RESUMEN
Activation of 5' adenosine monophosphate-activated protein kinase (AMPK) stimulates production of the gaseous mediators nitric oxide (NO) and carbon monoxide (CO), which are involved in mucosal defense and gastroprotection. As AMPK itself has gastroprotective effects against several gastric ulcer etiologies, in the present study, we aimed to elucidate whether AMPK may also prevent ethanol-induced injury and play a key role in the associated gastroprotection mediated by hydrogen sulfide (H2S), NO, and CO. Mice were pretreated with AICAR (20â¯mg/kg, an AMPK activator) alone or with 50% ethanol. Other groups were pretreated with respective gaseous mediator inhibitors PAG, l-NAME, or ZnPP IX 30â¯min prior to AICAR, or with gaseous mediator donors NaHS, Lawesson's reagent and l-cysteine (H2S), SNP, l-Arginine (NO), Hemin, or CORM-2 (CO) 30â¯min prior to ethanol with or without compound C (10â¯mg/kg, a non-selective AMPK inhibitor). H2S, nitrate/nitrite (NO3-/NO2-), bilirubin levels, GSH and MDA concentration were evaluated in the gastric mucosa. The gastric mucosa was also collected for histopathological analysis and AMPK expression assessment by immunohistochemistry. Pretreatment with AICAR attenuated the ethanol-induced injury and increased H2S and bilirubin levels but not NO3-/NO2- levels in the gastric mucosa. In addition, inhibition of H2S, NO, or CO synthesis exacerbated the ethanol-induced gastric damage and inhibited the gastroprotection by AICAR. Pretreatment with compound C reversed the gastroprotective effect of NaHS, Lawesson's reagent, l-cysteine, SNP, l-Arginine, CORM-2, or Hemin. Compound C also reversed the effect of NaHS on H2S production, SNP on NO3-/NO2- levels, and Hemin on bilirubin levels. Immunohistochemistry revealed that AMPK is present at basal levels mainly in the gastric mucosa cells, and was increased by pretreatment with NaHS, SNP, and CORM-2. In conclusion, our findings indicate that AMPK activation exerts gastroprotection against ethanol-induced gastric damage and mutually interacts with H2S, NO, or CO to facilitate this process.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Monóxido de Carbono/metabolismo , Gasotransmisores/metabolismo , Sulfuro de Hidrógeno/metabolismo , Óxido Nítrico/metabolismo , Gastropatías/prevención & control , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacología , Animales , Bilirrubina/metabolismo , Activación Enzimática , Activadores de Enzimas/farmacología , Etanol , Femenino , Mucosa Gástrica/patología , Masculino , Ratones , Ribonucleótidos/farmacología , Gastropatías/inducido químicamenteRESUMEN
A sulfated polysaccharide (SFP) fraction from the marine alga Solieria filiformis was extracted and submitted to microanalysis, molar mass estimation and spectroscopic analysis. We evaluated its gastroprotective potential in vivo in an ethanol-induced gastric damage model and its in vitro antioxidant properties (DPPH, chelating ferrous ability and total antioxidant capacity). Its chemical composition revealed to be essentially an iota-carrageenan with a molar mass of 210.9kDa and high degree of substitution for sulfate groups (1.08). In vivo, SFP significantly (P<0.05) reduced, in a dose dependent manner, the ethanol-induced gastric damage. SFP prevents glutathione consume and increase of malondialdehyde and hemoglobin levels. SFP presented an IC50 of 1.77mg/mL in scavenging DPPH. The chelating ferrous ability was 38.98%, and the total antioxidant capacity was 2.01mg/mL. Thus, SFP prevents the development of ethanol-induced gastric damage by reducing oxidative stress in vivo and possesses relevant antioxidant activity in vitro.
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Antioxidantes , Estrés Oxidativo/efectos de los fármacos , Polisacáridos , Rhodophyta/química , Gastropatías/prevención & control , Animales , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Etanol/toxicidad , Ratones , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología , Gastropatías/inducido químicamenteRESUMEN
INTRODUCTION AND AIMS: The chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause complications in the gastrointestinal tract. The use of proton pump inhibitors (PPIs) is recommended in high-risk patients to prevent them. OBJECTIVE: The aim of this article was to evaluate the gastroprotection measures taken in persons with chronic NSAID use. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted. The clinical records were reviewed of patients seen as outpatients at the Rheumatology Department over a 4-month period, choosing those with chronic NSAID use, and intentionally looking for gastroprotection measures according to the recommendations published by the American College of Gastroenterology. RESULTS: A total of 417 patients (347 women; mean age: 48.12±14.2 years) were included. The most frequent diagnosis was rheumatoid arthritis (65%). Nine patients (2.1%) had a history of peptic ulcer, 48 (11.5%) patients were 65 years of age or older, 26 (6.2%) patients took NSAIDs and aspirin, and 130 (31.2%) took NSAIDs with steroids. Tests for Helicobacter pylori infection were done in just 53 cases, and there were positive results in only 9 (16%). Some risk for gastrointestinal toxicity was established in 211 cases and only 65 (30.8%) received gastroprotection. In contrast, 31 (15%) patients received gastroprotection when there was no indication for it. CONCLUSION: Prophylaxis with PPIs in chronic NSAID users was inadequately employed. It was not prescribed in the majority of patients (69.2%) and it was used with no justification in others (15%).
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Guías de Práctica Clínica como Asunto , Inhibidores de la Bomba de Protones/uso terapéutico , Gastropatías/inducido químicamente , Gastropatías/prevención & control , Adulto , Anciano , Estudios Transversales , Utilización de Medicamentos , Femenino , Humanos , Masculino , México , Persona de Mediana EdadRESUMEN
BACKGROUND: Rebamipide is a gastroprotective agent with promising results against gastric damage induced by non-steroidal anti-inflammatory drugs. The present study evaluated if rebamipide protects against naproxen-induced gastric damage in healthy volunteers. Changes in gastric PGE2 tissue concentration were also evaluated. METHODS: After a preliminary endoscopy to rule out previous gastric macroscopic damage, twenty-four healthy volunteers of both sexes were divided into 2 groups. One group received sodium naproxen 550 mg b.i.d. plus placebo for 7 days, while the other group received sodium naproxen 550 mg b.i.d. plus rebamipide 100 mg b.i.d. At the end of treatment, a new endoscopy was performed. Gastric macroscopic damage was evaluated by the Cryer score and by the modified Lanza score. The primary outcome measure of the trial was the macroscopic damage observed in each treatment group at the end of treatment. Biopsies were collected at both endoscopies for PGE2 quantification and histopathological analysis (secondary outcomes). Tissue PGE2 was quantified by ELISA. The randomization sequence was generated using 3 blocks of 8 subjects each. Volunteers and endoscopists were blind to whether they were receiving rebamipide or placebo. RESULTS: All recruited volunteers completed the trial. Sodium naproxen induced gastric damage in both groups. At the end of the study, median Cryer score was 4 in both groups (Difference = 0; 95%CI = -1 to 0; p = 0.728). In the placebo group, the mean tissue PGE2 concentration was 1005 ± 129 pg/mL before treatment and 241 ± 41 pg/mL after treatment (p < 0.001). In the rebamipide group, the mean tissue PGE2 concentration was 999 ± 109 pg/mL before treatment, and 168 ± 13 pg/mL after treatment (p < 0.001). There was no difference in mean tissue PGE2 between the two groups (difference = 5; 95%CI from -334.870 to 345.650; p = 0.975). No significant change was observed at the histopathological evaluation, despite the evident macroscopic damage induced by naproxen. CONCLUSION: Rebamipide does not protect against naproxen-induced gastric damage in healthy volunteers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02632812 . Registered 14 December 2015.
Asunto(s)
Alanina/análogos & derivados , Antiinflamatorios no Esteroideos/efectos adversos , Fármacos Gastrointestinales/uso terapéutico , Naproxeno/efectos adversos , Quinolonas/uso terapéutico , Gastropatías/inducido químicamente , Gastropatías/prevención & control , Adolescente , Adulto , Alanina/uso terapéutico , Dinoprostona/análisis , Método Doble Ciego , Femenino , Mucosa Gástrica/patología , Humanos , Masculino , Persona de Mediana Edad , Gastropatías/patología , Adulto JovenRESUMEN
BACKGROUND: Biological control of gastrointestinal nematodes of ruminants by use of nematophagous fungi would become part of any livestock parasite integral control system. Identifying autochthonous species that could then be selected for mass production is an important phase in the practical use of biological control. AIMS: To search for nematophagous fungi with potential use as biological control agents against gastrointestinal nematodes in Argentina. METHODS: Decomposing cattle faeces sampled in different locations were incubated in water agar 2% with Panagrellus sp. The developed nematophagous fungi were transferred to new water agar 2% plates and then to corn meal agar plates in order to carry out their identification. Fungal diversity and richness were also assessed. RESULTS: Seventeen species from nine genera of nematophagous fungi were found. Twelve species were nematode-trapping fungi and three species plus two fungi identified to genus level corresponded to endoparasitic fungi. Arthrobotrys conoides, Arthrobotrys oligospora, Duddingtonia flagrans, Monacrosporium doedycoides, Arthrobotrys robusta and Drechmeria coniospora were the most frequently isolated species overall in the whole study (6.6%, 5.7%, 5.7%, 5.7%, 4.7% and 4.7%, respectively) although other species were more frequently recorded at local levels such as Arthrobotrys pyriformis (18.8%). Only A. conoides has been previously isolated from ruminant faecal samples in Argentina. Five nematode-trapping fungal species are mentioned for the first time in the Americas CONCLUSIONS: D. flagrans and A. conoides, both identified in the present study, are among the most promising ones as biological control agents against gastrointestinal nematodes of ruminants.
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Heces/microbiología , Hongos/aislamiento & purificación , Animales , Argentina/epidemiología , Bovinos , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/parasitología , Enfermedades de los Bovinos/prevención & control , Heces/parasitología , Hongos/fisiología , Helmintiasis Animal/epidemiología , Helmintiasis Animal/parasitología , Helmintiasis Animal/prevención & control , Parasitosis Intestinales/epidemiología , Parasitosis Intestinales/parasitología , Parasitosis Intestinales/prevención & control , Parasitosis Intestinales/veterinaria , Nematodos , Control Biológico de Vectores , Especificidad de la Especie , Gastropatías/epidemiología , Gastropatías/parasitología , Gastropatías/prevención & control , Gastropatías/veterinariaRESUMEN
Objetivos. Determinar el efecto gastroprotector y antisecretor del extracto etanólico de las hojas de matico (Piper aduncum) en modelos animales. Materiales y métodos. Para la evaluación del efecto gastroprotector se utilizó 220 ratones de la cepa Balb C57, los cuales fueron aleatorizados en 22 grupos de diez animales, a los cuales se les indujo la formación de úlceras gástricas con indometacina, la gastroprotección se determinó a través de tres aspectos: inflamación, número de bandas hemorrágicas y número de úlceras. Para evaluar el efecto antisecretor se utilizó 64 ratas albinas machos Holtzman, los cuales fueron aleatorizados en ocho grupos de ocho animales, un control y siete grupos de tratamiento con un nivel de dosis de los extractos y dos niveles de dosis en los fitofármacos; la antisecreción se realizó con el ensayo de ligazón pilórica. Resultados. Para la gastroprotección, los extractos de diclorometano, cloroformo, hexano y metanol, lograron una disminución de la inflamación de más del 66% (p<0,05); el extracto etanólico presenta una actividad de 100% para disminuir el número de bandas hemorrágicas (p<0,05); el extracto clorofórmico presenta una actividad antiulcerosa de 75% (p<0,05). Respecto a la antisecreción, el fitofármaco en cápsulas conteniendo el extracto etanólico logró un 72% de reducción del volumen de la secreción gástrica (p<0,01) y un incremento del pH en 104,3% (p<0,01). Conclusiones. En condiciones experimentales los extractos etanólico, sus fracciones y su fitofármaco son gastroprotectores en ratones y antisecretores en ratas.
Objectives. To determine the gastroprotective and antisecretory effect of ethanol extract from matico leaves (Piper aduncum) in animal models. Materials and methods. To evaluate the gastroprotective effect, 220 mice of the Balb C57 strain were used. They were randomized in 22 groups of ten animals each, in which the formation of gastric ulcers was induced with indomethacin. Gastroprotection was determined by evaluating three aspects: inflammation, number of hemorrhagic shocks and number of ulcers. To evaluate the antisecretory effect, 64 white male Holtzman rats were used, which were randomized in eight groups of eight animals, one control and seven groups of treatment with one extract dose level and two phytochemical dose levels. Antisecretion was obtained through the pylorus ligation. Results. Regarding gastroprotection, dichloromethane, chloroform, hexane and methanol extracts decreased inflammation to over 66% (p<0,05). The ethanolic extract shows 100% activity in reducing the number of hemorrhagic bands (p<0,05). The chloroform extract shows antiulcer activity at 75% (p<0,05). In terms of antisecretion, the phytochemical in capsules containing the ethanolic extract achieved 72% reduction of the gastric secretion volume (p<0,01) and 104,3% (p<0,01) PH increase. Conclusions. In experimental conditions, ethanolic extracts, their fractions and phytochemicals have a gastroprotective effect in mice and antisecretory effect in rats.
Asunto(s)
Animales , Ratones , Ratas , Jugo Gástrico/efectos de los fármacos , Jugo Gástrico , Fitoterapia , Piper , Extractos Vegetales/uso terapéutico , Hojas de la Planta , Gastropatías/prevención & control , Etanol , Ratones Endogámicos BALB CRESUMEN
OBJECTIVES: To determine the gastroprotective and antisecretory effect of ethanol extract from matico leaves (Piper aduncum) in animal models. MATERIALS AND METHODS: To evaluate the gastroprotective effect, 220 mice of the Balb C57 strain were used. They were randomized in 22 groups of ten animals each, in which the formation of gastric ulcers was induced with indomethacin. Gastroprotection was determined by evaluating three aspects: inflammation, number of hemorrhagic shocks and number of ulcers. To evaluate the antisecretory effect, 64 white male Holtzman rats were used, which were randomized in eight groups of eight animals, one control and seven groups of treatment with one extract dose level and two phytochemical dose levels. Antisecretion was obtained through the pylorus ligation. RESULTS: Regarding gastroprotection, dichloromethane, chloroform, hexane and methanol extracts decreased inflammation to over 66% (p<0,05). The ethanolic extract shows 100% activity in reducing the number of hemorrhagic bands (p<0,05). The chloroform extract shows antiulcer activity at 75% (p<0,05). In terms of antisecretion, the phytochemical in capsules containing the ethanolic extract achieved 72% reduction of the gastric secretion volume (p<0,01) and 104,3% (p<0,01) PH increase. CONCLUSIONS: In experimental conditions, ethanolic extracts, their fractions and phytochemicals have a gastroprotective effect in mice and antisecretory effect in rats.
Asunto(s)
Jugo Gástrico/efectos de los fármacos , Jugo Gástrico/metabolismo , Fitoterapia , Piper , Extractos Vegetales/uso terapéutico , Hojas de la Planta , Gastropatías/prevención & control , Animales , Etanol , Ratones , Ratones Endogámicos BALB C , RatasRESUMEN
OBJECTIVE: The aim of this study was to describe the results of endoscopic secondary prophylaxis, alone or in combination with propranolol, used to prevent upper gastrointestinal bleeding (UGIB) in children and adolescents with esophageal varices. METHODS: This observational study followed 43 patients younger than 18 years who received secondary prophylaxis between August 2001 and December 2009. Sclerotherapy and/or band ligation were performed, and propranolol was used when no contraindications were present. The rebleeding rate, number of endoscopic sessions required for variceal eradication, rate of varix recurrence, the occurrence of varices at the gastric fundus, and the occurrence of portal hypertensive gastropathy were evaluated. RESULTS: Endoscopic prophylaxis in combination with propranolol was performed in 25 patients (58.1%) and endoscopic prophylaxis alone was performed in 18 patients (41.9%). Esophageal varices were eradicated in all of the patients after a median of 3 sessions. Varices recurred in 22 patients (51.2%). Rebleeding occurred in 13 patients (30.2%). Fundal varices and portal hypertensive gastropathy developed in 31% and 61.9% of patients, respectively. No deaths related to the endoscopic procedure or UGIB occurred. No statistically significant differences in any of the studied variables were observed when comparing endoscopic prophylaxis with propranolol and endoscopic prophylaxis alone. CONCLUSIONS: No significant differences were observed between sclerotherapy and band ligation. Secondary prophylaxis was effective in eradicating esophageal varices. The use of propranolol did not affect the results of the endoscopic prophylaxis. Furthermore, randomized studies will be necessary to assess the best form of prevention during childhood.
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Antagonistas Adrenérgicos beta/uso terapéutico , Endoscopía Gastrointestinal , Várices Esofágicas y Gástricas/terapia , Unión Esofagogástrica/cirugía , Esófago , Propranolol/uso terapéutico , Escleroterapia , Adolescente , Niño , Preescolar , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/cirugía , Esófago/cirugía , Femenino , Fundus Gástrico , Hemorragia/epidemiología , Hemorragia/etiología , Hemorragia/prevención & control , Humanos , Hipertensión Portal/epidemiología , Hipertensión Portal/etiología , Hipertensión Portal/prevención & control , Ligadura , Masculino , Prevalencia , Recurrencia , Gastropatías/epidemiología , Gastropatías/etiología , Gastropatías/prevención & control , Resultado del TratamientoRESUMEN
The objective of this study was to evaluate effects of feeding monensin (MON) or a multivalent polyclonal antibody preparation (PAP) against several rumen microorganisms on feedlot performance, carcass characteristics, blood gas profile, and rumenitis of Bos indicus biotype (BT) yearling bulls. The study was designed as a completely randomized design with a 3 × 2 factorial arrangement, replicated 4 times, in which 32 yearling bulls of each of 3 BT evaluated (3-way-cross, TC; Canchim, CC; and Nellore, NE) were fed diets containing either MON at 300 mg·d(-1) or PAP at 10 mL·d(-1) across 3 different periods. No significant (P > 0.10) feed additive (FA) main effects were observed for any of the feedlot performance variables and carcass characteristics with the exception of dressing percentage. Yearling bulls receiving PAP had a decreased (P = 0.047) dressing percentage when compared with yearling bulls receiving MON. Significant (P < 0.05) BT main effects were observed for all feedlot performance variables and carcass characteristics with the exception of kidney-pelvic fat expressed in kilograms (P = 0.49) and LM lipids content (P = 0.45). Crossbred yearling bulls (TC and CC) had greater (P < 0.001) ADG, DMI in kilograms, DMI as % of BW, and improved (P = 0.001) G:F when compared with NE yearling bulls. A tendency (P = 0.072) for a FA main effect was observed for rumenitis scores, in which yearling bulls receiving PAP had lesser rumenitis scores than those receiving MON. When the data were disposed as frequency percentage, 55.6% and 45.7% of the rumens from yearling bulls fed PAP and MON were scored between 0 and 1, respectively (0 = no lesions, 10 = severe lesions). Likewise, a significant BT main effect was observed (P = 0.008), where NE yearling bulls had greater rumenitis scores than those of crossbred yearling bulls (TC and CC). No significant FA main effects were observed (P > 0.10) for any of the fatty acids measured in the subcutaneous adipose tissue, with the exception that yearling bulls receiving MON had greater (P < 0.05) concentrations of palmitic acid (16:0), margaric acid (17:0), docosapentaenoic acid (22:5), and docosahexaenoic acid (22:6) than those yearling bulls receiving PAP. Feeding PAP tended to decrease incidence of rumen lesions and led to similar feedlot performance compared with feeding MON. Thus, PAP is a new technology that presents a possible alternative for ionophores.
Asunto(s)
Anticuerpos Antibacterianos/farmacología , Composición Corporal/efectos de los fármacos , Enfermedades de los Bovinos/prevención & control , Dieta/veterinaria , Rumen/patología , Gastropatías/veterinaria , Tejido Adiposo/química , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Anticuerpos Antibacterianos/administración & dosificación , Bovinos , Ácidos Grasos/química , Ácidos Grasos/metabolismo , Fermentación , Absceso Hepático/patología , Absceso Hepático/veterinaria , Masculino , Monensina/farmacología , Gastropatías/prevención & controlRESUMEN
Starting from the diterpene (4S,9R,10R) methyl 18-carboxy-labda-8,13(E)-dien-15-oate (PMD) and its 8(9)-en isomer [PMD 8(9)-en], 11 amides were prepared and assessed for a gastroprotective effect in the ethanol/HCl-induced gastric lesions model in mice. Basal cytotoxicity of the compounds was determined on the following human cell lines: normal lung fibroblasts (MRC-5), gastric epithelial adenocarcinoma (AGS), and hepatocellular carcinoma (Hep G2). All compounds are described for the first time. At the single oral dose of 0.1 mg/kg, compounds 1, 10, and 11 presented a strong gastroprotective effect, at least comparable with that of the reference compound lansoprazole at 1 mg/kg, reducing gastric lesions by 76.7, 67.7, and 77.2 %, respectively. The leucyl amide methyl ester 3, tryptophanyl amide methyl ester 5, and benzyl amide 6 of PMD presented a selective basal cytotoxicity on Hep G2 cells with IC50 values of 136.8, 105.3, and 94.2 µM, respectively, while the IC50 values towards AGS cells were 439.5, 928.0, and 937.3 µM, respectively. The three compounds did not affect fibroblast viability with IC50 values > 1000 µM. Compounds 7, 8, 10, and 11 showed no toxic effect against the three selected cell lines.
Asunto(s)
Amidas/farmacología , Diterpenos/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Gastropatías/prevención & control , Amidas/química , Animales , Antineoplásicos Fitogénicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Línea Celular Tumoral , Modelos Animales de Enfermedad , Diterpenos/química , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Humanos , Pulmón/citología , Pulmón/efectos de los fármacos , Masculino , Ratones , Extractos Vegetales/farmacología , Polyalthia/química , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
The aim of the present study was to investigate the gastroprotective activity of a sulfated-polysaccharide (PLS) fraction extracted from the marine red algae Gracilaria caudata and the mechanism underlying the gastroprotective activity. Male Swiss mice were treated with PLS (3, 10, 30 and 90 mg·kg(-1), p.o.), and after 30 min, they were administered 50% ethanol (0.5 mL/25 g(-1), p.o.). One hour later, gastric damage was measured using a planimeter. Samples of the stomach tissue were also obtained for histopathological assessment and for assays of glutathione (GSH) and malondialdehyde (MDA). Other groups were pretreated with l-NAME (10 mg·kg(-1), i.p.), dl-propargylglycine (PAG, 50 mg·kg(-1), p.o.) or glibenclamide (5 mg·kg(-1), i.p.). After 1 h, PLS (30 mg·kg(-1), p.o.) was administered. After 30 min, ethanol 50% was administered (0.5 mL/25 g(-1), p.o.), followed by sacrifice after 60 min. PLS prevented-ethanol-induced macroscopic and microscopic gastric injury in a dose-dependent manner. However, treatment with l-NAME or glibenclamide reversed this gastroprotective effect. Administration of propargylglycine did not influence the effect of PLS. Our results suggest that PLS has a protective effect against ethanol-induced gastric damage in mice via activation of the NO/K(ATP) pathway.
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Etanol/toxicidad , Gracilaria/química , Polisacáridos/farmacología , Gastropatías/prevención & control , Alquinos/farmacología , Animales , Relación Dosis-Respuesta a Droga , Glutatión/metabolismo , Gliburida/farmacología , Glicina/análogos & derivados , Glicina/farmacología , Canales KATP/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/metabolismo , Polisacáridos/administración & dosificación , Polisacáridos/aislamiento & purificación , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/aislamiento & purificación , Sustancias Protectoras/farmacología , Gastropatías/inducido químicamenteRESUMEN
BACKGROUND AND RATIONALE: Portal hypertension (PHI) is a clinical syndrome characterized by increases of the blood flow and/or of the vascular resistance in the portal system. A direct consequence of PHI can appearance different lesions on the gastric mucosa and submucosa, cumulatively termed portal hypertensive gastropathy (PHG). AIMS: To investigate the effects of glutamine on oxidative stress in an experimental model of PHG induced by partial portal vein ligation (PPVL). MATERIAL AND METHODS: Portal pressure, transaminase and alkaline phosphatase activity were quantified. Gastric tissue damage was assessed by histological analysis. Oxidative stress was measured by quantification of cytosolic concentration of thiobarbituric acid reactive substances (TBARS), hydroperoxide-initiated chemiluminescence (QL), and nitric oxide (NO) production. Moreover, activities of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were analyzed. RESULTS: Transaminase and alkaline phosphatase activities were not significantly modified by PPVL, indicating absence of liver injury. Histological analysis of gastric sections showed a lost of normal architecture, with edema and vasodilatation. TBARS, QL, and NO production were significantly increased in PPVL animals. A reduction of SOD activity was found. Glutamine administration markedly alleviated histological abnormalities and oxidative stress, normalized SOD activity, and blocked NO overproduction. CONCLUSIONS: Our results confirm that the use of molecules with antioxidant capacity can provide protection of the gastric tissue in portal hypertension. Glutamine treatment can be useful to reduce the oxidative damage induced by PHI on gastric tissue.
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Antioxidantes/farmacología , Glutamina/farmacología , Hipertensión Portal/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Gastropatías/prevención & control , Estómago/efectos de los fármacos , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Animales , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Biomarcadores/metabolismo , Catalasa/metabolismo , Modelos Animales de Enfermedad , Mucosa Gástrica/metabolismo , Glutatión Peroxidasa/metabolismo , Hipertensión Portal/complicaciones , Hipertensión Portal/metabolismo , Ligadura , Peroxidación de Lípido/efectos de los fármacos , Masculino , Óxido Nítrico/metabolismo , Vena Porta/cirugía , Ratas , Ratas Wistar , Estómago/patología , Gastropatías/etiología , Gastropatías/metabolismo , Gastropatías/patología , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
BACKGROUND: Amifostine has been widely tested as a cytoprotective agent against a number of aggressors in different organs. Recently, a gastroprotective effect was observed for this drug in a model of indomethacin-induced gastric injury. Our objective was to investigate the effect of amifostine on ethanol-induced gastric injury and the role played in this mechanism by afferent sensory neurons, non-protein sulfhydryl groups, nitric oxide, ATP-sensitive potassium channels, and cyclooxygenase-2. METHODS: Rats were treated with amifostine (22.5, 45, 90, or 180 mg/kg, PO or SC). After 30 min, the rats received absolute ethanol (5 ml kg(-1), PO). One hour later, gastric damage was quantified with a planimeter. Samples from the stomach were also taken for histopathological assessment and for assays of non-protein sulfhydryl groups. The other groups were pretreated with L-NAME (10 mg kg(-1), IP), glibenclamide (10 mg kg(-1), PO), or celecoxib (10 mg kg(-1), PO). After 30 min, the animals were given amifostine (90 mg kg(-1), PO or SC), followed 30 min later by gavage with absolute ethanol (5 ml kg(-1)). Other rats were desensitized with capsaicin (125 mg kg(-1), SC) 8 days prior to amifostine treatment. RESULTS: Amifostine administration PO and SC significantly and dose-dependently reduced ethanol-induced macroscopic and microscopic gastric damage by restoring glutathione levels in the stomach mucosa. Amifostine-promoted gastroprotection against ethanol-induced stomach injury was reversed by pretreatment with neurotoxic doses of capsaicin, but not by L-NAME, glibenclamide, or celecoxib. CONCLUSIONS: Amifostine protects against ethanol-induced gastric injury by increasing glutathione levels and stimulating the afferent sensory neurons in the stomach.
Asunto(s)
Amifostina/farmacología , Capsaicina/farmacología , Etanol/toxicidad , Neuronas Aferentes/efectos de los fármacos , Gastropatías/inducido químicamente , Compuestos de Sulfhidrilo/metabolismo , Amifostina/administración & dosificación , Animales , Relación Dosis-Respuesta a Droga , Vías de Administración de Medicamentos , Mucosa Gástrica/efectos de los fármacos , Masculino , Protectores contra Radiación/farmacología , Ratas , Ratas Wistar , Gastropatías/prevención & controlRESUMEN
Free radicals production and oxidative stress play a central role in injuries caused by ethanol (EtOH) on gastric mucosal. Thus, strategies to counteract EtOH toxicity are highly desirable. This study was aimed at evaluating whether Vernonia cognata extract would reduce EtOH effects in rats. Rats received Vernonia cognata extract (0, 1 and 2 g/kg bw, by gavage) 1 hour after EtOH had been administered (0 or 70%, 0.5 mL/100 g bw, by gavage) and were killed 1 hour after Vernonia cognata extract administration. The stomach was removed for macroscopic and histopathological evaluation, as well as, oxidative stress markers such as lipoperoxidation (LPO) and non-protein thiol groups (NPSH) levels and catalase (CAT) activity. EtOH acute exposure increased LPO and decreased NPSH levels and CAT activity along with macroscopic and microscopic lesions in gastric tissue, confirming the involvement of oxidative stress in EtOH toxicity. Vernonia cognata extract attenuated oxidative and histopathological features induced by EtOH at all evaluated doses. Moreover, both studied doses of Vernonia cognata extract caused an increase in NPSH levels per se. However, only the dose of 2 g/kg reverted all macroscopic changes caused by EtOH toxicity. The protective effect of the extract could be attributed to antioxidant molecules present in the extract, such as flavonoids and phenolic acids, which were quantified by high performance liquid chromatography (HPLC). Thus, an antioxidant effect of the extract leads to a protection on gastric tissue. Our results indicate that Vernonia cognata hydroethanolic extract could have a beneficial role against EtOH toxicity by preventing oxidative stress and gastric tissue injury.
Asunto(s)
Antioxidantes/farmacología , Etanol/toxicidad , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Solventes/toxicidad , Vernonia/química , Animales , Catalasa/metabolismo , Mucosa Gástrica/metabolismo , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Estómago/efectos de los fármacos , Estómago/patología , Gastropatías/metabolismo , Gastropatías/patología , Gastropatías/prevención & controlRESUMEN
The combination of non-steroidal anti-inflammatory drugs with herbs having analgesic effects can increase their antinociceptive activity and limit their side effects. The aim of the present study was to examine the effects on inflammation and gastric injury in rats resulting from the interaction between naproxen and citral. Naproxen, citral, or fixed-dose naproxen-citral combinations were administered orally and their anti-inflammation (carrageenan-induced paw edema) and gastric damage were assessed in rats. The pharmacological interaction type was evaluated by the isobolographic analysis. Naproxen, citral, or combinations of naproxen and citral produced anti-inflammatory effects. The sole administration of naproxen produced significant gastric damage, but this effect was not obtained with either citral or combinations. ED(30) values were estimated for the individual drugs, and isobolograms were constructed. The derived theoretical ED(30) for the anti-inflammatory effect was 504.4 mg/kg; this was significantly higher than the observed experimental value (190.6 mg/kg). These results indicate that a synergistic interaction underlies the anti-inflammatory effect. The data suggests that the naproxen-citral combination can interact and to produce minor gastric damage and may have therapeutic advantages for the clinical treatment of inflammation.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Inflamación/tratamiento farmacológico , Monoterpenos/uso terapéutico , Naproxeno/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Gastropatías/prevención & control , Monoterpenos Acíclicos , Analgésicos/farmacología , Analgésicos/uso terapéutico , Animales , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/farmacología , Carragenina , Sinergismo Farmacológico , Edema/tratamiento farmacológico , Edema/etiología , Interacciones de Hierba-Droga , Masculino , Monoterpenos/farmacología , Naproxeno/efectos adversos , Naproxeno/farmacología , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Gastropatías/etiología , Gastropatías/patologíaRESUMEN
Ischemic preconditioning (IPC), a strategy used to attenuate ischemia-reperfusion injury, consists of brief ischemic periods, each followed by reperfusion, prior to a sustained ischemic insult. The purpose of the present study was to evaluate the local and systemic anti-inflammatory effects of hind limb IPC in male Wistar rat (200-250 g) models of acute inflammation. IPC was induced with right hind limb ischemia for 10 min by placing an elastic rubber band tourniquet on the proximal part of the limb followed by 30 min of reperfusion. Groups (N = 6-8) were submitted to right or left paw edema (PE) with carrageenan (100 µg) or Dextran (200 µg), hemorrhagic cystitis with ifosfamide (200 mg/kg, ip) or gastric injury (GI) with indomethacin (20 mg/kg, vo). Controls received similar treatments, without IPC (Sham-IPC). PE is reported as variation of paw volume (mL), vesical edema (VE) as vesical wet weight (mg), vascular permeability (VP) with Evans blue extravasation (µg), GI with the gastric lesion index (GLI; total length of all erosions, mm), and neutrophil migration (NM) from myeloperoxidase activity. The statistical significance (P < 0.05) was determined by ANOVA, followed by the Tukey test. Carrageenan or Dextran-induced PE and VP in either paw were reduced by IPC (42-58.7 percent). IPC inhibited VE (38.8 percent) and VP (54 percent) in ifosfamide-induced hemorrhagic cystitis. GI and NM induced by indomethacin were inhibited by IPC (GLI: 90.3 percent; NM: 64 percent). This study shows for the first time that IPC produces local and systemic anti-inflammatory effects in models of acute inflammation other than ischemia-reperfusion injury.
Asunto(s)
Animales , Masculino , Ratas , Cistitis/prevención & control , Edema/prevención & control , Miembro Posterior/irrigación sanguínea , Inflamación/prevención & control , Precondicionamiento Isquémico/métodos , Gastropatías/prevención & control , Enfermedad Aguda , Carragenina , Cistitis/inducido químicamente , Edema/inducido químicamente , Ifosfamida , Indometacina , Inflamación/inducido químicamente , Ratas Wistar , Gastropatías/inducido químicamenteRESUMEN
Ischemic preconditioning (IPC), a strategy used to attenuate ischemia-reperfusion injury, consists of brief ischemic periods, each followed by reperfusion, prior to a sustained ischemic insult. The purpose of the present study was to evaluate the local and systemic anti-inflammatory effects of hind limb IPC in male Wistar rat (200-250 g) models of acute inflammation. IPC was induced with right hind limb ischemia for 10 min by placing an elastic rubber band tourniquet on the proximal part of the limb followed by 30 min of reperfusion. Groups (N = 6-8) were submitted to right or left paw edema (PE) with carrageenan (100 microg) or Dextran (200 microg), hemorrhagic cystitis with ifosfamide (200 mg/kg, ip) or gastric injury (GI) with indomethacin (20 mg/kg, vo). Controls received similar treatments, without IPC (Sham-IPC). PE is reported as variation of paw volume (mL), vesical edema (VE) as vesical wet weight (mg), vascular permeability (VP) with Evans blue extravasation (microg), GI with the gastric lesion index (GLI; total length of all erosions, mm), and neutrophil migration (NM) from myeloperoxidase activity. The statistical significance (P < 0.05) was determined by ANOVA, followed by the Tukey test. Carrageenan or Dextran-induced PE and VP in either paw were reduced by IPC (42-58.7%). IPC inhibited VE (38.8%) and VP (54%) in ifosfamide-induced hemorrhagic cystitis. GI and NM induced by indomethacin were inhibited by IPC (GLI: 90.3%; NM: 64%). This study shows for the first time that IPC produces local and systemic anti-inflammatory effects in models of acute inflammation other than ischemia-reperfusion injury.
Asunto(s)
Cistitis/prevención & control , Edema/prevención & control , Miembro Posterior/irrigación sanguínea , Inflamación/prevención & control , Precondicionamiento Isquémico/métodos , Gastropatías/prevención & control , Enfermedad Aguda , Animales , Carragenina , Cistitis/inducido químicamente , Edema/inducido químicamente , Ifosfamida , Indometacina , Inflamación/inducido químicamente , Masculino , Ratas , Ratas Wistar , Gastropatías/inducido químicamenteRESUMEN
The aim of this study was to evaluate the protective effect of hydrogen sulfide (H(2)S) on ethanol-induced gastric lesions in mice and the influence of ATP-sensitive potassium (K(ATP)) channels, capsaicin-sensitive sensory afferent neurons, and transient receptor potential vanilloid (TRPV) 1 receptors on such an effect. Saline and L-cysteine alone or with propargylglycine, sodium hydrogen sulfide (NaHS), or Lawesson's reagent were administrated for testing purposes. For other experiments, mice were pretreated with glibenclamide, neurotoxic doses of capsaicin, or capsazepine. Afterward, mice received L-cysteine, NaHS, or Lawesson's reagent. After 30 min, 50% ethanol was administrated by gavage. After 1 h, mice were sacrificed, and gastric damage was evaluated by macroscopic and microscopic analyses. L-cysteine, NaHS, and Lawesson's reagent treatment prevented ethanol-induced macroscopic and microscopic gastric damage in a dose-dependent manner. Administration of propargylglycine, an inhibitor of endogenous H(2)S synthesis, reversed gastric protection induced by L-cysteine. Glibenclamide reversed L-cysteine, NaHS, or Lawesson's reagent gastroprotective effects against ethanol-induced macroscopic damage in a dose-dependent manner. Chemical ablation of sensory afferent neurons by capsaicin reversed gastroprotective effects of L-cysteine or H(2)S donors (NaHS or Lawesson's reagent) in ethanol-induced macroscopic gastric damage. Likewise, in the presence of the TRPV1 antagonist capsazepine, the gastroprotective effects of L-cysteine, NaHS, or Lawesson's reagent were also abolished. Our results suggest that H(2)S prevents ethanol-induced gastric damage. Although there are many mechanisms through which this effect can occur, our data support the hypothesis that the activation of K(ATP) channels and afferent neurons/TRPV1 receptors is of primary importance.
Asunto(s)
Contaminantes Atmosféricos/farmacología , Capsaicina/farmacología , Depresores del Sistema Nervioso Central/antagonistas & inhibidores , Depresores del Sistema Nervioso Central/toxicidad , Etanol/antagonistas & inhibidores , Etanol/toxicidad , Sulfuro de Hidrógeno/farmacología , Canales KATP/fisiología , Neuronas Aferentes/efectos de los fármacos , Gastropatías/inducido químicamente , Gastropatías/prevención & control , Alquinos/farmacología , Animales , Cisteína/farmacología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Mucosa Gástrica/patología , Glutatión/metabolismo , Gliburida/farmacología , Glicina/análogos & derivados , Glicina/farmacología , Hipoglucemiantes/farmacología , Canales KATP/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Ratones , Sustancias Protectoras/farmacología , Gastropatías/patología , Canales Catiónicos TRPV/fisiologíaRESUMEN
OBJECTIVE AND DESIGN: To investigate the role of non-protein sulfhydryl groups (NP-SH) and leukocyte adhesion in the protective effect of lipopolysaccharide (LPS) from Escherichia coli against indomethacin-induced gastropathy. MATERIALS OR SUBJECTS: Male Wistar rats were divided into four groups: saline, LPS, saline + indomethacin and LPS + indomethacin, with six rats in each group. TREATMENT: Rats were pretreated with LPS (300 microg/kg, by intravenous) or saline. After 6 h, indomethacin was administered (20 mg/kg, by gavage). METHODS: Three hours after treatments, rats were killed. Macroscopic gastric damage, gastric NP-SH concentration, myeloperoxidase (MPO) activity and mesenteric leukocyte adhesion (intravital microscopy) were assessed. Statistical analysis was performed using one-way analysis of variance followed by the Newman-Keuls test. Statistical significance was set at P < 0.05. RESULTS: LPS reduced the gastric damage, gastric MPO activity and increased gastric NP-SH concentration in indomethacin-induced gastropathy. LPS alone increased gastric NP-SH when compared to saline. Indomethacin increased leukocyte adhesion when compared to the saline, and LPS reduced indomethacin-induced leukocyte adhesion. In addition, LPS alone did not change leukocyte adhesion, when compared to the saline. CONCLUSION: LPS protective effect against indomethacin-induced gastropathy is mediated by an increase in the NP-SH and a decrease in leukocyte-endothelial adhesion.
Asunto(s)
Escherichia coli , Leucocitos/patología , Lipopolisacáridos/uso terapéutico , Gastropatías/metabolismo , Gastropatías/prevención & control , Compuestos de Sulfhidrilo/metabolismo , Animales , Adhesión Celular/fisiología , Modelos Animales de Enfermedad , Endotelio/patología , Endotelio/fisiología , Escherichia coli/metabolismo , Mucosa Gástrica/metabolismo , Indometacina/efectos adversos , Leucocitos/fisiología , Lipopolisacáridos/metabolismo , Masculino , Ratas , Ratas Wistar , Estómago/patología , Gastropatías/inducido químicamenteRESUMEN
Several plants are used in folk medicine to treat gastrointestinal disorders. Ananas ananassoides (Baker) L.B. Smith (Family Bromeliaceae) is a medicinal plant commonly used in the central region of Brazil against gastric pain. We evaluated two extracts (methanol [MeOH] and dichloromethane [DCM]) obtained from the leaves of A. ananassoides for their ability to protect the gastric mucosa against injuries caused by necrotizing agents (0.3 M HCl/60% ethanol, absolute ethanol, non-steroidal anti-inflammatory drugs, and pylorus ligation) in mice and rats. The best results were obtained after pretreatment with the DCM extract, whereas the MeOH extract did not show any significant anti-ulcerogenic activity but presented mutagenic action. The mechanism of action of the DCM extract suggested the effective participation of endogenous sulfhydryl group in the gastroprotective action. The data, taken together with the absence of acute toxicity and mutagenicity, indicate the apolar extract, instead of the polar, extract of A. ananassoides as a safe and potential new anti-ulcerogenic drug.