Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.486
Filtrar
1.
J Enzyme Inhib Med Chem ; 35(1): 85-95, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31707866

RESUMO

To develop novel anti-inflammatory agents, a series of 5-alkyl-4-oxo-4,5-dihydro-[1, 2, 4]triazolo[4,3-a]quinoxaline-1-carboxamide derivatives were designed, synthesised, and evaluated for anti-inflammatory effects using RAW264.7 cells. Structures of the synthesised compounds were determined using 1H NMR, 13 C NMR, and HRMS. All the compounds were screened for anti-inflammatory activity based on their inhibitory effects against LPS-induced NO release. Among them, 5-(3,4,5-trimethoxybenzyl)-4-oxo-4,5-dihydro-[1, 2, 4]triazolo[4,3-a]quinoxaline-1-carboxamide (6p) showed the highest anti-inflammatory activity and inhibited NO release more potently than the lead compound D1. Further studies revealed that compound 6p reduced the levels of NO, TNF-α, and IL-6, and that its anti-inflammatory activity involves the inhibition of COX-2 and iNOS and downregulation of the mitogen-activated protein kinases (MAPK) signal pathway. Notably, compound 6p displayed more prominent anti-inflammatory activity than D1 and the positive control ibuprofen in the in vivo acute inflammatory model. Overall, these findings indicate that compound 6p is a therapeutic candidate for the treatment of inflammation.


Assuntos
Amidas/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Antiulcerosos/farmacologia , Descoberta de Drogas , Quinoxalinas/farmacologia , Úlcera Gástrica/tratamento farmacológico , Amidas/síntese química , Amidas/química , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antiulcerosos/síntese química , Antiulcerosos/química , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Relação Dose-Resposta a Droga , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Quinoxalinas/síntese química , Quinoxalinas/química , Células RAW 264.7 , Ratos , Úlcera Gástrica/metabolismo , Relação Estrutura-Atividade
2.
Mini Rev Med Chem ; 19(15): 1219-1254, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31735158

RESUMO

Nowadays, heterocyclic compounds act as a scaffold and are the backbone of medicinal chemistry. Among all of the heterocyclic scaffolds, 1,4-Dihydropyridine (1,4-DHP) is one of the most important heterocyclic rings that possess prominent therapeutic effects in a very versatile manner and plays an important role in synthetic, medicinal, and bioorganic chemistry. The main aim of the study is to review and encompass relevant studies related to 1,4-DHP and excellent therapeutic benefits of its derivatives. An extensive review of Pubmed-Medline, Embase and Lancet's published articles was done to find all relevant studies on the activity of 1,4-DHP and its derivatives. 1,4-DHP is a potent Voltage-Gated Calcium Channel (VGCC) antagonist derivative which acts as an anti-hypertensive, anti- anginal, anti-tumor, anti-inflammatory, anti-tubercular, anti-cancer, anti-hyperplasia, anti-mutagenic, anti-dyslipidemic, and anti-ulcer agent. From the inferences of the study, it can be concluded that the basic nucleus, 1,4-DHP which is a voltage-gated calcium ion channel blocker, acts as a base for its derivatives that possess different important therapeutic effects. There is a need of further research of this basic nucleus as it is a multifunctional moiety, on which addition of different groups can yield a better drug for its other activities such as anti-convulsant, anti-oxidant, anti-mutagenic, and anti-microbial. This review would be significant for further researches in the development of several kinds of drugs by representing successful matrix for the medicinal agents.


Assuntos
Di-Hidropiridinas/farmacologia , Compostos Heterocíclicos/farmacologia , Neoplasias/tratamento farmacológico , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Antiulcerosos/química , Antiulcerosos/farmacologia , Anti-Hipertensivos/química , Anti-Hipertensivos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Bloqueadores dos Canais de Cálcio/química , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/metabolismo , Di-Hidropiridinas/química , Compostos Heterocíclicos/química , Úlcera/tratamento farmacológico
3.
Int J Nanomedicine ; 14: 7191-7213, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564873

RESUMO

Background: Diosmin showed poor water solubility and low bioavailability. Poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles were successfully used to improve the drugs solubility and bioavailability. Coating of PLGA nanoparticles with chitosan can ameliorate their gastric retention and cellular uptake. Methodology: PLGA nanoparticles of diosmin were prepared using different drug and polymer amounts. Nanoparticles were selected based on entrapment efficiency% (EE%) and particle size measurements to be coated with chitosan. The selected nanoparticles either uncoated or coated were evaluated regarding morphology, ζ-potential, solid-state characterization, in vitro release, storage stability, and mucoadhesion. The anti-ulcer activity (AA) against ethanol-induced ulcer in rats was assessed through macroscopical evaluation, histopathological examination, immunohistochemical localization of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transmission electron microscopic examination of gastric tissues compared to free diosmin (100 mg/kg) and positive control. Results: Based on EE% and particle size measurements, the selected nanoparticles, either uncoated or coated with 0.1% w/v chitosan, were based on 1:15 drug-PLGA weight ratio and 20 mg diosmin employing methylene chloride as an organic phase. Examination by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed nanoscopic spherical particles. Drug encapsulation within the selected nanoparticles was suggested by Fourier transform-infrared, differential scanning calorimetry (DSC) and X-ray diffractometry results. Chitosan-coated nanoparticles were more stable against size enlargement probably due to the higher ζ-potential. Only coated nanoparticles showed gastric retention as revealed by SEM examination of stomach and duodenum. The superior AA of coated nanoparticles was confirmed by significant reduction in average mucosal damage, the majority of histopathological changes and NF-κB expression in gastric tissue when compared to positive control, diosmin and uncoated nanoparticles as well as insignificant difference relative to normal control. Coated nanoparticles preserved the normal ultrastructure of the gastric mucosa as revealed by TEM examination. Conclusion: The optimized chitosan-coated PLGA nanoparticles can be represented as a potential oral drug delivery system of diosmin.


Assuntos
Antiulcerosos/uso terapêutico , Quitosana/química , Diosmina/uso terapêutico , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Estômago/patologia , Úlcera/tratamento farmacológico , Adesividade , Animais , Antiulcerosos/farmacologia , Varredura Diferencial de Calorimetria , Diosmina/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Duodeno/efeitos dos fármacos , Duodeno/patologia , Duodeno/ultraestrutura , Mucosa Gástrica/patologia , Mucosa Gástrica/ultraestrutura , Cinética , Masculino , Muco/química , NF-kappa B/metabolismo , Nanopartículas/ultraestrutura , Tamanho da Partícula , Ratos Sprague-Dawley , Espectroscopia de Infravermelho com Transformada de Fourier , Estômago/efeitos dos fármacos , Estômago/ultraestrutura , Úlcera/patologia , Difração de Raios X
4.
Int J Clin Pharmacol Ther ; 57(11): 552-560, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31397275

RESUMO

OBJECTIVE: This study was conducted to evaluate the difference in acid inhibition function among lansoprazole (LPZ), pantoprazole (PPZ), and their respective stereoisomers following single and multiple intravenous doses in healthy Chinese subjects. MATERIALS AND METHODS: The dosage groups were set as follows: 30 mg single and multiple intravenous administrations of LPZ or R-LPZ, 40 mg single and multiple intravenous administrations of PPZ or S-PPZ. Subjects received an intravenous infusion of LPZ, R-LPZ, PPZ, or S-PPZ injection in sterile saline solution (100 mL/h, 60 minutes), respectively. The intragastric pH was sampled every second for 24 hours at baseline and for 24 hours after drug administration. The baseline-adjusted pharmacodynamic (PD) parameters include ΔMean (pH), ΔMedian (pH), ΔTpH≥3 (%), ΔTpH≥4 (%), ΔTpH≥6 (%), and ΔAUECph-tτ1-τ2. The PD parameters were evaluated in different time intervals (0 - 24 hours, 0 - 4 hours and 14 - 24 hours). RESULTS: After a single dose, the ΔTpH≥4 (%) of R-LPZ, LPZ, S-PPZ and PPZ was 56.6 ± 19.6, 53.1 ± 23.3, 35.6 ± 24.9 and 26.8 ± 30.2, respectively. The ΔTpH≥6 (%) was 50.7 ± 26.1, 41.4 ± 26.2, 25.4 ± 24.9 and 22.1 ± 27.6, respectively. The ΔAUECph-τ1-τ was 45,564 ± 16,107, 41,798 ± 16,153, 31,914 ± 17,304 and 20,744 ± 21,500, respectively. Statistically significant differences were found with R-LPZ vs. S-PPZ, R-LPZ vs. PPZ, LPZ vs. S-PPZ and LPZ vs. PPZ. The average TpH≥4 of R-LPZ, LPZ, S-PPZ, and PPZ was (47.2 ± 26.1) minutes, (49.6 ± 19.3) minutes, (56.1 ± 23.7) minutes, and (72.1 ± 27.3) minutes, respectively. Statistically significant differences were found with R-LPZ vs. PPZ (p = 0.009) and LPZ vs. PPZ (p = 0.019). After multiple doses, the ΔTpH≥4 (%) of R-LPZ, LPZ, S-PPZ, and PPZ was 71.7 ± 20.2, 63.5 ± 19.4, 59.5 ± 17.8 and 64.0 ± 22.4, respectively. The ΔTpH≥6 (%) was 64.0 ± 22.2, 52.0 ± 19.2, 49.6 ± 20.4 and 50.9 ± 23.8, respectively. The ΔAUECph-τ1-τ was 326,149 ± 94,839, 288,565 ± 93,279, 296,189 ± 83,412 and 300,960 ± 108,057, respectively. No statistically significant differences were found in baseline-adjusted PD parameters during all time periods after multiple doses. CONCLUSION: After a single dose, the mean gastric pH inhibition value of R-LPZ was the highest, followed by LPZ, then S-PPZ and PPZ. R-LPZ and LPZ provided significantly better pH control compared with PPZ and S-PPZ in healthy subjects. The onset time of R-LPZ was the fastest and R-LPZ can provide better acid inhibition during sleeping time. After multiple doses, the mean values in all PD parameters of R-LPZ were the highest, the values of LPZ, S-PPZ, and PPZ were similar. However, no significant difference was found in acid inhibition among these four drugs after multiple doses.


Assuntos
Antiulcerosos/farmacologia , Determinação da Acidez Gástrica , Lansoprazol/farmacologia , Pantoprazol/farmacologia , Voluntários Saudáveis , Humanos , Concentração de Íons de Hidrogênio , Estereoisomerismo
5.
J Vet Intern Med ; 33(5): 1988-1994, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31294879

RESUMO

BACKGROUND: Famotidine is sometimes administered as a continuous rate infusion (CRI) to treat gastrointestinal ulceration in critically ill dogs. However, clinical studies have not evaluated the efficacy of a famotidine CRI in dogs. HYPOTHESIS/OBJECTIVES: To evaluate the efficacy of famotidine at raising intragastric pH when it is administered as a CRI in dogs. We hypothesized that CRI treatment with famotidine would meet clinical goals for raising intragastric pH ≥3 and 4. ANIMALS: Nine healthy Beagle dogs. METHODS: Randomized 2-way crossover. All dogs received 1.0 mg/kg IV q12h famotidine or CRI famotidine at 1.0 mg/kg IV loading dose and 8.0 mg/kg/d for 3 consecutive days. Beginning on day 0 of treatment, intragastric pH monitoring was used to continuously record intragastric pH. Mean percentage times (MPTs) for which intragastric pH was ≥3 and ≥4 were compared between groups using analysis of variance. RESULTS: There was a statistically significant difference (P < .05) in MPT ≥3 and ≥4 between the CRI and IV q12h groups on all treatment days. On days 1, 2, and 3, the MPTs ± SD for which pH was ≥3 were 92.1 ± 8.5, 96.3 ± 6.2, and 90.0 ± 15.7 for the CRI treatment group and 49.3 ± 27.3, 42.2 ± 19.6, and 45.8 ± 10.1, respectively, for the twice-daily group. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest that a famotidine CRI, but not standard doses of famotidine, achieves the clinical goals established in people to promote healing of gastric tissue injury and offers an alternative to intravenous treatment with proton pump inhibitors in dogs.


Assuntos
Administração Intravenosa/veterinária , Antiulcerosos/farmacologia , Cães , Famotidina/farmacologia , Animais , Antiulcerosos/administração & dosagem , Estudos Cross-Over , Famotidina/administração & dosagem , Feminino , Determinação da Acidez Gástrica/veterinária , Masculino , Monitorização Fisiológica/veterinária , Estômago/efeitos dos fármacos
6.
Arch Pharm (Weinheim) ; 352(7): e1800339, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31231875

RESUMO

Ketoprofen belongs to one of the most common nonsteroidal anti-inflammatory drugs (NSAIDs) but its clinical usefulness has been restricted due to the high incidence of gastrointestinal complications. The release of reactive oxygen species (ROS) in NSAIDs therapy plays a major role in causing gastric complications. Antioxidants not only prevent gastric ulceration and lipid peroxidation but also preserve glutathione-type peroxidase (GPO) activity. Therefore, the present study investigates the utility of combining anti-inflammatory and antioxidant properties of two different compounds in a single molecule to form a series of 16 ketoprofen-antioxidant mutual codrugs. The free carboxylic group, which is believed to be one of the reasons for gastric toxicity of ketoprofen, was masked temporarily by simple and double esterification with alcoholic/phenolic-OH of natural antioxidants. In simple esterification, ketoprofen is directly linked to natural antioxidants (IIa-h) in the hope to obtain drugs free of gastric side effects. In an attempt to improve the in vivo lability, as well as gastric side effects, the double ester codrugs, that is, ketoprofen-antioxidant through the glycolic acid spacer (-CH2 COO; IIIa-h), have also been designed and synthesized. The synthesized codrugs were characterized by IR, 1 H NMR, 13 C NMR, mass spectroscopy and elemental analysis. The in vitro hydrolysis studies showed the lowest hydrolysis (highest stability) in acidic pH 1.2, whereas moderate hydrolysis was seen at pH 7.4 and significant hydrolysis in 80% human blood plasma, as indicated by their t1/2 . The pharmacological evaluation results indicate that these ketoprofen-antioxidant mutual codrugs showed the retention of anti-inflammatory and analgesic activity with a significant reduction in the ulcer index.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Antiulcerosos/farmacologia , Antioxidantes/farmacologia , Inflamação/tratamento farmacológico , Cetoprofeno/farmacologia , Analgésicos/síntese química , Analgésicos/química , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antiulcerosos/síntese química , Antiulcerosos/química , Antioxidantes/química , Compostos de Bifenilo/antagonistas & inibidores , Humanos , Hidrólise , Cetoprofeno/química , Cinética , Estrutura Molecular , Dor/tratamento farmacológico , Picratos/antagonistas & inibidores , Ratos , Úlcera Gástrica/tratamento farmacológico
7.
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
8.
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
9.
Zhonghua Nei Ke Za Zhi ; 58(5): 382-384, 2019 May 01.
Artigo em Chinês | MEDLINE | ID: mdl-31060148

RESUMO

The purpose of this study was to investigate the injury of aspirin and clopidogrel on small intestinal mucosa in rats and the protective effect of teprenone. The study found that aspirin and clopidogrel could cause intestinal mucosal injury in rats, which was even worse with dual drugs. The mechanism of mucosal injury included free radical injury induced by aspirin and decreased synthesis of vascular endothelial growth factor (VEGF) by clopidogrel. Teprenone may repair intestinal mucosa via boosting VEGF level.


Assuntos
Antiulcerosos/farmacologia , Aspirina/efeitos adversos , Clopidogrel/efeitos adversos , Diterpenos/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Animais , Antiulcerosos/uso terapêutico , Mucosa Intestinal/patologia , Ratos , Fator A de Crescimento do Endotélio Vascular
10.
Life Sci ; 229: 157-165, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31077719

RESUMO

AIM: This study investigates the insulin sensitizer effect of carbenoxolone (CBX) and potentially involved peripheral mechanisms. MAIN METHODS: Taking glucose transporter 4 (GLUT4) as a marker of glucose disposal, we investigated the CBX effects on whole-body insulin sensitivity and solute carrier 2a4 (Slc2a4)/GLUT4 expression in visceral (VAT) and subcutaneous (SAT) adipose tissues and soleus muscle of monosodium glutamate (MSG)-induced obese rats. Sterol regulatory element binding protein (SREBP1), an enhancer of Slc2a4 expression was analyzed through mRNA content and SREBP1-binding to Slc2a4 promoter. Finally, the small ubiquitin-modifier conjugating enzyme 9 (UBC9), whose low content indicates accelerated GLUT4 degradation was analyzed in soleus. KEY FINDINGS: Hypercorticosteronemia, hyperinsulinemia and low glucose decay rate in the insulin tolerance test of obese rats were restored by CBX (P < 0.05). Slc2a4/GLUT4 increased in SAT (P < 0.05) and decreased in VAT (P < 0.01) of obese rats. In soleus, obesity increased Slc2a4 but decreased GLUT4 (P < 0.01), possibly by accelerating GLUT4 degradation, as suggested by decreased UBC9 (P < 0.01). CBX restored both UBC9 and GLUT4 contents. SREBP1 did not participate in the Slc2a4 transcriptional regulation. SIGNIFICANCE: The insulin sensitizer effect of CBX involves the increase of GLUT4 expression in soleus, indicating an increased glucose disposal in skeletal muscle. This observation reinforces the skeletal muscle as the main site of insulin-induced glucose uptake and sheds new light on the metabolic effects of 11ßHSD1 inhibitors, since most of the studies so far have focused on its effects on liver and adipose tissues.


Assuntos
Carbenoxolona/farmacologia , Transportador de Glucose Tipo 4/metabolismo , Hiperinsulinismo/tratamento farmacológico , Resistência à Insulina , Músculo Esquelético/metabolismo , Obesidade/fisiopatologia , Enzimas de Conjugação de Ubiquitina/metabolismo , Animais , Antiulcerosos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 4/genética , Hiperinsulinismo/metabolismo , Hiperinsulinismo/patologia , Masculino , Músculo Esquelético/patologia , Ratos , Ratos Wistar , Enzimas de Conjugação de Ubiquitina/genética
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.
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
13.
Gen Physiol Biophys ; 38(2): 175-181, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30821252

RESUMO

In this study, we evaluated the anti-oxidant and anti-inflammatory effect of caftaric acid against ulcer produced by indomethacin in gastric mucosa. Female Sprague Dawley albino rats were divided into five groups: control (saline group, n = 8), negative control (indomethacin group, n = 8), positive control (omeprazole group, n = 8), low dose therapy (caftaric acid, n = 8), and high dose therapy (caftaric acid, n = 8). At the end of the experiment, all rats were sacrificed and gastric mucosa samples were removed for macroscopic and biochemical analysis. In our study, we detected that oxidant parameter values and cytokine levels increased in the negative control group, but total antioxidant status reduced, whereas, cytokine and oxidant parameter levels were significantly reduced due to low and high doses of caftaric acid administration. But another important point to note is that high dose caftaric acid therapy performed gastroprotective effect as omeprazole. In the macroscopic evaluation, there were reductions in ulcer sizes with a low and high dose of caftaric acid administration in contrast to the negative control group. As a result of our study, caftaric acid showed anti-oxidant and anti-inflammatory effects in indomethacin-induced gastric ulcer in rats.


Assuntos
Antiulcerosos , Antioxidantes , Fenóis , Úlcera Gástrica , Animais , Antiulcerosos/farmacologia , Feminino , Indometacina/farmacologia , Oxidantes , Fenóis/farmacologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Úlcera Gástrica/tratamento farmacológico
14.
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
15.
J Vet Intern Med ; 33(2): 544-550, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30746763

RESUMO

BACKGROUND: Famotidine is commonly administered to cats. Prolonged famotidine administration results in decreased efficacy in humans, dogs, and cows, but the long-term effects in cats are unknown. OBJECTIVES: To compare the effect of 2 oral administration frequencies of famotidine, twice daily (Group 1) and twice daily every second day (Group 2), on intragastric pH and serum gastrin concentrations in cats. We hypothesized a diminished effect on intragastric pH would be observed over time in Group 1 but not Group 2. ANIMALS: Sixteen healthy cats. METHODS: Randomized, 2-factor repeated measures crossover design. Cats received 0.5-1.24 mg/kg (median, 0.87 mg/kg) famotidine twice daily or twice daily every second day for 14 consecutive days. Intragastric pH monitoring was used to record intragastric pH on treatment days 1-3 and 11-13. Mean pH and mean percentage time (MPT) intragastric pH was ≥3 and 4 were compared between and within treatment groups by analysis of variance. RESULTS: Significant treatment group by time interactions were observed for mean intragastric pH, MPT intragastric pH ≥3 and 4 (P = .009, P = .02, P = .005, respectively). Interaction post hoc tests identified significant decreases in mean intragastric pH (P = .001), MPT ≥3 (P = .001), and MPT ≥4 (P = .001) on day 13 compared to day 1 in Group 1 but not in Group 2. CONCLUSIONS AND CLINICAL IMPORTANCE: Oral famotidine administration results in a diminished effect on intragastric pH in healthy cats when given twice daily every day.


Assuntos
Antiulcerosos/farmacologia , Gatos/metabolismo , Famotidina/farmacologia , Ácido Gástrico/metabolismo , Administração Oral , Animais , Antiulcerosos/administração & dosagem , Estudos Cross-Over , Esquema de Medicação/veterinária , Famotidina/administração & dosagem , Feminino , Determinação da Acidez Gástrica/veterinária , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Masculino , Distribuição Aleatória
16.
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
17.
BMC Pharmacol Toxicol ; 20(1): 13, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30770761

RESUMO

BACKGROUND: Basic function of bromine in body is to activate pepsin production in gastritis with low acidity. The present study encompasses a broad in vivo study to evaluate gastroprotective activity of a novel dibromo substituted Schiff base complex against Sprague Dawley (SD) rats. METHODS: 2, 2'-[1, 2-cyclohexanediylbis (nitriloethylidyne)]bis(4-bromophenol) (CNBP) is synthesized via a Schiff base reaction, using the related ketone and diamine as the starting materials. SD rats are divided as normal, ulcer control (5 ml/kg of 10% Tween 20), testing (10 and 20 mg/kg of CNBP) and reference groups (omeprazole 20 mg/kg). Except for the normal group, the rest of the groups are induced gastric ulcer by ethanol 1 h after the pre-treatment. Ulcer area, gastric wall mucus, and acidity of gastric content of the animal stomachs are measured after euthanization. Antioxidant activity of the compound is tested by Ferric reducing antioxidant power (FRAP) test and safety of the compound is identified through acute toxicity by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Moreover, activities of superoxide dismutase (SOD), catalase (CAT), levels of prostaglandins E2 (PGE2) and also malondialdehyde (MDA) are determined. RESULTS: Antioxidant activity of CNBP was approved via FRAP assay. Vast shallow hemorrhagic injury of gastric glandular mucosa was observed in the ulcer group compared to the CNBP-treated animals. Histological evaluations confirmed stomach epithelial defense effect of CNBP with drastic decrease of gastric ulceration, edema and leucocytes penetration of submucosal stratum. Immunostaining exhibited over-expression in HSP70 protein in CNBP-treated groups compared to that of the ulcer group. Also, gastric protein analysis showed low levels of MDA, PGE2 and high activity of SOD and CAT. CONCLUSIONS: CNBP with noticeable antioxidant property showed gastroprotective activity in the testing rodents via alteration of HSP70 protein expression. Also, antioxidant enzyme activities which were changed after treatment with CNBP in the animals could be elucidated as its gastroprotective properties.


Assuntos
Antiulcerosos/uso terapêutico , Antioxidantes/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Animais , Antiulcerosos/farmacologia , Antioxidantes/farmacologia , Catalase/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dinoprostona/metabolismo , Etanol , Feminino , Proteínas de Choque Térmico HSP70/metabolismo , Ratos Sprague-Dawley , Estômago/efeitos dos fármacos , Estômago/patologia , Estômago/fisiologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Superóxido Dismutase/metabolismo
18.
J Ethnopharmacol ; 235: 268-278, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-30763697

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Eugenia punicifolia (Kunth) DC. (Myrtaceae), an Amazonian medicinal plant known as "pedra-ume-caá," is popularly used as a natural remedy for inflammation, wounds, infections, diabetes, fever, and flu. Its anti-inflammatory, antinociceptive, and gastroprotective effects have already been characterized. We evaluated the gastric healing effect of the hydroalcoholic extract of the leaves of E. punicifolia (HEEP) in male and female Wistar rats against nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol. MATERIALS AND METHODS: The healing effect of HEEP on the gastric mucosa of adult male and female Wistar rats was measured after the chronic application of aggressive factors such as NSAIDs or 80% ethanol. Male, and intact and ovariectomized (OVZ) female rats were treated with HEEP for two days (NSAIDs) or one, two, four, and six days (80% ethanol). The stomachs were analyzed macroscopically for ulcerative lesions (mm2), and the healing process was measured using biochemical analysis with anti-inflammatory and antioxidant parameters. RESULTS: Macroscopic evaluation of the gastric mucosa showed that gastric lesions induced by NSAIDs were significantly healed (66%) and pro-inflammatory interleukin 5 cytokine level was decreased after two-day oral treatment with HEEP compared with those in the negative control group (p < 0.05). However, the gastric lesions induced by NSAIDs did not heal in HEEP-treated female rats (p > 0.05). In addition, four-day treatment with HEEP significantly healed the gastric lesions induced by ethanol in male and female rats (63% and 78%, respectively) compared to those of the negative control group (p < 0.05). However, the OVZ group required six days of HEEP treatment to heal gastric ulcers (67% compared to the control group). HEEP exerts the healing effect against ethanol by significantly reducing neutrophil infiltration into the gastric mucosa by decreasing myeloperoxidase activity in male and OVZ rats after four and six days of treatment, respectively (p < 0.05). Four-day treatment with HEEP also increased the level of a non-enzymatic antioxidant, reduced glutathione in intact females compared to that of the negative control group (p < 0.05). CONCLUSION: These findings indicated that HEEP was effective in promoting the healing of gastric ulcers induced by NSAIDs or ethanol. The gastric healing effects of this extract could be affected by female sex hormone interference; in future, comprehensive studies should be performed by considering sex differences.


Assuntos
Antiulcerosos/farmacologia , Eugenia/química , Extratos Vegetais/farmacologia , Úlcera Gástrica/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/toxicidade , Antiulcerosos/isolamento & purificação , Antioxidantes/metabolismo , Modelos Animais de Doenças , Etanol/toxicidade , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Masculino , Folhas de Planta , Ratos , Ratos Wistar , Fatores Sexuais , Úlcera Gástrica/patologia , Cicatrização/efeitos dos fármacos
19.
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
20.
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
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA