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1.
Int J Nanomedicine ; 14: 4911-4929, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456637

RESUMO

Background: Apocynin (APO) is a bioactive phytochemical with prominent anti-inflammatory and anti-oxidant activities. Designing a nano-delivery system targeted to potentiate the gastric antiulcerogenic activity of APO has not been investigated yet. Chitosan oligosaccharide (COS) is a low molecular weight chitosan and its oral nanoparticulate system for potentiating the antiulcerogenic activity of the loaded APO has been described here. Methods: COS-nanoparticles (NPs) loaded with APO (using tripolyphosphate [TPP] as a cross-linker) were prepared by ionic gelation method and fully characterized. The chosen formula was extensively evaluated regarding in vitro release profile, kinetic analysis, and stability at refrigerated and room temperatures. Ultimately, the in vivo antiulcerogenic activity against ketoprofen (KP)-induced gastric ulceration in rats was assessed by macroscopic parameters including Paul's index and antiulcerogenic activity, histopathological examination, immunohistochemical (IHC) evaluation of cyclooxygenase-2 (COX-2) expression level in ulcerated gastric tissue, and biochemical measurement of oxidative stress markers and nitric oxide (NO) levels. Results: The selected NPs formula with COS (0.5 % w/v) and TPP (0.1% w/v) was the most appropriate one with drug entrapment efficiency percentage of 35.06%, particle size of 436.20 nm, zeta potential of +38.20 mV, and mucoadhesive strength of 51.22%. It exhibited a biphasic in vitro release pattern as well as high stability at refrigerated temperature for a 6-month storage period. APO-loaded COS-NPs provoked marvelous antiulcerogenic activity against KP-induced gastric ulceration in rats compared with free APO treated group, which was emphasized by histopathological, IHC, and biochemical studies. Conclusion: In conclusion, APO-loaded COS-NPs could be considered as a promising oral phytopharmaceutical nanoparticulate system for management of gastric ulceration.


Assuntos
Acetofenonas/administração & dosagem , Acetofenonas/farmacologia , Quitosana/química , Mucosa Gástrica/efeitos dos fármacos , Nanopartículas/química , Oligossacarídeos/química , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/farmacologia , Acetofenonas/uso terapêutico , Administração através da Mucosa , Animais , Biomarcadores/metabolismo , Varredura Diferencial de Calorimetria , Ciclo-Oxigenase 2/metabolismo , Liberação Controlada de Fármacos , Cinética , Masculino , Nanopartículas/ultraestrutura , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Estômago/efeitos dos fármacos , Estômago/patologia , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Suínos , Difração de Raios X
2.
Toxicol Lett ; 313: 150-158, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276768

RESUMO

Ochratoxin A (OTA), one of the most abundant food-contaminating mycotoxins, is a possible carcinogen to humans. We previously demonstrated that long-term (40 weeks) OTA exposure induces the malignant transformation of human gastric epithelium cells (GES-1) in vitro. However, the specific mechanism underlying OTA-induced gastric carcinogenesis is complex. In the present study, we used 2-DE and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI/TOF MS) combined with bioinformatics and immunoblotting to investigate the differentially expressed proteins between GES-1 and OTA-malignant transformed GES-1 cells (OTA-GES-1T cells) in vitro. We found that four differentially expressed proteins were identified after malignant transformation, including actin, cytoplasmic 1 (ACTB), F-actin-capping protein subunit alpha-1 (CAPZA1), Annexin A3 (ANXA3), thioredoxin peroxidase B from red blood cells (TPx-B) and Fibrinogen beta B (Fibrinogen ß). Among the differentially expressed proteins, the effect of Annexin A3 was analyzed by MTT assay, western blot, cell cycle analysis, wound healing assay, Transwell assay, and colony formation assay in OTA-GES-1T cells. The results showed that inhibition of Annexin A3 by siRNA effectively prevented the proliferation, migration, and invasion abilities of OTA-GES-1T cells. Collectively, the results of this study will guide future research on OTA carcinogenicity.


Assuntos
Anexina A3/metabolismo , Carcinógenos/toxicidade , Transformação Celular Neoplásica/induzido quimicamente , Células Epiteliais/efeitos dos fármacos , Mucosa Gástrica/efeitos dos fármacos , Ocratoxinas/toxicidade , Neoplasias Gástricas/induzido quimicamente , Anexina A3/genética , Western Blotting , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Biologia Computacional , Eletroforese em Gel Bidimensional , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Humanos , Invasividade Neoplásica , Proteômica/métodos , Transdução de Sinais/efeitos dos fármacos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
3.
Food Chem Toxicol ; 132: 110658, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31299295

RESUMO

This study was conducted to determine the effect of T-2 toxin on the transcriptome of the glandular stomach in chicks using RNA-sequencing (RNA-Seq). Four groups of 1-day-old Cobb male broilers (n = 4 cages/group, 6 chicks/cage) were fed a corn-soybean-based diet (control) and control supplemented with T-2 toxin at 1.0, 3.0, and 6.0 mg/kg, respectively, for 2 weeks. The histological results showed that dietary supplementation of T-2 toxin at 3.0 and 6.0 mg/kg induced glandular gastric injury including serious inflammation, increased inflammatory cells, mucosal edema, and necrosis and desquamation of the epithelial cells in the glandular stomach of chicks. RNA-Seq analysis revealed that there were 671, 1393, and 1394 genes displayed ≥2 (P < 0.05) differential expression in the dietary supplemental T-2 toxin at 1.0, 3.0, and 6.0 mg/kg, respectively, compared with the control group. Notably, 204 differently expressed genes had shared similar changes among these three doses of T-2 toxin. GO and KEGG pathway analysis results showed that many genes involved in oxidation-reduction process, inflammation, wound healing/bleeding, and apoptosis/carcinogenesis were affected by T-2 toxin exposure. In conclusion, this study systematically elucidated toxic mechanisms of T-2 toxin on the glandular stomach, which might provide novel ideas to prevent adverse effects of T-2 toxin in chicks.


Assuntos
Mucosa Gástrica/efeitos dos fármacos , Toxina T-2/toxicidade , Transcriptoma/efeitos dos fármacos , Administração Oral , Animais , Galinhas , Edema/induzido quimicamente , Mucosa Gástrica/patologia , Inflamação/induzido quimicamente , Masculino , Necrose/induzido quimicamente , RNA Mensageiro/metabolismo , Toxina T-2/administração & dosagem , Cicatrização/efeitos dos fármacos
4.
Chem Biol Interact ; 308: 45-50, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31095933

RESUMO

The flavonoid hesperidin is abundantly found in citrus fruits and is used to treat vascular diseases. Previous studies described its gastroprotective actions against stress or ethanol-induced ulcer in rodents; however, results from indomethacin-induced ulcer were controversy. Therefore, given its clinical use and contradictory findings in acute models, this study aims to evaluate the effect of hesperidin (1-10 mg/kg, p.o) on chronic gastric ulcer induced by acetic acid in rats, a model that resembles the ulcer in humans. Moreover, the effects of hesperidin on mucin levels and on inflammatory and oxidative parameters at ulcer site were also measured. The treatment with hesperidin at 3 and 10 mg/kg, once a day, by seven days, accelerated by 34 and 62%, respectively, the ulcer healing process when compared to vehicle-treated group (99.1 ±â€¯6.4 mm2). Histological and histochemistry analyses confirmed the healing effect with significant favoring of mucin production. Hesperidin also promoted the preservation of reduced glutathione levels in the gastric mucosa tissue, as well as the normalization of superoxide dismutase and catalase activities at similar levels to those found in the non-ulcerated group. In addition, flavonoid administration increased the enzymatic activity of glutathione-S-transferase by 35%. Tissue lipoperoxides and myeloperoxidase activity were reduced after hesperidin treatment. In conclusion, the flavonoid hesperidin revealed a gastric healing activity in the ulcerated mucosa, an effect that showed to be associated with the reduction of oxidative damage at ulcer site, due to the reduction of the neutrophil migration and the strengthening of the mucus barrier next to the mucosa.


Assuntos
Glicosídeos/uso terapêutico , Hesperidina/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Ácido Acético/toxicidade , Animais , Catalase/metabolismo , Esquema de Medicação , Flavanonas/química , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Glutationa/metabolismo , Glicosídeos/farmacologia , Hesperidina/farmacologia , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Superóxido Dismutase/metabolismo , Cicatrização/efeitos dos fármacos
5.
Biomed Res Int ; 2019: 4605748, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31111054

RESUMO

Background and Aims: Hydrotalcite plays an important role in the therapy of gastric ulcer induced by nonsteroidal anti-inflammatory drugs (NSAIDs), but little is known about the mechanism. We designed two experiments to study the preventive and curative effects of hydrotalcite on NSAIDs-related gastric injury in rats and to investigate the relationship between the protective and curative mechanism of hydrotalcite and the secretion of epidermal growth factor (EGF)/prostaglandin E2 (PGE2). Methods: Two experiments were separately designed to evaluate the preventive and curative effects of hydrotalcite. A total of 25 male rats and 25 female rats were randomly divided into five groups (vehicle group, model group, omeprazole group, hydrotalcite group, and ranitidine group) in each experiment. Rats were treated with indomethacin by gavage to build the model of acute gastric mucosal injury. The concentrations of EGF and PGE2 in blood specimens and mucosal injury indexes by gross inspection were measured and an immunohistochemical technique was also employed to test the levels of EGF, cyclooxygenase-1 (COX-1), and cyclooxygenase-2 (COX-2) in gastric mucosa. Results: Comparing with model group in both preventive and curative experiments, hydrotalcite decreased the gastric injury in the mucosa of stomach significantly (7±4.5 vs. 16±11.25, 1.5±2 vs. 2.5±6; P<0.01, P<0.05). The levels of EGF and PGE2 in blood serum were markedly higher in hydrotalcite group than that in model group and ranitidine group in preventive experiment (574.39±34.28 vs. 486.22±41.73, 488.07±24.44; P<0.01, P<0.01). The expression levels of COX-2 in gastric mucosa were also higher in hydrotalcite group than that in model group in both preventive and therapeutic experiments (12±4 vs. 9±6, 14±7 vs. 9±4; P<0.01, P<0.05). Conclusions: Hydrotalcite promotes gastric protection and healing via several mechanisms, including increased levels of PGE2 in blood serum, activation of EGF, and antagonising the inhibition of cyclooxygenase (COX) caused by NSAIDs.


Assuntos
Hidróxido de Alumínio/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/lesões , Indometacina/efeitos adversos , Hidróxido de Magnésio/farmacologia , Úlcera Gástrica/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/sangue , Dinoprostona/metabolismo , Modelos Animais de Doenças , Fator de Crescimento Epidérmico/sangue , Fator de Crescimento Epidérmico/metabolismo , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Masculino , Proteínas de Membrana/metabolismo , Omeprazol/farmacologia , Ranitidina/farmacologia , Ratos , Ratos Wistar , Estômago/efeitos dos fármacos , Úlcera Gástrica/patologia
6.
BMC Complement Altern Med ; 19(1): 91, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31035975

RESUMO

BACKGROUND: The extract of Celastrus orbiculatus (COE) have been studied for anti-Helicobacter pylori (H. pylori) activity and anti-cancer effects in vitro and in vivo. However, the molecular mechanism by which COE inhibits H. pylori-induced inflammatory response has not been fully elucidated so far. METHODS: The effects of COE on viability, morphological changes, inflammatory cytokine secretion, protein and mRNA expression were analyzed by MTT assay, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, western blot and real-time PCR (RT-PCR), respectively. The methylation level of programmed cell death 4 (PDCD4) promoter was investigated by methylation-specific PCR. (MSP) . RESULTS: COE effectively inhibited the H.pylori-induced inflammatory response by regulating epithelial-mesenchymal transition (EMT). The methylation level of PDCD4 promoter was suppressed by COE, which increased the expression ofPDCD4. Moreover, COE could inhibit microRNA-21 (miR-21) expression, as shown by an enhancement of its target gene PDCD4. Furthermore, both miR-21 over-expression and PDCD4 silencing attenuated the anti-inflammatory effect. of COE. CONCLUSIONS: COE inhibits H. pylori induced inflammatory response through regulating EMT, correlating with inhibition of miR-21/PDCD4 signal pathways in gastric epithelial cells.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Celastrus/química , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Helicobacter pylori , MicroRNAs/metabolismo , Extratos Vegetais/farmacologia , Proteínas de Ligação a RNA/metabolismo , Anti-Inflamatórios/farmacologia , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular , Citocinas/análise , Citocinas/metabolismo , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Mucosa Gástrica/citologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/imunologia , Helicobacter pylori/patogenicidade , Humanos , MicroRNAs/genética , Proteínas de Ligação a RNA/genética , Transdução de Sinais/efeitos dos fármacos
7.
Medicine (Baltimore) ; 98(20): e15710, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096520

RESUMO

BACKGROUND: To systematically evaluate efficacy of traditional Chinese medicine (TCM) in treating chronic gastritis (CG). METHODS: Data sources from PubMed, Embase, Springer Link, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Chinese Biomedicine Database, and Wan-fang database were searched up to July 5, 2018. Review Manager software version 5.3, the Cochrane Collaboration's risk of bias tool, and the Grading of Recommendations Assessment, Development, and Evaluation profiler software were conducted for this meta-analysis. RESULTS: Sixteen studies involving 1673 participants (906 vs 767) were included in this study. Pooled data showed significant statistical differences between TCM groups and current routine pharmacotherapy (RP) groups in overall clinical efficacy (odds ratio [OR] 4.65; 95% confidence interval [CI] 3.29, 6.56; P < .00001), efficacy under endoscopy (OR 2.46; 95% CI 1.12, 5.43; P = .03), stomach distension (mean difference [MD] -0.37; 95% CI -0.56, -0.19; P < .0001), stomachache (standardized MD [SMD] -0.80; 95% CI -1.45, -0.14; P = .02), and belching (SMD -2.00; 95% CI -3.80, -0.20; P = .03). However, acid regurgitation (SMD -0.71; 95% CI -1.69, 0.28; P = .16) and anorexia (SMD -0.75; 95% CI -2.30, 0.80; P = .35) showed no significant statistical differences between 2 groups. In addition, incidence of adverse reactions of TCM groups was lower than that of RP groups. CONCLUSION: Evidence from this meta-analysis suggests that TCM could be more efficacious than current RP in treating CG. But further standardized research of rigorous design should be needed to further validate its efficacy.


Assuntos
Mucosa Gástrica/efeitos dos fármacos , Gastrite/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Doença Crônica , Endoscopia do Sistema Digestório/métodos , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/patologia , Gastrite/diagnóstico por imagem , Gastrite/patologia , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
8.
Cell Mol Biol (Noisy-le-grand) ; 65(3): 76-83, 2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30942158

RESUMO

The aim of this study is an investigation the protective effects of vitamin C (Vit C), vitamin E (Vit E), ß-carotene, sodium selenate combination in indomethacin-induced gastric mucosal damage in rats. Rats were divided into 6 groups. Group I: Intact animals (control). Group II: Control animals receiving Vit C (100 mg/kg/day), Vit E (100 mg/kg/day), ß-carotene (15 mg/kg/day) and sodium selenate (0.2 mg/kg/day) for 3 days. Group III: Animals receiving 25 mg/kg indomethacin. Group IV: Animals receiving Vit C, Vit E, ß-carotene and sodium selenate (in same doses) for 3 days 2 h before the administration of indomethacin. Group V: Animals receiving ranitidine (150 mg/kg) for 3 days. Group VI: Animals receiving ranitidine for 3 days 2 h before to the administration of indomethacin (in same dose and time). The administration of indomethacin caused a decrease in the levels of glutathione, mucus, hexosamine and in the activities of glutathione-S-transferase, sodium-potassium ATPase, thromboplastic activity and an increase in the aspartate and alanine amino transferase, alkaline phosphatase, catalase, lactate dehydrogenase, myeloperoxidase activities and sialic acid, lipid peroxidation and protein carbonyl levels.  Stomach caspase-8 immun+ cell numbers showed a slight increase while caspase-9 immun+ cell numbers reduced in indomethacin given group compared to control animals. Our results findings suggest that the combination of Vit C, Vit E, ß-carotene, sodium selenate and ranitidine has a protective effect on indomethacin-induced gastric mucosal injury of rats.


Assuntos
Antioxidantes/farmacologia , Mucosa Gástrica/lesões , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Caspases/metabolismo , Catalase/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/enzimologia , Mucosa Gástrica/patologia , Glutationa/sangue , Glutationa Transferase/metabolismo , Hexosaminas/metabolismo , Indometacina , L-Lactato Desidrogenase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Mucinas/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Peroxidase , Ratos Sprague-Dawley , ATPase Trocadora de Sódio-Potássio/metabolismo
9.
Int J Mol Sci ; 20(8)2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-31003453

RESUMO

BACKGROUND: Helicobacter pylori (H. pylori) eradication therapy may improve gastric atrophy and intestinal metaplasia, but the results of previous studies have not always been consistent. The aim of this study was to compare the histological changes of intestinal metaplasia and gastric atrophy among the use of acid-suppressing drugs after H. pylori eradication. METHODS: A cohort of 242 patients who underwent successful eradication therapy for H. pylori gastritis and surveillance endoscopy examination from 1996 to 2015 was analyzed. Changes in the histological scores of intestinal metaplasia and atrophy according to drug use (proton-pump inhibitors (PPIs), H2 receptor antagonists (H2RAs), and non-acid suppressant use) were evaluated in biopsies of the antrum and corpus using a generalized linear mixed model in all patients. RESULTS: The mean follow-up period and number of biopsies were 5.48 ± 4.69 years and 2.62 ± 1.67 times, respectively. Improvement in the atrophy scores of both the antrum (p = 0.042) and corpus (p = 0.020) were significantly superior in patients with non-acid suppressant drug use compared with those of PPI and H2RA use. Metaplasia scores in both the antrum and corpus did not improve in all groups, and no significant differences were observed among groups in the antrum (p = 0.271) and corpus (p = 0.077). CONCLUSIONS: Prolonged acid suppression by PPIs or H2RAs may limit the recovery of gastric atrophy following H. pylori eradication.


Assuntos
Atrofia/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Inibidores da Bomba de Prótons/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia/microbiologia , Atrofia/fisiopatologia , Atrofia/prevenção & controle , Endoscopia , Feminino , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/microbiologia , Mucosa Gástrica/fisiopatologia , Gastrite/tratamento farmacológico , Gastrite/microbiologia , Gastrite/fisiopatologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/fisiopatologia , Helicobacter pylori/metabolismo , Helicobacter pylori/patogenicidade , Humanos , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Intestinos/fisiopatologia , Masculino , Metaplasia/tratamento farmacológico , Metaplasia/microbiologia , Metaplasia/fisiopatologia , Pessoa de Meia-Idade
12.
Psychopharmacology (Berl) ; 236(5): 1513-1530, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30982128

RESUMO

Pathological substance use disorders represent a major public health crisis with limited effective treatment options. While much work has been done to understand the neuronal signaling networks and intracellular signaling cascades associated with prolonged drug use, these studies have yielded few successful treatment options for substance use disorders. In recent years, there has been a growing interest to explore interactions between the peripheral immune system, the gut microbiome, and the CNS. In this review, we will present a summary of existing evidence, suggesting a potential role for gut dysbiosis in the pathogenesis of substance use disorders. Clinical evidence of gut dysbiosis in human subjects with substance use disorder and preclinical evidence of gut dysbiosis in animal models of drug addiction are discussed in detail. Additionally, we examine how changes in the gut microbiome and its metabolites may not only be a consequence of substance use disorders but may in fact play a role in mediating behavioral response to drugs of abuse. While much work still needs to be done, understanding the interplay of gut microbiome in substance use disorders may offer a promising avenue for future therapeutic development.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Transtornos Relacionados ao Uso de Substâncias/imunologia , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Analgésicos Opioides/efeitos adversos , Animais , Disbiose/induzido quimicamente , Disbiose/imunologia , Disbiose/metabolismo , Disbiose/psicologia , Etanol/efeitos adversos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/imunologia , Mucosa Gástrica/metabolismo , Humanos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Transtornos Relacionados ao Uso de Substâncias/psicologia
13.
Biomed Res ; 40(2): 87-95, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30982804

RESUMO

Helicobacter pylori (H. pylori) urease is a key protein for persistent infection of the bacteria in the stomach. Although H. pylori generally induce anti-H. pylori-specific antibodies (Abs), these Abs do not usually work for eradication or prevention of the H. pylori infection. In our previous study, we identified a linear epitope composed of 19-mer peptides termed UB-33, CHHLDKSIKEDVQFADSRI, within the large subunit of H. pylori urease. Anti-UB-33-specific Abs neutralized the enzymatic activity of H. pylori urease in vitro. In the present study, we evaluated the effect of immunization of BALB/c mice with H. pylori UB-33 peptide. After confirming the production of anti-UB-33-specific Abs, mice were challenged orally with H. pylori Sydney Strain-1 (SS-1). Mice producing anti-UB-33-specific Abs were not infected with SS-1, and the amount of SS-1 isolate in their stomach was significantly reduced. Also, the urease-negative mutant of H. pylori, HPP1801, did not colonize in the stomach, indicating that H. pylori urease was a critical element for infection of H. pylori in the gastric mucosa. Moreover, mice producing UB-33-specific Abs apparently suppressed H. pylori infection in the stomach where anti-UB-33 Abs were secreted in the gastric juice, indicating that H. pylori colonization was inhibited in the presence of anti-UB-33 Abs. In addition, the neutralization activity of sera from mice immunized with purified urease was less potent than that in the sera from mice immunized with UB-33. Furthermore, the recognition of epitope UB-33 was mediated through Toll-like receptor 2 (TLR2) on the B-1 cells using TLR2-knockout BALB/c mice in vivo. These results indicate that liner peptide UB-33 should be used for immunization to induce neutralizing Abs instead of purified H. pylori urease to prevent H. pylori infection and their colonization in the stomach.


Assuntos
Anticorpos Antibacterianos/biossíntese , Anticorpos Neutralizantes/biossíntese , Proteínas de Bactérias/imunologia , Infecções por Helicobacter/prevenção & controle , Imunização/métodos , Peptídeos/imunologia , Urease/imunologia , Sequência de Aminoácidos , Animais , Proteínas de Bactérias/genética , Epitopos/química , Epitopos/imunologia , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/imunologia , Mucosa Gástrica/microbiologia , Deleção de Genes , Expressão Gênica , Infecções por Helicobacter/genética , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/crescimento & desenvolvimento , Helicobacter pylori/imunologia , Soros Imunes/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos/administração & dosagem , Peptídeos/síntese química , Estômago/efeitos dos fármacos , Estômago/imunologia , Estômago/microbiologia , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/imunologia , Urease/deficiência , Urease/genética
14.
Nitric Oxide ; 88: 27-34, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30980891

RESUMO

Upon consumption, dietary nitrate is reduced to nitrite in the oral cavity and to nitric oxide (•NO) in the stomach. Here, •NO increases mucosal blood flow, mucus thickness and prevents microbial infections. However, the impact of nitrate on gut microbiota, a pleiotropic organism essential to maintain gastrointestinal and systemic welfare, remains elusive. This study investigates the impact of nitrate on gut microbiota profile and ensued mucosal effects during dysbiosis. Male Wistar rats were randomly distributed in 4 groups and the drinking water was supplemented for 7 days as follows: 1) antibiotic cocktail (neomycin, bacitracin and imipenem), 2) antibiotic cocktail + sodium nitrate, 3) sodium nitrate and 4) regular drinking water. Animals were weighted daily and feces were collected before and after the treatment. The stomach was isolated and the expression of occludin, claudin-5 as well as myeloperoxidase and iNOS was studied. Bacterial DNA was analyzed in fecal samples by PCR-DGGE genetic fingerprinting. Nitrate prevented antibiotic-induced body weight loss (1.9 ± 1.8% vs 8.9 ±â€¯1.8%, p < 0.05) and cecamegalia (7.1 ±â€¯0.5% vs 5.6 ±â€¯0.4%, p < 0.05). Gastric expression of occludin and claudin-5 tended to decrease during dysbiosis but both protein levels were recovered following nitrate consumption (p < 0.05). Similarly, nitrate inhibited the overexpression of myeloperoxidase and iNOS observed under dysbiosis (p < 0.05). Broad spectrum antibiotics significantly decreased microbiota richness and diversity in comparison to controls (p = 0.0016). After 7 days of treatment, whereas antibiotics reduced microbiota richness by 56%, it was observed that nitrate was able to prevent such microbial loss to only 48%, although without statistical differences (p = 0.068). This data suggests that dietary nitrate may be envisaged as a key component of functional foods with beneficial impact on gastric mucosal integrity during antibiotherapy but further studies are mandatory to better ascertain as to whether it modulates intestinal microbiota in terms of taxonomic and functional levels.


Assuntos
Claudina-5/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Nitratos/uso terapêutico , Óxido Nítrico Sintase Tipo II/metabolismo , Ocludina/metabolismo , Peroxidase/metabolismo , Animais , Antibacterianos , Sequência de Bases , Ceco/efeitos dos fármacos , Disbiose/induzido quimicamente , Fezes/microbiologia , Mucosa Gástrica/efeitos dos fármacos , Inflamação/metabolismo , Masculino , Ratos Wistar , Junções Íntimas/efeitos dos fármacos , Perda de Peso/efeitos dos fármacos
15.
Zhongguo Zhong Yao Za Zhi ; 44(1): 181-185, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-30868830

RESUMO

Chronic gastritis is a kind of chronic gastric mucosal inflammation caused by many factors.Intestinal metaplasia refers to the transformation of gastric mucosal epithelial cells into small/large intestinal mucosal epithelium containing Panette or goblet cells.Chronic gastritis has the highest incidence among stomach diseases,while intestinal metaplasia is the serious manifestation of chronic gastritis.In this experiment,the therapeutic effect of modified Zhengqi Powder on mild intestinal metaplasia in chronic gastritis and on patients' quality of life and inflammatory reaction was investigated to analyze the efficacy and mechanism of traditional Chinese medicine prescription.From April 2016 to April 2017,120 patients of chronic gastritis with mild intestinal metaplasia were selected and divided into two groups according to the envelope method.The control group(60 cases) was treated with famoxetine.After one month of continuous treatment,the total effective rate of treatment in the observation group was 93.3%,which was much higher than 80.0% in the control group.Health questionnaire(SF-36),serum C-reactive protein(CRP),interleukin-8(IL-8) and tumor necrosis factor-α(TNF-α) levels were significantly higher than those in the control group(P<0.05).The results showed that modified Zhengqi Powder has a significant efficacy in treat chronic gastritis with mild intestinal metaplasia,and can obviously alleviate clinical symptoms and intestinal metaplasia,remove inflammatory factors and improve the quality of life of patients,and is worth promotion.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Gastrite Atrófica/tratamento farmacológico , Proteína C-Reativa/análise , Mucosa Gástrica/efeitos dos fármacos , Humanos , Interleucina-8/sangue , Metaplasia/tratamento farmacológico , Qualidade de Vida , Fator de Necrose Tumoral alfa/sangue
16.
Pak J Pharm Sci ; 32(1(Supplementary)): 285-291, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30829205

RESUMO

It has been reported that specific microRNA could inhibit apoptosis of gastric mucosa. Our study was designed to investigate the effect and mechanisms of miR-145 in gastric mucosa. Gastric mucosal cells (GES-1) were treated with null-vector or miR-145 over expression plasmid. Cell viability was determined by CCK-8 assay and detection of apoptosis by flow cytometry. Autophagic and apoptosis protein expression and c-Jun NH2-terminal kinase (JNK) phosphorylation were determined by Western blotting. Autophagy response and JNK activities were inhibited by specific inhibitor, 3MA or SP600125, respectively. LDH release assay was used to detect cytotoxicity. We confirmed that miR-145 triggered an autophagic response in GES-1 cells and depended on JNK activation. Blocking autophagy or JNK activation with specific inhibitor, 3MA or SP600125, potentiated cell death and caspase-3 activation. Furthermore, we confirmed that miR-145 enhanced the viability of GES-1 cells, phosphorylation of JNK and inhibited apoptosis of gastric mucosal miR-145 inhibited apoptosis of gastric mucosal via up-regulating JNK-mediated cytoprotective autophag.


Assuntos
Apoptose/genética , Autofagia/genética , Mucosa Gástrica/efeitos dos fármacos , MAP Quinase Quinase 4/metabolismo , MicroRNAs/metabolismo , Antracenos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Células Cultivadas , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Humanos , Lipopolissacarídeos/farmacologia , MAP Quinase Quinase 4/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Regulação para Cima
17.
Int J Mol Sci ; 20(6)2019 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-30909623

RESUMO

Turmeric obtained from the rhizomes of Curcuma longa has been used in the prevention and treatment of many diseases since the ancient times. Curcumin is the principal polyphenol isolated from turmeric, which exhibits anti-inflammatory, antioxidant, antiapoptotic, antitumor, and antimetastatic activities. The existing evidence indicates that curcumin can exert a wide range of beneficial pleiotropic properties in the gastrointestinal tract, such as protection against reflux esophagitis, Barrett's esophagus, and gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs (NSAIDs) and necrotizing agents. The role of curcumin as an adjuvant in the treatment of a Helicobacter pylori infection in experimental animals and humans has recently been proposed. The evidence that this turmeric derivative inhibits the invasion and proliferation of gastric cancer cells is encouraging and warrants further experimental and clinical studies with newer formulations to support the inclusion of curcumin in cancer therapy regimens. This review was designed to analyze the existing data from in vitro and in vivo animal and human studies in order to highlight the mechanisms of therapeutic efficacy of curcumin in the protection and ulcer healing of the upper gastrointestinal tract, with a major focus on addressing the protection of the esophagus and stomach by this emerging compound.


Assuntos
Curcumina/farmacologia , Doenças do Esôfago/tratamento farmacológico , Doenças do Esôfago/etiologia , Substâncias Protetoras/farmacologia , Gastropatias/tratamento farmacológico , Gastropatias/etiologia , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Curcumina/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Doenças do Esôfago/diagnóstico , Doenças do Esôfago/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Humanos , Substâncias Protetoras/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Gastropatias/diagnóstico , Gastropatias/metabolismo , Estresse Fisiológico/efeitos dos fármacos
18.
Biomed Pharmacother ; 111: 1112-1123, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30841424

RESUMO

Byrsonima intermedia is a species of bush popularly used to treat gastrointestinal disorders, such as gastric ulcers, gastritis, and diarrhea. Previous studies have revealed that the methanolic crude extract of B. intermedia leaves has gastroprotective and healing properties. In this new study, we specifically investigated two purified partitions, ethyl acetate (EtOAc) and water (AcoAq), obtained from the crude extract to characterize the antiulcer effects of these two partitions and the mechanisms of action of this medicinal plant. The healing effects of these partitions on the gastric and duodenal mucosa were assessed after ischemia-reperfusion (I/R) or acetic acid-induced injury. The involvement of tumor necrosis factor-alpha (TNF-alpha), interleukin 1ß (IL-1ß), interleukin 10 (IL-10), and myeloperoxidase (MPO) activity and glutathione (GSH) levels were determined. The antibacterial activity against Helicobacter pylori was evaluated using microdilution methods. The phytochemical analysis of AcoAq revealed a predominance of oligomeric proanthocyanidins and galloyl quinic esters, whereas EtOAc was found to contain concentrated flavonoids. Both partitions led to a significant reduction in gastric lesions, but AcoAq was more effective than EtOAc with regard to anti-Helicobacter pylori activity in addition to protecting the gastric mucosa against ethanol, non-steroidal anti-inflammatory drugs (NSAIDs) and duodenal mucosal damage induced by cysteamine. Additionally, both partitions were associated with a significant increase in gastric and duodenal healing and increased gastric mucosal GSH content after damage induced by acetic acid. On the other hand, after 6 days of treatment, EtOAc was more effective than AcoAq in ameliorating gastric damage upon initiation of the gastric I/R, which was accompanied by a significant reduction in the activity of gastric mucosal MPO, IL 1-ß and TNF-alpha, as well as an elevation in IL-10 and GSH content. These results demonstrate that the oligomeric proanthocyanidins and galloyl quinic esters present in AcoAq were more effective in the prevention of gastric and duodenal ulcers due to the antioxidant effects of these compounds, whereas the flavonoids present in EtOAc were more effective due to their anti-inflammatory activity on the gastric and duodenal tissue. All these results confirm that the rich phytochemical diversity of B. intermedia contributes to the pharmacological actions of this medicinal plant on the gastrointestinal tract in addition to its activity against H. pylori.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Malpighiaceae/química , Úlcera Péptica/tratamento farmacológico , Animais , Antiulcerosos/farmacologia , Flavonoides/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Gastrite/tratamento farmacológico , Gastrite/metabolismo , Glutationa/metabolismo , Masculino , Medicina Tradicional/métodos , Úlcera Péptica/metabolismo , Compostos Fitoquímicos/farmacologia , Fitoterapia/métodos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Plantas Medicinais/química , Ratos , Ratos Wistar , Estômago/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
19.
Cells ; 8(3)2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30884758

RESUMO

Intestinal dysbiosis is linked to numerous gastrointestinal disorders, including inflammatory bowel diseases. It is a question of debate if coxibs, selective inhibitors of cyclooxygenase (COX)-2, cause dysbiosis. Therefore, in the present study, we aimed to determine the effect of long-term (four weeks) selective inhibition of COX-2 on the small intestinal microbiota in the rat. In order to avoid mucosal damage due to topical effects and inflammation-driven microbial alterations, rofecoxib, a nonacidic compound, was used. The direct inhibitory effect of rofecoxib on the growth of bacteria was ruled out in vitro. The mucosa-sparing effect of rofecoxib was confirmed by macroscopic and histological analysis, as well as by measuring the intestinal levels of cytokines and tight junction proteins. Deep sequencing of bacterial 16S rRNA revealed that chronic rofecoxib treatment had no significant influence on the composition and diversity of jejunal microbiota. In conclusion, this is the first demonstration that long-term selective inhibition of COX-2 by rofecoxib does not cause small intestinal dysbiosis in rats. Moreover, inhibition of COX-2 activity is not likely to be responsible per se for microbial alterations caused by some coxibs, but other drug-specific properties may contribute to it.


Assuntos
Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/metabolismo , Disbiose/patologia , Intestino Delgado/enzimologia , Intestino Delgado/patologia , Lactonas/farmacologia , Sulfonas/farmacologia , Animais , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Celecoxib/farmacologia , Dinoprostona/biossíntese , Disbiose/microbiologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Ratos Wistar , Fatores de Tempo
20.
PLoS One ; 14(2): e0211703, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30707717

RESUMO

Alcohol binge drinking is a dangerous drinking habit, associated with neurological problems and inflammation. The impact of a single alcohol binge on innate immunity, gut barrier and gut microbiome was studied. In this cohort study 15 healthy volunteers received 2 ml vodka 40% v/v ethanol/kg body weight. Neutrophil function was studied by flow cytometry; markers of gut permeability and inflammation (lactulose/mannitol/sucrose test, zonulin, calprotectin, diamino-oxidase) were studied with NMR spectroscopy and enzyme-linked immunosorbent assay in urine, stool and serum respectively. Bacterial products in serum were quantified using different reporter cell lines. Gut microbiome composition was studied by 16S rDNA sequencing and bioinformatics analysis. After a single alcohol binge, neutrophils were transiently primed and the response to E.coli stimulation with reactive oxygen species (ROS) production was transiently increased, on the other hand the percentage of neutrophils that did not perform phagocytosis increased. No changes in gut permeability, inflammatory biomarker, bacterial translocation and microbiome composition could be detected up to 4 hours after a single alcohol binge or on the next day. A single alcohol binge in young, healthy volunteers transiently impacts on neutrophil function. Although the exact biological consequence of this finding is not clear yet, we believe that this strengthens the importance to avoid any alcohol binge drinking, even in young, otherwise healthy persons.


Assuntos
Bebedeira/complicações , Bebedeira/imunologia , Neutrófilos/efeitos dos fármacos , Adulto , Estudos de Coortes , Etanol/metabolismo , Fezes/microbiologia , Mucosa Gástrica/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Voluntários Saudáveis , Humanos , Inflamação/complicações , RNA Ribossômico 16S/análise , Adulto Jovem
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