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1.
Life Sci ; 259: 118272, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32800836

RESUMO

AIM: Vanadium, a trace element found in food and water sources has been previous reported to attenuate ulcer formation without much insight into its mechanism of action. This study highlights the mechanism by which vanadium exhibits its gastro-protective activity. MAIN METHODS: Eighty male Wistar rats (80-100 g) were randomized into 8 equal groups. Groups 1 (control) and 2 (Ulcerated control) received water only, groups 3-8 received vanadium at 5, 10, 25, 50, 100 and 200 ppm respectively in their drinking water for ten weeks. Gastric ulcer was thereafter induced in groups (2-8) via ischaemia-reperfusion (IR) technique. The stomachs were excised for macroscopic examination, evaluation of mucous content, oxidative stress markers, hydrogen/potassium (H+/K+) and calcium (Ca++) ATPases activities plus expression of induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Vanadium at low doses inhibited IR induced gastric ulcer by 62.62% (10 ppm), 54.80% (25 ppm) and 43.50% (50 ppm). KEY FINDINGS: Low dose vanadium increased mucous content, superoxide dismutase, catalase, glutathione activities and nitrite concentrations compared to ulcerated control group. The observed increase in malondialdehyde, Ca++ and H+/K+ ATPase activities, iNOS and COX-2 expression following IR were significantly reduced by pretreatment with vanadium. SIGNIFICANCE: This study demonstrated that vanadium at low doses exhibit gastro-protective activities on IR induced gastric ulcer in rat model by inhibiting proton pump activities and decreasing expressions of iNOS and COX-2, thereby giving more insight into the protective action of vanadium.


Assuntos
Traumatismo por Reperfusão/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Vanádio/farmacologia , Animais , Catalase/metabolismo , Ciclo-Oxigenase 2/metabolismo , Mucosa Gástrica/metabolismo , Masculino , Malondialdeído/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo , Bombas de Próton/efeitos dos fármacos , Ratos , Ratos Wistar , Reperfusão , Estômago/fisiologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Superóxido Dismutase/metabolismo
2.
Chem Biol Interact ; 327: 109166, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32531310

RESUMO

Boldine is the main alkaloid of Peumus boldus Molina, widely used in the traditional medicine for the treatment of digestive disorders. It is a compound with excellent antioxidant and anti-inflammatory properties already described. Despite the widespread use of P. boldus for digestive disorders treatment, the gastroprotective effect of Boldine remains unknown. Considering the need for new approaches to treat gastric ulcers with fewer side effects than current therapy, this study aimed to investigate the gastroprotective effect of Boldine in mice, as well as the mechanisms underlying this effect. The gastroprotective effect of Boldine was evaluated on gastric ulcer induced by 60% ethanol/0.3 M HCl or indomethacin (100 mg/kg) in mice. Histological analysis and the mucin-like glycoprotein content were evaluated in ethanol-ulcerated tissue, as well as, oxidative stress and inflammatory parameters. The mechanisms involved in the effect of Boldine were evaluated by pretreating mice with NEM (a sulfhydryl group chelator, 10 mg/kg, i.p.), l-NAME (a non-selective nitric oxide synthase inhibitor, 70 mg/kg, i.p.), yohimbine (an alpha-adrenergic receptor antagonist, 2 mg/kg, i.p.) and indomethacin (a cyclooxygenase inhibitor, 10 mg/kg, i.p.). In addition, the in vitro effect of Boldine on H+/K+-ATPase activity was determined. Boldine was able to protect gastric mucosa against the damage induced by ethanol/HCl and indomethacin, as evidenced by reduced lesion area and histological analysis. Moreover, the alkaloid reduced oxidative stress and inflammatory mediators in ethanol-ulcerated tissue, beyond has increased mucin-like glycoprotein amount. Finally, Boldine effect is dependent on non-protein sulfhydryl groups and prostanoids but does not involve the inhibition of H+/K + -ATPase activity, being a promising natural resource for gastric ulcer treatment.


Assuntos
Antiulcerosos/farmacologia , Aporfinas/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Úlcera Gástrica/prevenção & controle , Animais , Etanol , Feminino , Mucosa Gástrica/patologia , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Indometacina , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Prostaglandinas/metabolismo , Coelhos , Úlcera Gástrica/induzido quimicamente , Compostos de Sulfidrila/metabolismo
3.
AAPS PharmSciTech ; 21(5): 137, 2020 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-32419124

RESUMO

In the global incidence of peptic ulcer, with the associated rates of hospitalizations and mortality are increasing, in the United States, peptic ulcer disease affects approximately 4.6 million people annually, with an estimated 10% of the US population having evidence of a duodenal ulcer. The present research aims to find a novel treatment for ethanol induced ulcer by loading thymoquinone (TQ) on a nanostructured lipid carrier (NLC), using Compritol® 888 and coconut oil. The TQ-loaded coconut oil NLC was formulated using melt emulsification combined with a sonication method using Poloxamer 188 as a surfactant. Finally, the optimization of the formulations was performed on a three-factor, three-level Box-Behnken statistical design, with 85.63% entrapment efficiency of TQ in the optimized formulation. A biphasic release pattern of the formulation was recorded in an in vitro drug release study, where the initial burst release of the drug was observed in the first 2 h, followed by a gradual release. Later, the TQ-loaded coconut oil NLC was found to protect the gastric mucous membrane more effectively (78.95% in.; p < 0.01) in an alcohol-induced ulcer model, whereas the TQ suspension showed 30.87% inhibition (p < 0.05) of the ulcerative index, when compared with the ulcer control group. The histopathological evaluations of the stomach in ulcer-induced animals demonstrated protection potential of TQ-loaded coconut oil NLC against an alcohol-induced gastric ulcer. In a nutshell, the entrapment of TQ within the NLC was found to deliver the entrapped drug more effectively when administered through an oral route to possess a gastroprotective effect.


Assuntos
Benzoquinonas/administração & dosagem , Óleo de Coco/química , Etanol , Lipídeos/química , Nanoestruturas/química , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Animais , Benzoquinonas/química , Portadores de Fármacos , Emulsões , Ácidos Graxos , Masculino , Tamanho da Partícula , Poloxâmero , Ratos , Ratos Sprague-Dawley , Sonicação , Tensoativos
4.
Int J Mol Sci ; 21(7)2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32276345

RESUMO

Gastric ulcer (GU), a prevalent digestive disease, has a high incidence and is seriously harmful to human health. Finding a natural drug with a gastroprotective effect is needed. Ocotillol, the derivate of ocotillol-type saponins in the Panax genus, possesses good anti-inflammatory activity. The study aimed to investigate the gastroprotective effect of ocotillol on acetic acid-induced GU rats. The serum levels of endothelin-1 (ET-1) and nitric oxide (NO), the gastric mucosa levels of epidermal growth factor, superoxide dismutase and NO were assessed. Hematoxylin and eosin staining of gastric mucosa for pathological changes and immunohistochemical staining of ET-1, epidermal growth factor receptors and inducible nitric oxide synthase were evaluated. A UPLC-QTOF-MS-based serum metabolomics approach was applied to explore the latent mechanism. A total of 21 potential metabolites involved in 7 metabolic pathways were identified. The study helps us to understand the pathogenesis of GU and to provide a potential natural anti-ulcer agent.


Assuntos
Anti-Inflamatórios/farmacologia , Ginsenosídeos/farmacologia , Metabolômica , Úlcera Gástrica/prevenção & controle , Ácido Acético/toxicidade , Animais , Anti-Inflamatórios/uso terapêutico , Antiulcerosos/farmacologia , Endotelina-1/sangue , Ginsenosídeos/uso terapêutico , Masculino , Óxido Nítrico/sangue , Ratos , Ratos Wistar , Úlcera Gástrica/sangue , Úlcera Gástrica/induzido quimicamente
5.
Int J Nanomedicine ; 15: 1187-1203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32110016

RESUMO

Background: Selenium (Se) is an indispensable trace element required for animals and human beings, whereas Se-deficiency can accelerate the development of acute gastric injury induced by over-consumption of alcohol. Selenium nanoparticles (SeNPs), as a special Se-supplement with favorable properties and unique bioactivities, are expected to play a passive role in gastroprotection. To the best of our knowledge, the gastroprotective potential of SeNPs is unknown and also, a rapid preparation of orally stable SeNPs available for prospective commercial application in the clinic is needed. Thus, SeNPs-embedded chitosan microspheres (SeNPs-CM) were developed to deliver SeNPs, and their gastroprotective potential was evaluated. Results: Herein, a rapid, eco-friendly and economic preparation process, composed of synthesis of SeNPs decorated by chitosan (CS), purification of CS-SeNPs by ultra-filtration (UF) and spray-drying of the purified CS-SeNPs, was introduced to prepare SeNPs-CM. The uniformly distributed SeNPs with a nanosize range of 60 nm were loaded into CS-microspheres, and they could be released from the microspheres in gastric conditions. In addition, SeNPs-CM were safer than selenite in terms of Se dose, with a LD50 of around 8-fold of that of selenite, and it could efficiently enhance the Se retention in Se-deficient Wistar rats. Furthermore, SeNPs-CM pre-treatment might significantly attenuate the ethanol-induced gastric mucosal damage, based on histological evaluation. It might be partly attributed to the systematic antioxidant activities of SeNPs-CM, reflected by the reduction in lipid peroxidation, the augmentation in antioxidant enzymatic activity as well as decreasing aggressive nitric oxides (NO). Conclusion: SeNPs-CM could be taken into consideration as a prospective Se-supplement for the oral delivery of SeNPs, with prominent gastroprotective effect against ethanol-induced mucosal injury.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Mucosa Gástrica/efeitos dos fármacos , Microesferas , Nanopartículas/administração & dosagem , Selênio/farmacologia , Administração Oral , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Quitosana/química , Etanol/toxicidade , Mucosa Gástrica/metabolismo , Masculino , Nanopartículas/química , Ratos Wistar , Selênio/administração & dosagem , Selênio/química , Selênio/farmacocinética , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Ultrafiltração/métodos
6.
Chem Biol Interact ; 321: 108964, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32006539

RESUMO

Lupeol (1) was isolated from hexane branch extract of Maytenus salicifolia and the Lupeol stearate (2), Lupeol palmitate (3), Lupeol myristate (4), Lupeol laurate (5) and Lupeol caprylate (6) were obtained reacting 1 with an adequate carboxylic acid. Swiss mice were treated with vehicle, carbenoxolone or Lupeol esters before administration of ethanol/HCl or indomethacin. Additionally, the involvement of nitric oxide (NO), sulfhydryl compounds (NP-SH), α-2 adrenergic receptors (α2-AR) and prostaglandins (PGE) in antiulcer effects was investigated using appropriate inhibitors or antagonist. Oxidative and inflammatory parameters were measured after euthanasia and anti-secretory effects was evaluated in pylorus-ligated rats. Ethanol/HCl ulcerated the gastric mucosa by 64.45 ± 6.58 mm2, which the oral treatment with 1, 4 and 6 (10 mg/kg), and 3 and 5 (30 mg/kg) reduced the lesion area. Interestingly, 2 reduced the gastric ulcer by oral route in a potent and dose-dependent manner (ED50 = 0.40 mg/kg), which was accompanied by the increase in reduced glutathione levels and by the reduction of lipids peroxidation and myeloperoxidase and superoxide dismutase activities. Moreover, 2 (0.1 mg/kg) also prevented the ulcerogenesis by intraperitoneal route. The participation of NO, NP-SH, α2-AR and PGE in 2-mediated gastroprotection was confirmed. In indomethacin-induced ulcer, 2 (1 mg/kg, p.o) also reduced the ulcer area and increased the PGE2 levels. However, 2 did not alter the gastric acid secretion. Therefore, these findings indicate that the obtention of 2 potentiated the antiulcer activity of 1 and that this compound can elicit gastroprotective action due a diversified mode of action.


Assuntos
Antiulcerosos/farmacologia , Triterpenos Pentacíclicos/farmacologia , Úlcera Gástrica/prevenção & controle , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/química , Modelos Animais de Doenças , Esterificação , Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Ácido Clorídrico/toxicidade , Indometacina/toxicidade , Camundongos , NG-Nitroarginina Metil Éster/metabolismo , Óxido Nítrico/metabolismo , Triterpenos Pentacíclicos/administração & dosagem , Triterpenos Pentacíclicos/química , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Relação Estrutura-Atividade
7.
Acta Biochim Biophys Sin (Shanghai) ; 52(1): 26-37, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31889181

RESUMO

Chlorine is shown to possess anti-gastric ulcer activity, since it can inactivate Helicobacter pylori, which is regarded as one of the most common risk factors for causing gastric problems. In the current study, the gastroprotective property of a novel dichloro-substituted Schiff base complex, 2, 2'- [-1, 2-cyclohexanediylbis(nitriloethylidyne)] bis(4-chlorophenol) (CNCP), against alcohol-induced gastric lesion in SD rats was assessed. SD rats were divided into four groups, i.e. normal, ulcer control, testing, and reference groups. Ulcer area, gastric wall mucus, and also gastric acidity of the animal stomachs were measured. In addition, antioxidant activity of CNCP was evaluated and its safe dose was identified. Immunohistochemistry staining was also carried to evaluate two important proteins, i.e. Bcl2-associated X protein (Bax) and heat shock protein 70 (HSP70). Moreover, the activities of super oxide dismutase and catalase, as well as the levels of prostaglandin E2 (PGE2) and malondialdehyde (MDA) were also measured. Antioxidant activity of CNCP was approved via the aforementioned experiments. Histological evaluations showed that the compound possesses stomach epithelial defense activity. Additionally, periodic acid-Schiff staining exhibited over-expression of HSP70 and down-expression of Bax protein in the CNCP-treated rats. Moreover, CNCP caused deceased MDA level and elevated PGE2 level, and at the same time increased the activities of the two enzymes.


Assuntos
Antioxidantes/uso terapêutico , Proteínas de Choque Térmico HSP70/metabolismo , Bases de Schiff/toxicidade , Bases de Schiff/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Úlcera Gástrica/tratamento farmacológico , Proteína X Associada a bcl-2/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Catalase/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Clorofenóis/química , Dinoprostona/metabolismo , Modelos Animais de Doenças , Etanol/efeitos adversos , Etanol/farmacologia , Feminino , Fibroblastos/metabolismo , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Testes de Função Renal , Testes de Função Hepática , Masculino , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Bases de Schiff/química , Úlcera Gástrica/induzido quimicamente , Superóxido Dismutase/metabolismo
8.
Int J Mol Sci ; 21(3)2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31979417

RESUMO

Chrysin exhibits anti-inflammatory and antioxidant activities. Here, the gastroprotective effect of chrysin was investigated in mouse models of gastric ulcer induced by absolute ethanol, acetic acid, and ischemia-reperfusion injury. The gastric-healing effect was evaluated at 7 and 14 days after treatment; the mechanism of action was verified using the expression of metalloproteinase 2 (MMP-2) and 9 (MMP-9), caspase-3, cyclooxygenase 1 (COX-1) and 2 (COX-2), epidermal growth factor (EGF), and interleukin-10. Chrysin (10 mg/kg) inhibited macroscopic lesions and increased catalase activity in the mouse model established using absolute ethanol. It ameliorated the gastric ulcer caused by acetic acid by improving the expression of inflammatory genes such as COX-2, inhibiting negative remodeling promoted by MMP-9, increasing cell proliferation effect via EGF, and reducing cellular apoptosis by modulating caspase-3. A faster healing effect was evident in the first 7 days of treatment compared to 14 days of treatment, indicating the pharmacological potential of chrysin. Overall, these results demonstrate the potent effect of chrysin in the gastrointestinal tract and elucidate the genes involved in the healing of gastric ulcers. Moreover, an increase in the levels of gastric mucosa defensive factors is involved in the activity of chrysin in the gastric mucosa.


Assuntos
Antiulcerosos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Flavonoides/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Úlcera Gástrica/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Ácido Acético/toxicidade , Animais , Antiulcerosos/farmacologia , Apoptose/genética , Caspase 3/metabolismo , Catalase/metabolismo , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Etanol/toxicidade , Flavonoides/farmacocinética , Flavonoides/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Inflamação , Interleucina-10/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Oxirredução/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/enzimologia
9.
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
10.
J Ethnopharmacol ; 248: 112297, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31606535

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Members of the genus Erythrina have been traditionally used in the treatment of various ailments such as inflammation and gastrointestinal disorders. Erythrina speciosa (Fabaceae) is a spiny, deciduous shrub or small tree native to Southern America in Brazil. It is cultivated in Africa and Asia. The traditional usage of E. speciosa indicated its antibacterial, analgesic, and anti-inflammatory activities. AIM OF THE STUDY: Evaluation of the phytochemical constituents, gastroprotective effects and possible mechanism of action of the ethyl acetate fraction obtained from the methanol extract of E. speciosa leaves (ESLE). MATERIALS AND METHODS: Chemical characterization of ESLE was done using high performance liquid chromatography coupled to mass spectrometry (HPLC-MS). The gastroprotective activity of ESLE was evaluated using ethanol-induced gastric-ulcer model in rats. Rats were pre-treated with ESLE 25, 50 and 100 mg/kg 1 h before the administration of absolute ethanol. Histological analysis, mucin content, and total acidity were evaluated. The possible mechanism of action of ESLE was studied through the examination of oxidative stress and inflammatory markers, PGE2, and NF-κB, iNOS, COX-2, and HSP-70 immunoexpression. In vitro, anti-Helicobacter pylori activity of ESLE was also studied using micro-well dilution method. RESULTS: Fourteen compounds were tentatively identified including alkaloids, flavonoids, and saponins. ESLE exerted a powerful gastroprotective effect. The pre-treatment with ESLE at different doses resulted in a significant reduction in gastric lesions and significant elevation in the mucin production. These effects could be partially mediated by the potent anti-inflammatory activity of ESLE as evidenced by the significant reduction in the immunoexpression of NF-κB, COX-2, iNOS and the reduction in the pro-inflammatory marker, TNF-α. ESLE counteracted the ethanol-induced oxidative stress by increasing the levels of depleted GSH and catalase as well as significantly attenuating the ethanol-induced lipid peroxidation tissue levels. In addition, ESLE exhibited in vitro antibacterial activity against H. pylori. CONCLUSIONS: The chemical constituents of ESLE strongly support its potent gastroprotective effect suggesting its future potential application in the management of gastric ulcer by eliminating its symptoms and causes including H. pylori.


Assuntos
Antiulcerosos/uso terapêutico , Fabaceae , Extratos Vegetais/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Animais , Antiulcerosos/farmacologia , Ciclo-Oxigenase 2/metabolismo , Egito , Etanol , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/crescimento & desenvolvimento , Masculino , Mucinas/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta , Ratos Sprague-Dawley , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia
11.
Hum Exp Toxicol ; 39(4): 547-562, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31876185

RESUMO

Gastric ulcer (GU) is the most common health concern that occurs due to alcohol consumption, smoking and physiological stress. Ethanol-induced GU in animal model resembles the pathophysiology of human ulcer. The present study was designed to investigate the cytoprotective and anti-inflammatory properties of tert-butylhydroquinone (tBHQ), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator, against gastric mucosal damage induced by acute exposure of ethanol (5 ml/kg). The intervention of tBHQ (25 and 50 mg/kg, per os (po)) and omeprazole (20 mg/kg, po) was done for 10 consecutive days. Omeprazole was chosen as a standard drug because it is prescribed for the treatment of GU. Pretreatment of tBHQ decreased gastric mucosal lesion, ulcer index, apoptotic cells and lipid peroxidation level induced by ethanol. Furthermore, the intervention of tBHQ increased gastric mucosa integrity, pH, reduced glutathione, collagen and mucus-producing goblet cells. Intervention of tBHQ increased the expression of antioxidant markers such as Nrf2, haeme oxygenase-1 and catalase and decreased the expressions of inflammatory markers such as nuclear factor kappa-light-chain-enhancer of activated B cells and cyclooxygenase-2. The cytoprotective potential of tBHQ against gastric mucosal damage might be due to its ability to enhance cellular antioxidants and anti-inflammatory responses.


Assuntos
Antioxidantes/farmacologia , Etanol/toxicidade , Heme Oxigenase (Desciclizante)/metabolismo , Hidroquinonas/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Úlcera Gástrica/prevenção & controle , Animais , Modelos Animais de Doenças , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Masculino , Ratos Sprague-Dawley , Transdução de Sinais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo
12.
Oxid Med Cell Longev ; 2019: 1568720, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827668

RESUMO

Gastric ulcer is a painful lesion of the gastric mucosa which can be disabling, or even more very serious in the case of a perforation of the stomach and internal hemorrhage. Traditional pharmacopeias have shown the efficacy of various plant extracts in the treatment of this pathology. Some extracts from Opuntia ficus indica (OFI) have been proven to have medicinal therapeutic benefits. The aim of this study was to investigate the preventive and curative effects of OFI seed oil extracted by cold pressing on an ethanol-induced gastric ulcer model in rats. Gastroprotective activities of the oil were assessed as pretreatments prior to ethanol gavage of Wistar rats compared to reference drugs. Two oil dose effects were tested. Ulcer and gastric parameters were measured (ulcerated areas (mm2), % of ulcer inhibition, gastric juice volume and pH, and mucus weight). Macroscopical and microscopical assessments of the stomachs as well as gastric biopsy histological studies were carried out. OFI oil exhibited a high efficiency in the protection of the cytoarchitecture and function of the gastric mucosa against the severe damages provoked by ethanol intake. Ulcerated areas were very significantly reduced and the % of ulcer inhibition was the highest under OFI oil pretreatment. Mucus production was stimulated, gastric juice volume was reduced, and its pH was increased. Histopathological examination of H&E-stained biopsies collected from gastric mucosae from the different experimental groups confirmed the gastroprotective efficacy of OFI oil against ethanol-induced symptoms such as inflammation and damages like bleeding, erosions, lesions, necrosis, and ulcers. Furthermore, OFI oil treatment speeded-up the reduction of the surface of ethanol-induced ulcerated areas in a dose-dependent manner, leading to a time gain in the healing process. The healing rate reached 91% on day 2 and 99% on day 3, and a complete heal was attained at the fourth day under OFI oil treatment, while ulcer areas were still partially unhealed in all the other groups. The therapeutic effects of OFI oil against gastric ulcer could be mediated by its varied bioactive compounds that we have demonstrated in the analytical study. They could act synergistically or in a delayed manner to optimize the healing process through protective antioxidant properties, as well as an antagonism against histamine H2-receptors, a stimulation of the signaling pathways necessary for mucus and bicarbonate production, and reduction of inflammatory processes in the gastric mucosa. Additionally, OFI oil fatty acids (especially unsaturated) and triacylglycerols contribute to the reconstruction and the repair of the cell membrane lipid bilayer during the gastric ulcer healing process.


Assuntos
Opuntia/metabolismo , Óleos Vegetais/química , Substâncias Protetoras/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Antioxidantes/química , Cromatografia Gasosa , Etanol/toxicidade , Ácidos Graxos Insaturados/farmacologia , Flavonoides/análise , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Antagonistas dos Receptores Histamínicos H2/química , Antagonistas dos Receptores Histamínicos H2/farmacologia , Antagonistas dos Receptores Histamínicos H2/uso terapêutico , Masculino , Extratos Vegetais/química , Óleos Vegetais/farmacologia , Óleos Vegetais/uso terapêutico , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico , Ratos , Ratos Wistar , Receptores Histamínicos H2/química , Receptores Histamínicos H2/metabolismo , Sementes/metabolismo , Transdução de Sinais/efeitos dos fármacos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Úlcera Gástrica/prevenção & controle
13.
Oxid Med Cell Longev ; 2019: 1983137, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827669

RESUMO

Ethnomedicinal studies in the Amazon community and in the Northeast region of Brazil highlight the use of Libidibia ferrea fruits for the treatment of gastric problems. However, there are no data in the literature of this pharmacological activity. Thus, the aim of this paper is to provide a scientific basis for the use of the dry extract of L. ferrea pods (DELfp) for the treatment of peptic ulcers. Phytochemical characterization was performed by HPLC/MS. In vitro antioxidant activity was assessed using DPPH, ABTS, phosphomolybdenum, and superoxide radical scavenging activity. The gastroprotective activity, the ability to stimulate mucus production, the antisecretory activity, and the influence of -SH and NO compounds on the antiulcerogenic activity of DELfp were evaluated. The healing activity was determined by the acetic acid-induced chronic ulcer model. Anti-Helicobacter pylori activity was investigated. HPLC/MS results identified the presence of phenolic compounds, gallic acid and ellagic acid, in DELfp. The extract showed antioxidant activity in vitro. In ulcers induced by absolute ethanol and acidified ethanol, the ED50 values of DELfp were 113 and 185.7 mg/kg, respectively. DELfp (100, 200, and 400 mg/kg) inhibited indomethacin-induced lesions by 66.7, 69.6, and 65.8%, respectively. DELfp (200 mg/kg) reduced gastric secretion and H+ concentration in the gastric contents and showed to be independent of nitric oxide (NO) and dependent on sulfhydryl (-SH) compounds in the protection of the gastric mucosa. In the chronic ulcer model, DELfp reduced the area of the gastric lesion. DELfp also showed anti-H. pylori activity. In conclusion, DELfp showed antioxidant, gastroprotective, healing, and antiulcerogenic activities. The mechanism of these actions seems to be mediated by different pathways and involves the reduction of gastric secretion and H+ concentration, dependence on sulfhydryl compounds, and anti-H. pylori activity. All these actions support the medicinal use of this species in the management of peptic ulcers.


Assuntos
Antiulcerosos/química , Antioxidantes/química , Fabaceae/química , Extratos Vegetais/química , Ácido Acético/toxicidade , Animais , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Cromatografia Líquida de Alta Pressão , Fabaceae/metabolismo , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Helicobacter pylori/efeitos dos fármacos , Espectrometria de Massas , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Fenóis/análise , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Compostos de Sulfidrila/química , Compostos de Sulfidrila/metabolismo
14.
BMC Complement Altern Med ; 19(1): 345, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791313

RESUMO

BACKGROUND: Cuphea ignea is one of the herbal resources belonging to Lythraceae family. Some species of this family have been used traditionally in South and Central America's folk medicine for treating stomach disorders. Therefore, the present study was performed to evaluate the gastropreventive effect of aqueous ethanolic extract of C. ignea aerial parts on ethanol-induced gastric ulcer. METHODS: Gastric ulcers were induced in Sprague Dawley rats using one oral dose of absolute ethanol (1.5 mL/rat). The C. ignea aerial parts extract at doses of 250 and 500 mg/kg body weight and ranitidine (a reference drug) at a dose of 30 mg/kg body weight were orally administrated daily for 7 days before ulcer induction. One hour after ethanol administration blood samples were collected and then stomachs of sacrificed rats were subjected to biochemical, macroscopic and microscopic studies. RESULTS: Oral administration of C. ignea extract significantly attenuated gastric ulcer as revealed by significant reduction in the gastric ulcer index and volume of gastric juice while significantly increased preventive percentage, gastric pH value and pepsin activity. Pre-treatment of C. ignea extract markedly improved the serum level of TNF-α, the gastric MPO activity and NO content. Furthermore, C. ignea pre-treatment significantly increased the gastric levels of enzymatic and non- enzymatic antioxidants namely CAT, SOD, GSH-Px, and GSH with concomitant reduction in MDA level compared with those in the ethanol group. These results were further supported by histopathological findings which revealed the curing effect of C. ignea on the hemorrhagic shock induced by ethanol toxicity. CONCLUSIONS: C. ignea extract showed a potential gastroprotective effect on ethanol-induced gastric ulcer, and its effect may be mediated through suppression of oxidative stress and gastric inflammation.


Assuntos
Antiulcerosos/farmacologia , Antioxidantes/farmacologia , Cuphea , Extratos Vegetais/farmacologia , Úlcera Gástrica , Animais , Etanol/efeitos adversos , Feminino , Ratos , Ratos Sprague-Dawley , Estômago/efeitos dos fármacos , Estômago/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia
15.
Biomed Res Int ; 2019: 4921086, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31886219

RESUMO

This study aims to delineate the effects of Manilkara zapota Linn. (Sapodilla) fruit chloroform (Mz.CHCl3) and aqueous (Mz.Aq) extracts tested through different techniques. Antidiarrheal activity and intestinal fluid accumulation were examined by using castor oil-induced diarrhea and castor oil fluid accumulation models. Isolated rabbit jejunum tissues were employed for in vitro experiments. Antimotility and antiulcer were performed through charcoal meal transient time and ethanol-induced ulcer assay, molecular studies were conducted through proteomic analysis, and virtual screening was performed by using a discovery studio visualizer (DSV). Mz.CHCl3 and Mz.Aq extracts attributed dose-dependent (50-300 mg/kg) protection (20-100%) against castor oil-induced diarrhea and dose-dependently (50-300 mg/kg) inhibited intestinal fluid secretions in mice. Mz.CHCl3 and Mz.Aq extracts produce relaxation of spontaneous and K+ (80 Mm) induced contractions in isolated tissue preparations and decreased the distance moved by charcoal in the gastrointestinal transit model in rats. It showed gastroprotective effect in ulcerative stomach of rats and decreased levels of IL-18 quantified by proteomic analysis. Histopathological results showed ethanol-induced significant gastric injury, leading to cloudy swelling, hydropic degeneration, apoptosis, and focal necrosis in all gastric zones using hematoxylin and eosin (H&E) staining. Moreover, ethanol increased the activation and the expression of tumor necrotic factor (TNF-α), cyclooxygenase (COX-2), and nuclear factor kappa-light-chain-enhancer of activated B cells (p-NFκB). In silico results were comparative to in vitro results evaluated through virtual screening. Moreover, ethanol increased the activation and expression of tumor necrotic factor, cyclooxygenase, and nuclear factor kappa-light-chain-enhancer of activated B cells. This study exhibits the gastroprotective effect of Manilkara zapota extracts in the peritoneal cavity using a proteomic and in silico approach which reveals different energy values against target proteins, which mediate the gastrointestinal functions.


Assuntos
Antidiarreicos , Diarreia , Regulação da Expressão Gênica/efeitos dos fármacos , Manilkara/química , Extratos Vegetais , Proteoma/biossíntese , Proteômica , Úlcera Gástrica , Animais , Antidiarreicos/química , Antidiarreicos/farmacologia , Óleo de Rícino/efeitos adversos , Óleo de Rícino/farmacologia , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Diarreia/metabolismo , Diarreia/patologia , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Coelhos , Ratos , Ratos Sprague-Dawley , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia
16.
Nutrients ; 11(12)2019 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-31847337

RESUMO

We investigated the effects of enteral nutrition formula on non-steroidal anti-inflammatory drug (NSAID)-induced gastric lesions in mice. Male ICR mice aged 7-9 weeks old were fasted, then orally given either purified water, Mermed® One, or 2-fold diluted Terumeal® 2.0α as enteral nutrition (25 or 50 mL/kg each). Indomethacin (IND) was orally administered 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 the mice given enteral nutrition showed a significant, dose-dependent decrease compared to the purified water-treated group, and no significant difference was seen between the two enteral nutrition-treated groups. Comparable time courses of plasma IND concentrations suggest that enteral nutrition does not inhibit gastrointestinal absorption of IND. Our findings indicate that administering enteral nutrition could inhibit the onset of NSAID-induced gastric ulcers.


Assuntos
Nutrição Enteral , Alimentos Formulados , Indometacina/toxicidade , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Úlcera Gástrica/patologia
17.
Medicine (Baltimore) ; 98(48): e18142, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770250

RESUMO

RATIONALE: Mucormycosis is a rare opportunistic fungal infection with poor prognosis. The incidence of mucormycosis has been increasing, and it is a threat to immunocompromised hosts. We present a case of gastric mucormycosis complicated by a gastropleural fistula during immunosuppressive treatment for adult-onset Still disease (AOSD). PATIENT CONCERNS: An 82-year-old woman diagnosed with AOSD who developed gastric ulcers during the administration of an immunosuppressive therapy with corticosteroids, cyclosporine, and tocilizumab complained of melena and epigastralgia. Esophagogastroduodenoscopy showed multiple ulcers covered with grayish or greenish exudates. DIAGNOSES: The patient diagnosed with mucormycosis based on culture and biopsy of the ulcers, which showed nonseptate hyphae branching at wide angles. Mucor indicus was identified using polymerase chain reaction. INTERVENTIONS AND OUTCOMES: Although liposomal amphotericin B was administered, gastric mucormycosis was found to be complicated by a gastropleural fistula. The patient died because of pneumonia due to cytomegalovirus infection, and autopsy revealed the presence of Mucorales around the fistula connecting the stomach and diaphragm. LESSONS: Gastric mucormycosis is refractory to treatment and fatal. Surgical resection, if possible, along with antifungal drugs can result in better outcomes.


Assuntos
Fístula Gástrica/microbiologia , Mucormicose/complicações , Infecções Oportunistas/complicações , Fístula do Sistema Respiratório/microbiologia , Úlcera Gástrica/microbiologia , Idoso de 80 Anos ou mais , Feminino , Fístula Gástrica/induzido quimicamente , Humanos , Imunossupressores/efeitos adversos , Mucormicose/induzido quimicamente , Mucormicose/microbiologia , Infecções Oportunistas/induzido quimicamente , Infecções Oportunistas/microbiologia , Pleura/microbiologia , Fístula do Sistema Respiratório/induzido quimicamente , Doença de Still de Início Tardio/tratamento farmacológico , Úlcera Gástrica/induzido quimicamente
18.
BMC Med Genet ; 20(1): 183, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727004

RESUMO

BACKGROUND: It is well established that long-term use of aspirin can cause gastric mucosal injury. ACEIs and ARBs are inversely related to gastric ulcer development. This study aimed to evaluate the relationship between SLCO1B1 polymorphisms, which can affect ACEI and ARB transport, and gastric mucosal erosion in elderly male Chinese patients with cardiovascular disease who use aspirin. METHODS: Patients taking aspirin and an ACEI or ARB concomitantly who had undergone endoscopic screening for gastric erosion were analyzed for SLCO1B1 polymorphisms by a TaqMan assay. RESULTS: The frequency of the SLCO1B1*1b/*1b diplotype (42% vs. 24%; p = 0.002) was significantly higher in the gastric mucosal erosion group than in the control group. After adjustment for significant factors, SLCO1B1*1b/*1b (OR, 2.64; 95% CI, 1.59-4.17; p < 0.05) was found to be associated with gastric mucosal erosion in aspirin users. CONCLUSIONS: The presence of the SLCO1B1*1b/*1b diplotype may be a risk factor for aspirin-induced gastric mucosal erosion in elderly Chinese men taking aspirin and an ACEI or ARB concomitantly.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Aspirina/efeitos adversos , Mucosa Gástrica/patologia , Predisposição Genética para Doença , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/genética , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Aspirina/administração & dosagem , Estudos de Casos e Controles , China , Quimioterapia Combinada , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
19.
Int J Med Mushrooms ; 21(8): 805-816, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679287

RESUMO

The chaga medicinal mushroom (Inonotus obliquus) was traditionally used to treat various ailments. To establish the pharmacological properties of I. obliquus, studies were performed to show the antiulcer activity of the ethanolic extract. The ethanolic extract of I. obliquus was prepared. The antiulcer activity of I. obliquus was determined using gastric ulcerated rats (ulceration induced by ethanol). The ethanolic extract of I. obliquus (200 mg/kg) did not cause any sign of toxicity or sensitivity to rats when the extracts were administered by oral feed. Oral administration of ethanolic extract of I. obliquus exhibited antiulcer activity in all models used. The ethanolic extract of I. obliquus showed an effective antiulcer activity, which could be due to the presence of various biologically active compounds. This confirmed the traditional uses of I. obliquus in the treatment of ailments.


Assuntos
Antiulcerosos/farmacologia , Antioxidantes/metabolismo , Basidiomycota/química , Misturas Complexas/farmacologia , Úlcera Gástrica/tratamento farmacológico , Agaricales , Animais , Antiulcerosos/isolamento & purificação , Catalase/metabolismo , Misturas Complexas/isolamento & purificação , Dinoprostona/metabolismo , Modelos Animais de Doenças , Etanol , Glutationa/metabolismo , Concentração de Íons de Hidrogênio , Peroxidação de Lipídeos/efeitos dos fármacos , Medicina Tradicional , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Superóxido Dismutase/metabolismo
20.
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 Fármacos , 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 , ortoaminobenzoatos/farmacologia
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