repeated administration of NH2Cl significantly delayed the healing of ethanol-induced gastric lesions in a dose-dependent manner. The damaged mucosa showed a marked rise in H+ permeability, resulting in luminal acid loss, but this process was accompanied by an increase of mucosal blood flow. Monochloramine did not affect the increased mucosal H+ permeability observed in the stomach after damage by ethanol, but significantly inhibited the mucosal hyperemic response associated with luminal acid loss. Prior exposure of the mucosa to NH2Cl (20 mmol/L) did not affect the gastric hyperemic response caused by mucosal application of misoprostol (a prostaglandin E1 derivative) or NOR-3 (a nitric oxide donor), but totally attenuated the increase of GMBF in response to intragastric capsaicin. Impaired healing and GMBF responses were also observed in rats following chemical ablation of capsaicin-sensitive sensory neurons. These results suggest that NH2Cl impaired the healing of acute gastric mucosal lesions at low concentrations, and this action may be attributable, at least partly, to the impairment of gastric hyperemic response caused by the dysfunction of capsaicin-sensitive sensory neurons.