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1.
Planta Med ; 86(1): 32-44, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31689719

RESUMO

Gastric ulcer is a major health problem. Current treatment options of gastric ulcer, including antagonists of histamine H2 receptor and inhibitors of the proton pump, do not cure gastric ulcers, but only provide temporary relief of symptoms and can be associated with severe side effects. The lack of effective and safe medications for this global health problem urges for the discovery of novel classes of compounds with potent activity and an acceptable safety profile. Ethanol-induced ulceration in rats was used to evaluate the gastroprotective activity of casuarinin, an ellagitannin isolated from Melaleuca leucadendra. Casuarinin (25, 50, and 100 mg/kg) reduced the ulcer area by 45, 78, and 99%, respectively, compared with the ulcer group. Casuarinin (100 mg/kg) increased mucin content by 1.8-fold and reduced acidity by 42%. At the same dose, it also increased the levels of reduced glutathione by 194%, catalase by 586%, and prostaglandin E2 to its normal level. In contrast, it attenuated the ethanol-increased levels of malondialdehyde by 56%, TNF-α by 58%, and caspase-3 by 87%. Histological findings demonstrated that casuarinin exhibited a protective effect against tissue alterations in response to the ethanol-induced ulcer. Casuarinin suppressed the immunoexpression of nuclear factor-kappa B, cyclooxygenase-2, and inducible nitric oxide synthase to their normal values. It also induced the expression of heat shock protein-70, reaching up to 4.9-fold in comparison with the ulcer group. The potent gastroprotective effect of casuarinin was thus attributed to its anti-inflammatory, antioxidant, and antiapoptotic effects. Our results suggest the potential application of casuarinin as an antiulcer agent from natural sources.


Assuntos
Antiulcerosos/isolamento & purificação , Taninos Hidrolisáveis/uso terapêutico , Melaleuca/química , Extratos Vegetais/uso terapêutico , Úlcera Gástrica/prevenção & controle , Animais , Antiulcerosos/farmacologia , Ciclo-Oxigenase 2/metabolismo , Etanol , Proteínas de Choque Térmico HSP70/metabolismo , Taninos Hidrolisáveis/química , Taninos Hidrolisáveis/isolamento & purificação , Masculino , Estrutura Molecular , Mucinas/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia
2.
Eur J Pharm Sci ; 140: 105101, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31639436

RESUMO

Gastric irritation and ulcerogenic effect of the acidic NSAIDs are of the most challenging problems in designing novel anti-inflammatory agents. In this study, the new prodrugs were prepared through Steglich esterification reaction between the carboxylic acid functional group of etodolac or tolfenamic acid and thymol. The structures were confirmed by IR, 1H NMR, 13C NMR, mass spectroscopy and elemental analysis. Their chemical stability in addition to a kinetic study of their hydrolysis in 20% liver homogenate and 10% buffered plasma were investigated. In vitro enzymatic hydrolysis showed half-life times 88.84 and 106.61 min for the prodrugs of etodolac and tolfenamic acid, respectively. Their ability to inhibit paw edema and their ulcerogenic potential were assessed in rats and compared to their parent drugs. the prodrugs were found to be stable in different pHs at room and body temperatures. Both prodrugs proved to possess high percentage of inhibition of paw edema (94.68 & 97.1%) in rats comparable to that of the parent drugs (90.33 & 93.23%) and, most importantly with lower ulcerogenic potential. The prodrugs are expected to be converted to their parent drugs rapidly in plasma and liver in vivo and proved to be safer than their parent drugs. The study opens a perspective chance that can be a backbone for further investigations.


Assuntos
Anti-Inflamatórios/síntese química , Edema/tratamento farmacológico , Etodolac/síntese química , Pró-Fármacos/síntese química , Úlcera Gástrica/induzido quimicamente , ortoaminobenzoatos/síntese química , Animais , Anti-Inflamatórios/farmacologia , Desenho de Drogas , Estabilidade de Medicamentos , Etodolac/farmacologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Hidrólise , Cinética , Fígado/metabolismo , Masculino , Estrutura Molecular , Plasma/metabolismo , Pró-Fármacos/farmacologia , Ratos , Ratos Wistar , Úlcera Gástrica/prevenção & controle , Relação Estrutura-Atividade , Temperatura Ambiente , ortoaminobenzoatos/farmacologia
3.
Food Chem Toxicol ; 132: 110739, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31374297

RESUMO

The aim of the study was to investigate the effects of four Aronia melanocarpa-based juices in a rat model of indomethacin-induced gastric ulceration. THE JUICES WERE: AM1 and AM2 (produced from aronia fruits at 20 °C and 60 °C, respectively), AMRC (a mixture of AM2 with Rosa canina extract) and AMAV (aronia juice with Alchemilla vulgaris). Male Wistar rats were used. Each of the juices (10 ml/kg) was administered for 10 days. Indomethacin (30 mg/kg) was injected subcutaneously and after 4 h, the effects were estimated. Indomethacin caused heavy destructions of the gastric mucosa, increased the expression of Bax and decreased the expression of Bcl-2, induced a certain increase in lipid peroxidation and a slight decrease in gastric PGE2 content. The pretreatment with the juices reduced the severity of indomethacin-induced gastric lesions and antagonized the effects of indomethacin on apoptosis and lipid peroxidation. The highest was the protective effect of AMAV, the juice with the highest polyphenolic content. The protective effect of Aronia melanocarpa-based juices against indomethacin-induced gastric lesions could be attributed to their polyphenolic contents. The mechanism involved to the highest extent in the protective effect of the juices was the inhibition of apoptosis.


Assuntos
Alchemilla/química , Anti-Inflamatórios não Esteroides/toxicidade , Sucos de Frutas e Vegetais , Indometacina/toxicidade , Extratos Vegetais/farmacologia , Rosa/química , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Animais , Dinoprostona/metabolismo , Modelos Animais de Doenças , Masculino , Fenóis/análise , Photinia , Compostos Fitoquímicos/análise , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
4.
Acta Biochim Biophys Sin (Shanghai) ; 51(9): 925-933, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31435637

RESUMO

In study, we aimed to determine the mechanisms underlying the gastroprotective effects of sodium copper chlorophyllin (SCC) against ethanol-induced gastric ulcer injury in mice. First, the gastroprotective effects of SCC against gastric ulcer induced by ethanol were assessed. Then, biochemical, histopathological, immunohistochemistry assays, and western blot analysis were conducted to determine the possible mechanisms of action underlying the effects of SCC. Compared to the effects of omeprazole (OME) in a confirmed mouse model of ethanol-induced gastric ulcer injury, treatment with various doses of SCC resulted in up-regulation of Bcl-2 and down-regulation of the pro-apoptotic protein Bax. Significant decreases in the levels of the malondialdehyde (MDA), myeloperoxidase (MPO), and NO in the gastric tissues were observed. Furthermore, inflammatory cytokine analysis revealed that SCC treatment inhibited the expressions of TNF-α and IL-6, greatly reduced the phosphorylation level of IκB, and repressed the nuclear translocation of NF-κB p65, which demonstrated that SCC inhibited the activation of the NF-κB pathway. The present findings suggest that the protective effects of SCC may be beneficial as a potential preventive and therapeutic agent for gastric ulcer through the NF-κB pathway. Taken together, SCC administration significantly decreased the levels of MPO, NO, and MDA in gastric tissue and exerted a powerful anti-inflammatory activity as demonstrated by reduction in the secretions of proinflammatory mediators such as IL-6 and TNF-α in the serum of mice exposed to ethanol.


Assuntos
Clorofilídios/uso terapêutico , Etanol/efeitos adversos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Animais , Feminino , Interleucina-6/metabolismo , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Peroxidase/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/metabolismo
5.
Pharm Biol ; 57(1): 543-549, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31429615

RESUMO

Context: HemoHIM is a medicinal herbal preparation of Angelica gigas Nakai (Apiaceae), Cnidium officinale Makino (Umbelliferae), and Paeonia japonica Miyabe (Paeoniaceae) developed for immune regulation. HemoHIM has been investigated for its ability to enhance tissue self-renewal and stimulate immune systems. To date, studies on the protective effects of HemoHIM against gastritis and gastric ulcers have not been conducted. Objective: The protective effects of HemoHIM using models of indomethacin and ethanol/hydrochloric acid (EtOH/HCl)-induced gastric mucosal injury were investigated. Materials and methods: Rats were divided into five groups (n = 10): control, indomethacin, or EtOH/HCl groups, HemoHIM 250, 500 mg kg-1, and cimetidine 100 mg kg-1, respectively. Indomethacin (80 mg kg-1) and 60% EtOH/150 mM HCl were administered orally 1 h after the administration of samples and rats were anesthetized 3 h after induction. The lesion area (%), inhibition ratio (%), and total acidity were investigated, and tissues were histopathologically analyzed using hematoxylin and-eosin (H&E) staining. Results: HemoHIM significantly reduced gastric injury in indomethacin-induced model (250 and 500 mg kg-1; 64.30% and 67.75%, p < 0.001) compared to indomethacin group. In the EtOH/HCl-induced model, HemoHIM reduced gastric lesion (250 and 500 mg kg-1; 61.05% and 73.37%, p < 0.001) and gastric acidity (250 and 500 mg kg-1; 37.80 and 45.20 meq L-1, p < 0.001) compared to EtOH/HCl group. H&E staining of the gastric mucosa showed decreased erosion and hemorrhage in HemoHIM group compared to EtOH/HCl group. Discussion and conclusions: Based on the results, HemoHIM is potential candidate for the treatment of gastritis and gastric ulcers.


Assuntos
Extratos Vegetais/uso terapêutico , Úlcera Gástrica/prevenção & controle , Animais , Antiulcerosos , Etanol , Mucosa Gástrica , Ácido Clorídrico , Indometacina , Masculino , Fitoterapia , Ratos Sprague-Dawley , Úlcera Gástrica/induzido quimicamente
6.
Free Radic Res ; 53(6): 596-610, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31215272

RESUMO

The cytoprotective action of the synthetic resveratrol (Resv) congener, E-3,3',5,5'-tetrahydroxystilbene (designated as HST-1) against indomethacin (IND)-induced stomach ulceration has been established using a mice model. HST-1 reversed the adverse effects of IND on several inflammatory (myeloperoxidase, cytokines, adhesion molecules etc.) and ulcer-healing (cyclooxygenases, prostaglandin, growth factors and their receptors etc.) parameters in mice. More importantly, HST-1 down-regulated TNF-α and the TNF-α-mediated activation of NF-κB and JNK/MAPK pathways that are the key determinants in the IND-gastropathy. The effect of HST-1 on all these factors was significantly better than that of Resv, misoprostol, and omeprazole. HST-1 also did not induce small intestinal mucosal injury, unlike some of the proton pump inhibitors. On the other hand, Resv reduced activation of the prosurvival ERK1/2 pathway that may explain its contraindicative property in the gastrointestinal tract.


Assuntos
Antiulcerosos/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Resveratrol/farmacologia , Úlcera Gástrica/prevenção & controle , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Administração Oral , Animais , Antiulcerosos/administração & dosagem , Indometacina , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , NF-kappa B/metabolismo , Resveratrol/administração & dosagem , Úlcera Gástrica/induzido quimicamente , Fator de Necrose Tumoral alfa/metabolismo
7.
Food Funct ; 10(7): 3965-3976, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31204764

RESUMO

The dry root of Hedysarum polybotrys Hand.-Mazz., commonly known as "Hong Qi", has a variety of health benefits. The present study was undertaken to explore the anti-gastric ulcer potential effect of Hedysarum polysaccharides (HPS; HPS-50, HPS-80), the principal active fraction of Radix Hedysari (RH). The anti-gastric ulcer effects of HPS were evaluated using an animal model of ulcerative lesions induced by acetic acid. The effects of antioxidant factors, anti-inflammatory cytokines, and mucosal blood flow regulatory factor levels in the gastric tissue homogenate of rats were analyzed for the bioactivities of HPS. The results showed that, compared with the acetic acid-induced ulcerated group, the ulcer inhibition rate of HPS-treated rats was significantly increased. The pathological findings suggested that mucosal regeneration, cell migration, and inflammatory cell infiltration were decreased, and collagen fibers were significantly reduced. Extensive granulation tissue proliferation indicated the healing stage was initiated, suggesting a good prognosis. The oxidative stress status of the gastric ulcer rats was improved, the levels of TNF-α and IL-6 were significantly decreased, and the levels of PGE-2 and NO were increased (P < 0.05). HPS-80-H may be a promising ingredient for incorporation into functional foods or nutritional supplements for the prevention of gastric ulcers.


Assuntos
Ácido Acético/efeitos adversos , Antiulcerosos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Polissacarídeos/farmacologia , Ranunculaceae/química , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , China , Citocinas/metabolismo , Dinoprostona/metabolismo , Modelos Animais de Doenças , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Interleucina-6/metabolismo , Masculino , Membrana Mucosa/efeitos dos fármacos , Estresse Oxidativo , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Estômago/efeitos dos fármacos , Estômago/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Fator de Necrose Tumoral alfa/metabolismo , Cicatrização/efeitos dos fármacos
8.
Artigo em Russo | MEDLINE | ID: mdl-31095130

RESUMO

BACKGROUND: The relevance of this study is determined by the need for the scientifically sound substantiation of the possibility for the use of acidic mineral waters in the treatment of digestive diseases taking into consideration their widespread application in ethnomedicine, in particular in the Republic of Tuva. AIM: The objective of the present study was to elucidate the gastroprotective action of acidic mineral water from the Azhyg-Sug source (Republic of Tyva) on the experimental animals as exemplified by the model of ulcerogenesis under the conditions of immobilization stress. MATERIAL AND METHODS: The experimental studies were carried out with the use of 32 white rats of the Wistar line. Ulcerogenesis was initiated by means of immobilization stress. We evaluated the pathomorphological characteristics of the gastric mucosa and the number of destructions based on the Pauls index. The state of the lipid peroxidation system and antioxidative protection were determined from the content of malon dialdehyde and reduced glutathione, extracellular catalase and superoxide dismutase activities in erythrocytes. RESULTS: The study has demonstrated that the mineral water from the Azhyg-Sug source slows down the development of the inflammatory and destructive necrotic processes in the mucosa of the stomach of albino rats. The depth of erosion in the animals receiving mineral water was 2.3 and 3.4 times lower than in the control animals (p≤0.05). The antioxidant effect of mineral water was confirmed by the 14-20% decrease of the MDA concentration as well as by the increase of the catalase and superoxide dismutase (SOD) activities by 21-25% and 20-30% respectively in comparison with the control animals. CONCLUSION: The Azhyg-Sug mineral water has the strong gastroprotective influence on the experimental animals having the induced neurogenic ulcer. One of the mechanisms underlying the gastroprotective action of the investigated mineral water arises from its ability to inhibit the processes of lipid peroxidation with the simultaneous enhancement of the activity of the antioxidant system of the organism.


Assuntos
Antioxidantes/uso terapêutico , Águas Minerais/uso terapêutico , Úlcera Gástrica/prevenção & controle , Animais , Modelos Animais de Doenças , Substâncias Protetoras , Ratos , Ratos Wistar
9.
Biomed Res Int ; 2019: 9514703, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949513

RESUMO

Gastric ulcers are a common problem in upper gastrointestinal tract (GI) disorders. Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most aggressive factors leading to inducing gastric ulcers. Natural products with lower toxicity and safety are currently sought as a potential source to minimize the effect of the gastric ulcers. Perilla frutescens or Nga-mon (in Thai) leaves are rich in rosmarinic acid (RA), which has antioxidant, anti-inflammatory, and anticancer effects. This study investigates the protective effect of ethanolic extract (EE) and aqueous fraction (AF) from Perilla frutescens leaves, which are rich in RA, on indomethacin- (IND-) induced gastric ulcer in a rat model. The EE at the doses of 50 and 500 mg/kg body weight, AF at the doses of 50, 250, and 500 mg/kg body weight, or famotidine (a standard drug) were administered for 14 days prior to ulcer induction. The ulceration was performed by intragastric administration of IND. Gross gastric ulcers and biological and histological parameters were examined. The pretreatment with AF had more significant effects than EE, including reduced ulcer index, decreased gastric secretion volume and decreased acidity, but it had an elevated gastric pH relative to the IND-induced gastric ulcer. In a histopathological study, the EE and AF decreased mucosal ulcer, inflammatory infiltration, and degenerative lining cells. The IND-induced expression of inflammatory mediators was significantly attenuated with EE and AF. The experiment also remarkably showed the preservation of mucus and apoptosis protection of EE and AF on a gastric mucosal ulcer. The findings demonstrated that the EE and AF of perilla leaves were capable of protecting the stomach against gastric ulcers induced by IND through anti-inflammatory and antiapoptotic mechanisms that should be further investigated. It is suggested that Perilla frutescens leaf could be a potential alternative source of RA as a therapeutic agent and food supplement for NSAID-induced gastric injuries.


Assuntos
Cinamatos , Depsídeos , Indometacina/efeitos adversos , Perilla frutescens/química , Folhas de Planta/química , Úlcera Gástrica , Animais , Cinamatos/química , Cinamatos/farmacologia , Depsídeos/química , Depsídeos/farmacologia , Relação Dose-Resposta a Droga , Indometacina/farmacologia , Masculino , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Úlcera Gástrica/prevenção & controle
10.
Medicina (Kaunas) ; 55(3)2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-30862060

RESUMO

Background and objectives: Zingerone is an ingredient of ginger (Zingiber officinale) with different pharmacological activities. Several studies have investigated the effect of zingerone on various gastrointestinal diseases, including irritable bowel syndrome and diarrhea. This study is aimed to evaluate the effect of zingerone on ethanol-induced gastric ulcers in rats. Materials and Methods: Gastric ulcers were induced by ethanol (96%, 5 mL/kg, po) in male wistar rats and zingerone (50, 100, and 200 mg/kg) was administrated orally. Normal saline and ranitidine were used as negative and positive control, respectively. In this study, the number and length of ulcers, and malondialdehyde (MDA) and nitric oxide (NO) levels in stomach tissues were determined. Results: The findings showed that the mean number and length of gastric ulcers were significantly lower in zingerone-received groups than ethanol group (P < 0.05). The level of malondialdehyde was decreased in the stomach of zingerone groups (P < 0.05) compared to the ethanol group. In addition, zingerone treatment prevented the decrease of nitric oxide level by ethanol in the stomach tissue. Conclusions: The present study showed that zingerone has a protective effect on the ethanol-induced gastric ulcer, which may be due to its free radical scavenging activity.


Assuntos
Antiulcerosos/uso terapêutico , Gengibre/química , Guaiacol/análogos & derivados , Fitoterapia , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/farmacologia , Modelos Animais de Doenças , Etanol/administração & dosagem , Etanol/efeitos adversos , Etanol/farmacologia , Mucosa Gástrica/metabolismo , Guaiacol/administração & dosagem , Guaiacol/farmacologia , Guaiacol/uso terapêutico , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/análise , Malondialdeído/metabolismo , Necrose , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Solventes/administração & dosagem , Solventes/efeitos adversos , Solventes/farmacologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle
11.
Life Sci ; 224: 88-94, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30914317

RESUMO

AIMS: Several natural products have been evaluated for management of gastric ulcer induced by non-steroidal anti-inflammatory drugs. Safranal, a plant-derived chemical, has a potent antioxidant and anti-inflammatory properties. The present study was aimed to evaluate possible gastro-protective effects of safranal against indomethacin-induced gastric ulcer in rats. Lansoprazole (a proton pump inhibitor) was used as a reference drug. MATERIALS AND METHODS: Thirty rats were divided into five groups. Groups 1 and 2 received vehicle. Groups 3, 4 and 5 treated with 0.063, 0.25 and 1 mg/kg safranal. Group 6 received 30 mg/kg lansoprazole. All groups except of group 1 received indomethacin (50 mg/kg) ingestion. Six hours later, animals were euthanized and their stomachs were removed. Gastric contents volume and pH were measured. Gastric ulcer area and protective index were evaluated using image J software. Histological changes were evaluated by light microscope. Malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, total antioxidant capacity (TAC) content, tumor necrosis factor-alpha (TNF-α) and Caspase-3 levels were determined in the gastric tissue. KEY FINDINGS: Safranal and lansoprazole normalized gastric volume and pH, reduced gastric ulcer area and produced gastric protection. Indomethacin-induced histological changes and tissue biochemical alterations were ameliorated by the above-mentioned treatments. SIGNIFICANCE: The results of the present study suggest the involvement of anti-secretory, anti-oxidant, anti-inflammatory and anti-apoptotic mechanisms in gastro-protective effect of safranal. In addition, gastro-protective effect of safranal was comparable to lansoprazole.


Assuntos
Antiulcerosos/farmacologia , Cicloexenos/farmacologia , Indometacina/toxicidade , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Úlcera Gástrica/prevenção & controle , Terpenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/toxicidade , Crocus/química , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia
12.
Molecules ; 24(3)2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30754621

RESUMO

Peptic ulcers are currently treated with various drugs, all having serious side effects. The aim of this study was to evaluate the gastroprotective activity of calein D (from Calea urticifolia), a sesquiterpene lactone with a germacrane skeleton. Gastric lesions were induced in mice by administering ethanol (0.2 mL) after oral treatment with calein D at 3, 10 and 30 mg/kg, resulting in 13.15 ± 3.44%, 77.65 ± 7.38% and 95.76 ± 2.18% gastroprotection, respectively, to be compared with that of the control group. The effect found for 30 mg/kg of calein D was not reversed by pretreatment with NG-nitro-l-arginine methyl ester (l-NAME, 70 mg/kg, ip), indomethacin (10 mg/kg, sc) or N-ethylmaleimide (NEM, 10 mg/kg, sc). Hence, the mechanism of action of calein D does not involve NO, prostaglandins or sulfhydryl compounds. Calein D was more potent than carbenoxolone, the reference drug. The findings for the latter are in agreement with previous reports.


Assuntos
Asteraceae/química , Etanol/efeitos adversos , Lactonas/administração & dosagem , Sesquiterpenos de Germacrano/administração & dosagem , Úlcera Gástrica/prevenção & controle , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Etilmaleimida/administração & dosagem , Etilmaleimida/farmacologia , Indometacina/administração & dosagem , Indometacina/farmacologia , Lactonas/química , Lactonas/farmacologia , Camundongos , Estrutura Molecular , NG-Nitroarginina Metil Éster/administração & dosagem , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Prostaglandinas/metabolismo , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/farmacologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Compostos de Sulfidrila/metabolismo
13.
J Basic Clin Physiol Pharmacol ; 30(2): 195-203, 2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30730837

RESUMO

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.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Fluvoxamina/farmacologia , Proteínas de Choque Térmico HSP70/metabolismo , Úlcera Gástrica/prevenção & controle , Animais , Antiulcerosos/farmacologia , Modelos Animais de Doenças , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/prevenção & controle , Proteínas de Choque Térmico HSP70/genética , Indometacina/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos ICR , Restrição Física , Inibidores de Captação de Serotonina/farmacologia , Úlcera Gástrica/induzido quimicamente , Estresse Psicológico/complicações
14.
Pak J Pharm Sci ; 32(1): 7-13, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30772784

RESUMO

Present study was planned to estimate the gastroprotective activity of Euphorbia prostrata plant against aspirin induced gastric ulcers in male adult albino rabbits. The ulcer was induced by oral administration of aspirin in all groups except normal control group. Gastric contents were used to estimate total acid output, gastric volume and gastric pH. Results showed that there was a significant decrease in gastric volume, total acid output, ulcer score and ulcer index in groups treated with extract of E. prostrata and it enhanced the pH of gastric mucosa. Blood samples were collected and serum was used for the estimation of total oxidant status (TOS), total antioxidant capacity (TAC), malondialdehyde (MDA) and catalase (CAT). Results suggested that E. prostrata extract significantly (P<0.05) enhanced the TAC and CAT activity comparable to synthetic antiulcer drug cimetidine while it caused a significant (P<0.05) reduction in TOS and MDA levels. Results of this study revealed that extract of E. prostrata at 10, 20 and 40mg/kg showed gastric protection of 33.79%, 53.15% and 70.66% respectively. Cimetidine was used as a synthetic antiulcer drug in the study, which showed 72.85% gastric protection. From the above mentioned results it was demonstrated that E. prostrata extract at dose rate of 40 mg/kg showed gastroprotective activity similar as cimetidine.


Assuntos
Antiulcerosos/farmacologia , Antioxidantes/farmacologia , Aspirina , Euphorbia , Mucosa Gástrica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Úlcera Gástrica/prevenção & controle , Animais , Antiulcerosos/isolamento & purificação , Antioxidantes/isolamento & purificação , Cimetidina/farmacologia , Citoproteção , Modelos Animais de Doenças , Euphorbia/química , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Malondialdeído/metabolismo , Extratos Vegetais/isolamento & purificação , Coelhos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia
15.
Biomed Pharmacother ; 112: 108582, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30780106

RESUMO

OBJECTIVE: Avicennia schaueriana Stapf is an endemic mangrove species widely used by traditional Brazilian communities as a folk remedy for the treatment of rheumatism, ulcers, and skin wounds. The aim of the present study was to evaluate the gastroprotective potential of the ethyl acetate extract from the leaves of A. schaueriana (As-AcOEt). METHODS: Ultra-performance liquid chromatography coupled with diode-array detection and quadrupole time-of-flight mass spectrometry (UPLC-DAD-QTOF-MS/MS) was performed to identify chemical constituents of the ethyl acetate extract from the leaves ofA. schaueriana. Total phenols, flavonoids and tannins were determined and antioxidant activity was evaluated using the DPPH and ABTS methods. The acute toxicity of As-AcOEt and gastroprotective activity on HCl/ethanol-induced gastric ulcers were assessed and mechanisms of action involving the role of nitric oxide, sulfhydryl compounds, and prostaglandins were investigated. RESULTS: Terpenes, flavonoids and tannins were detected in the extract. As-AcOEt exhibited antioxidant activity, with an EC50 of 42.2 ± 4.4 µg/mL (DPPH) and 73.2% inhibition of ABTS radicals. UPLC-DAD-QTOF-MS/MS analysis identified gallic acid, gallic acid derivative, ellagic acid, myricetin pentoside, myricetin deoxyhexose, quercetin pentoside, quercetin deoxyhexose, and other compounds. Gallic acid was isolated in this species for the first time. During the acute toxicity test, no deaths or changes occurred in the variables evaluated. In the ethanol-induced ulcer model, As-AcOEt reduced the ulcerative lesion index, with 50, 100 and 200 mg/kg achieving 83.8, 88.5 and 86.9% inhibition, respectively. MPO levels decreased and the gastric mucosa of the animals treated with the extract was preserved. Pre-treatment with N-omega-nitro-l-arginine methyl ester (L-NAME; NO blocker) or carbenoxolone (CBXN; NP-SH blocker) reversed the gastroprotective effect of As-AcOEt, but this effect was not reversed with the previous administration of indomethacin. CONCLUSION: The present findings reveal that the extract from the leaves ofA. schaueriana has gastroprotective effects, suggesting the involvement of nitric oxide and nonprotein sulfhydryl compounds, but not prostaglandin. Therefore, the use of A. schaueriana in Brazilian folk medicine for the treatment of gastric disorders has a scientific basis.


Assuntos
Acetatos/uso terapêutico , Antiulcerosos/uso terapêutico , Avicennia , Mucosa Gástrica/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Úlcera Gástrica/prevenção & controle , Acetatos/farmacologia , Animais , Antiulcerosos/isolamento & purificação , Antiulcerosos/farmacologia , Etanol/toxicidade , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Fármacos Gastrointestinais/isolamento & purificação , Fármacos Gastrointestinais/farmacologia , Fármacos Gastrointestinais/uso terapêutico , Masculino , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia
16.
Nutrients ; 11(1)2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30669695

RESUMO

This study aimed to evaluate the effect of Lactobacillus reuteri DSM 17938 (DSM) on ethanol-induced gastric injury, and if its possible mechanism of action is related to inhibiting the transient receptor potential vanilloid type 1 (TRPV1). We evaluated the effect of supplementing 108 CFU•g body wt-1•day-1 of DSM on ethanol-induced gastric injury. DSM significantly reduced the ulcer area (1.940 ± 1.121 mm²) with 3 days of pretreatment. The effects of DSM supplementation were reversed by Resiniferatoxin (RTX), TRPV1 agonist (3 nmol/kg p.o.). Substance P (SP) (1 µmol/L per 20 g) plus 50% ethanol resulted in hemorrhagic lesions, and DSM supplementation did not reverse the lesion area induced by administering SP. TRPV1 staining intensity was lower, SP, malondialdehyde (MDA) and nitrite levels were reduced, and restored normal levels of antioxidant parameters (glutathione and superoxide dismutase) in the gastric mucosa in mice treated with DSM. In conclusion, DSM exhibited gastroprotective activity through decreased expression of TRPV1 receptor and decreasing SP levels, with a consequent reduction of oxidative stress.


Assuntos
Etanol/efeitos adversos , Mucosa Gástrica/patologia , Lactobacillus reuteri/crescimento & desenvolvimento , Probióticos/uso terapêutico , Úlcera Gástrica/prevenção & controle , Substância P/antagonistas & inibidores , Canais de Cátion TRPV/antagonistas & inibidores , Animais , Antioxidantes/metabolismo , Diterpenos/farmacologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Gastrite/induzido quimicamente , Gastrite/metabolismo , Gastrite/prevenção & controle , Glutationa/metabolismo , Lactobacillus reuteri/classificação , Malondialdeído/metabolismo , Camundongos , Substâncias Protetoras/uso terapêutico , Especificidade da Espécie , Estômago/microbiologia , Estômago/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Superóxido Dismutase/metabolismo , Canais de Cátion TRPV/farmacologia
17.
Phytomedicine ; 53: 37-42, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30668410

RESUMO

BACKGROUND: In an increasing search for natural products that may heal the ulcers and avoid its recurrence, limonene appears as a promising candidate. HYPOTHESIS/PURPOSE: The present study aimed to investigate the protective effect of limonene in ethanol-induced gastric ulcers, in addition, to investigate the involvement of antioxidant and anti-inflammatory activities, besides the modulation of gene expression. STUDY DESIGN: Male Wistar rats were orally treated with vehicle (8% tween 80), carbenoxolone (100 mg/kg) or limonene (25, 50 or 100 mg/kg) and then orally received ethanol to induce gastric ulcers formation. METHODS: The activity of myeloperoxidase (MPO) was measured. Levels of glutathione (GSH) and activities of glutathione peroxidase (GPx), glutathione reductase (GR) and superoxide dismutase (SOD) were measured. We investigated the anti-inflammatory effect of limonene measuring the levels of pro-inflammatory cytokines tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and anti-inflammatory cytokine interleukin-10 (IL-10) by ELISA. Additionally, we investigate through real-time PCR (qPCR) the gene expression of nuclear factor-kappa B (Nf-κb), Gpx, Il-1ß, Mpo, and Il-10. RESULTS: Our results showed that limonene 50 mg/kg was the lowest effective dose, offering 93% of reduction in gastric ulcer area compared with the vehicle. There was an increase in mucus production and higher preservation of gastric mucosa integrity after treatment with limonene.There was a reduction in the MPO activity, a biomarker of neutrophils infiltration, and an increase in GPx activity, suggesting an antioxidant effect. Limonene displayed anti-inflammatory activity through decreasing the levels of TNF-a, IL-6, and IL-1ß and increasing the level of IL-10. Limonene could down-regulate the expression of Nf-κb, Il-1ß, and Mpo and up-regulate the expression of Gpx. CONCLUSION: Our results demonstrate that oral treatment with limonene exerts gastroprotection through local mucosal defense mechanisms, such as increasing the mucus production, modulation of the oxidative stress and inflammatory response and inhibition of Nf-κb expression.


Assuntos
Limoneno/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Úlcera Gástrica/prevenção & controle , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Etanol/efeitos adversos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Gastrite/induzido quimicamente , Gastrite/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Limoneno/administração & dosagem , Masculino , Peroxidase/metabolismo , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/genética , Superóxido Dismutase/metabolismo
18.
Equine Vet J ; 51(1): 11-19, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29665126

RESUMO

BACKGROUND: Guidelines regarding the impact and value of prophylaxis or maintenance therapy in equine gastric ulcer syndrome (EGUS) are not well-established or defined. The merits and the magnitude of effects of prophylaxis for spontaneous or recurrent squamous gastric ulceration in horses in training are uncertain. OBJECTIVES: To pool data from randomised controlled trials (RCTs) to eliminate reporting bias and evaluate the efficacy of prophylactic omeprazole in the prevention of EGUS in training horses, and secondarily to compare prophylactic dosages of omeprazole. STUDY DESIGN: Meta-analysis. METHODS: This meta-analysis was conducted according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic literature search identified RCTs comparing omeprazole prophylaxis with sham in prevention of EGUS. Data were analysed using the Mantel-Haenszel test method to calculate risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CIs). Primary outcome was efficacy of prophylaxis. Secondary outcome was endoscopic severity of ulceration. The influence of study characteristics on the outcomes was examined by subgroup analyses. RESULTS: In preventing gastric ulcer occurrence, omeprazole prophylaxis was superior to sham in training horses (7 trials, 566 horses, RR 0.28, 95% CI 0.18-0.43; 23.4% in omeprazole prophylaxis vs. 77.2% in sham; high quality evidence). Prevalence of ulceration was 75.3 and 87.2% in the sham arms of the 1 mg/kg and 2 mg/kg omeprazole groups, respectively. Severity scores were significantly lower for omeprazole vs. sham (mean difference [MD] -1.05; 95% CI -1.35 to -0.69). Subgroup analyses comparing prophylactic omeprazole dosages resulted in a mean difference of -0.94 and -1.60 for the 1 and 2 mg/kg groups, respectively. MAIN LIMITATIONS: Studies showed heterogeneity with regard to prophylactic dose. CONCLUSIONS: Omeprazole prophylaxis in active training horses significantly reduces gastric ulceration compared with no prophylaxis (sham) with the absolute effect of 566 fewer ulcers per 1000 horses treated.


Assuntos
Antiulcerosos/uso terapêutico , Doenças dos Cavalos/prevenção & controle , Omeprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Úlcera Gástrica/veterinária , Animais , Viés , Intervalos de Confiança , Feminino , Doenças dos Cavalos/epidemiologia , Cavalos , Masculino , Razão de Chances , Condicionamento Físico Animal , Prevalência , Fatores de Risco , Úlcera Gástrica/epidemiologia , Úlcera Gástrica/prevenção & controle , Síndrome
19.
Minerva Chir ; 74(2): 126-136, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30019880

RESUMO

INTRODUCTION: One anastomosis gastric bypass (OAGB) is now a recognized mainstream bariatric procedure being adopted by an increasing number of surgeons. The purpose of this review was to present an evidence-based summary of its key technical aspects and prevention and management of its specific complications. EVIDENCE ACQUISITION: We examined PubMed for all published articles on OAGB, including the ones published under one of its various other names. EVIDENCE SYNTHESIS: An ideal OAGB procedure has a long, narrow pouch constructed carefully to avoid going too close to the greater curvature of the stomach especially at the bottom of the pouch and maintains a safe distance from the angle of His. A bilio-pancreatic limb length of 150 cm appears to be safest and a limb length of >200 cm is associated with a significantly increased incidence of protein-calorie malnutrition. We recommend routine closure of Petersen's space to prevent Petersen's hernia and suggest a protocol for micronutrient supplementation. This review also presents evidence-based algorithms for prevention and management of marginal ulcers, protein-calorie malnutrition, and gastroesophageal reflux disease after OAGB. We suggest lifelong supplementation with two multivitamin/mineral supplements (each containing at least 1.0 mg copper and 15 mg zinc) daily, 1.5 mg vitamin B12 orally daily or 3-monthly injection with 1 mg vitamin B12, 120 mg elemental iron daily, 1500 mg elemental calcium daily, and 3000 international units of vitamin D daily. CONCLUSIONS: This review examines key technical steps of OAGB. We also discuss how to prevent and manage its specific complications.


Assuntos
Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Complicações Pós-Operatórias/terapia , Algoritmos , Anastomose Cirúrgica/métodos , Fístula Anastomótica/prevenção & controle , Fístula Anastomótica/terapia , Suplementos Nutricionais , Combinação de Medicamentos , Dilatação Gástrica/prevenção & controle , Dilatação Gástrica/terapia , Refluxo Gastroesofágico/prevenção & controle , Refluxo Gastroesofágico/terapia , Humanos , Micronutrientes/deficiência , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/prevenção & controle , Desnutrição Proteico-Calórica/prevenção & controle , Desnutrição Proteico-Calórica/terapia , Úlcera Gástrica/prevenção & controle , Úlcera Gástrica/terapia , Vitaminas/administração & dosagem
20.
Int J Biol Macromol ; 122: 127-136, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30340003

RESUMO

In order to optimize drug action, new drug formulations have been developed based upon the prodrug approach. This study was inspired by the increasing interest in the field of macromolecular prodrugs and Piroxicam maleate was used as a model drug. A total of five prodrugs were synthesized using beta cyclodextrin, chitosan, pectin, egg albumin, bovine serum albumin. The synthesized conjugates were characterized on the basis of UV, IR and NMR techniques. In-vitro hydrolysis studies were carried out at pH 1.2, pH 7.4, pH 9.0 and in 80% human plasma followed by in-vivo evaluation of analgesic, anti-inflammatory and anti-ulcerogenic potential. The extent of hydrolysis was found to be proportional to increase in pH. Beta cyclodextrin conjugate was found to possess significant analgesic activity whereas chitosan conjugate was found to be the best anti-inflammatory. Pectin conjugate provided maximum protection against ulcers.


Assuntos
Albuminas/química , Quitosana/química , Pectinas/química , Piroxicam/química , Piroxicam/farmacologia , Estômago/efeitos dos fármacos , beta-Ciclodextrinas/química , Animais , Bovinos , Técnicas de Química Sintética , Citoproteção/efeitos dos fármacos , Composição de Medicamentos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Hidrólise , Masculino , Camundongos , Piroxicam/síntese química , Piroxicam/metabolismo , Pró-Fármacos/metabolismo , Ratos , Estômago/citologia , Úlcera Gástrica/prevenção & controle
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