RESUMEN
Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.
Asunto(s)
Vesículas Extracelulares/metabolismo , Infecciones por Helicobacter/metabolismo , Helicobacter pylori/metabolismo , Gastropatías/metabolismo , Membrana Externa Bacteriana/metabolismo , Progresión de la Enfermedad , Vesículas Extracelulares/genética , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/patogenicidad , Humanos , Gastropatías/microbiología , Gastropatías/patologíaRESUMEN
To understand the molecular mechanisms involved in gastric disorders and regeneration, we need an in vitro tridimensional (3D) culture model, which can mimic the in vivo gastric microenvironment. A 3D coculture system named gastrosphere is proposed herein, composed of primary human gastric epithelial and stromal cells. The primary cultures were obtained from endoscopic gastric biopsies, and after mechanical and enzymatic dispersion, epithelial (HGE3) and stromal (HGS12) cells were expanded. After extensive immunocytochemical characterization, cells were seeded onto 96-well round bottom plates previously covered with 1% agarose. Cells were cultured in KM-F12 culture medium with 10% fetal bovine serum (FBS), antibiotics, and antimycotics, in humidified air at 37 °C and atmosphere containing 5% CO2 for 72 h or until spheres formation. Then gastrospheres were carefully transferred to a rotary cell culture system (RCCS-4), and maintained for 07, 14, 21, and 28 days. Gastrospheres were morphologically characterized by immunocytochemistry [cytokeratins (CK), vimentin, α-smooth muscle actin (α-SMA), laminin (LN), fibronectin (FN), and type IV collagen (CIV), proliferating cell nuclear antigen (PCNA)], and electron microscopy. In gastrospheres, the cytokeratin-positive epithelial cells were found in the outer layer, while vimentin-positive stromal cells were localized in the center of the gastrospheres. PCNA+ cells were mainly seen at the peripheral and in the intermediary region while nestin+ cells were also depicted in the latter zone. Scanning electron microscopy revealed groups of cohesive gastric cells at the periphery, while transmission electron microscopy demonstrated some differentiated mucous-like or zymogenic-like cells in the periphery and stromal structures located at the center of the 3D structures. Extracellular matrix was deposed between cells. Our data suggest that in vitro gastrospheres recapitulate the in vivo gastric microenvironment.
Asunto(s)
Técnicas de Cultivo de Célula , Técnicas de Cocultivo , Esferoides Celulares , Animales , Biomarcadores , Biopsia , Microambiente Celular , Células Epiteliales/citología , Células Epiteliales/metabolismo , Células Epiteliales/ultraestructura , Técnica del Anticuerpo Fluorescente , Mucosa Gástrica/citología , Mucosa Gástrica/metabolismo , Mucosa Gástrica/ultraestructura , Inmunohistoquímica , Ratones , Estómago , Gastropatías/etiología , Gastropatías/metabolismo , Gastropatías/patología , Células del Estroma/citología , Células del Estroma/metabolismo , Células del Estroma/ultraestructuraRESUMEN
Hydrogen sulfide (H2S) is a signaling molecule in the gastrointestinal tract. H2S production can derive from d-cysteine via various pathways, thus pointing to a new therapeutic approach: delivery of H2S to specific tissues. This study was designed to evaluate the concentration and effects of H2S (generated by d-amino acid oxidase [DAO] from d-cysteine) in the gastric mucosa and the protective effects against ethanol-induced lesions in mice. Mice were treated with l-cysteine or d-cysteine (100 mg/kg per os). Other groups received oral l-propargylglycine (cystathionine γ-lyase inhibitor, 100 mg/kg) or indole-2-carboxylate (DAO inhibitor), and 30 min later, received d- or l-cysteine. After 30 min, 50% ethanol (2.5 mL/kg, per os) was administered. After 1 h, the mice were euthanized and their stomachs excised and analyzed. Pretreatment with either l-cysteine or d-cysteine significantly reduced ethanol-induced lesions. Pretreatment of d-cysteine- or l-cysteine-treated groups with indole-2-carboxylate reversed the gastroprotective effects of d-cysteine but not l-cysteine. Histological analysis revealed that pretreatment with d-cysteine decreased hemorrhagic damage, edema, and the loss of the epithelium, whereas the administration of indole-2-carboxylate reversed these effects. d-Cysteine also reduced malondialdehyde levels but maintained the levels of reduced glutathione. Furthermore, pretreatment with d-cysteine increased the synthesis of H2S. Thus, an H2S-generating pathway (involving d-cysteine and DAO) is present in the gastric mucosa and protects this tissue from ethanol-induced damage by decreasing direct oxidative damage.
Asunto(s)
Antioxidantes/farmacología , Cisteína/farmacología , D-Aminoácido Oxidasa/metabolismo , Mucosa Gástrica , Sulfuro de Hidrógeno/metabolismo , Animales , Etanol/efectos adversos , Femenino , Mucosa Gástrica/química , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Glutatión/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones , Gastropatías/inducido químicamente , Gastropatías/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Species of Chresta genus- are recognized by the population of northeastern Brazil as traditional herbs used to treat gastric diseases and other disorders. AIM OF THE STUDY: This work aimed to find out the action mechanism of Chresta martii hydro alcoholic extract gastro protective effect in the model of ethanol-induced gastropathy. MATERIAL AND METHODS: Gastropathy was assessed by percentual damaged area determination in photographs of mice opened stomachs. Fasted mice treated with ethanol 99.9% (0.2 ml/animal, p.o.) were pre-treated with Chresta martii hydro alcoholic extract (HAE) (50, 100 or 200 mg/kg, p.o.), ranitidine (80 mg/kg, p.o.) or saline (5 ml/kg; p.o.) in different experimental sets, in which pharmacological tools (naloxone, indomethacin, N(ω)-Nitro-L-arginine methyl ester hydrochloride (L-NAME) or yohimbine) were added in order to clarify a possible action mechanism. Animals were sacrificed 30 min after ethanol challenge to stomach analysis. Determination of non-protein sulfhydryl groups and tissue hemoglobin, besides histological assessment (H&E) were taken to fully characterize the HAE gastro protective effect. RESULTS: HAE (100 and 200 mg/kg) was able to protect mucosa against ethanol gastropathy in presence of three (naloxone, indomethacin and L-NAME) of four antagonist/inhibitor tools. The HAE effect was reversed only by yohimbine, showing the alpha-2 adrenoceptors participation on gastro protective effect of this extract. HAE histological characteristics, NP-SH and Hb were compatible with the protective effects. CONCLUSIONS: HAE possesses gastroprotective effects in an ethanol-induced gastropathy model in mice, corroborating the traditional use of this family of plants to treat gastric disorders. This activity is mediated by alpha-2 adrenoceptors activation, but not by nitric oxide release, opioid receptor activation or prostaglandin synthesis. HAE also has antioxidant activity that is thought to either play a role in this biological activity or to be a byproduct of alpha-2 adrenergic complex activation.
Asunto(s)
Asteraceae , Extractos Vegetales/uso terapéutico , Sustancias Protectoras/uso terapéutico , Receptores Adrenérgicos alfa 2/metabolismo , Gastropatías/tratamiento farmacológico , Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Analgésicos Opioides , Animales , Clonidina/farmacología , Etanol , Flores , Hemoglobinas/metabolismo , Masculino , Ratones , Óxido Nítrico , Hojas de la Planta , Prostaglandinas , Gastropatías/inducido químicamente , Gastropatías/metabolismo , Gastropatías/patología , Compuestos de Sulfhidrilo/metabolismoRESUMEN
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.
Asunto(s)
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
CONTEXT: Portal hypertension is a complication secondary to cirrhosis that is characterized by increased blood flow and/or vascular resistance in the portal system, causing the appearance of a hyperdynamic collateral circulation. Partial portal vein ligation is an experimental model used in rats to study the pathophysiological mechanisms involved in pre-hepatic portal hypertension. Estrogen E2 is an antioxidant molecule with various physiological actions. OBJECTIVES: To evaluate the antioxidant activity of endogenous estrogen in an experimental model of partial portal vein ligation by comparing intact with castrated rats. METHODS: Twenty Wistar rats, weighing on average 250 g were used and divided into four groups: sham-operated (SO); intact (I) with partial portal vein ligation (I + PPVL), castrated (C) and castrated with partial ligation of the vein (C + PPVL). Day 1: castration or sham-operation; day 7, PPVL surgery; on day 15 post-PPVL, portal pressure in the mesenteric vein of rats was measured on polygraph Letica. Lipid peroxidation in the stomach was assessed using the technique of thiobarbituric acid reactive substances and activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase. Statistical analysis was done with ANOVA - Student-Newman-Keuls (mean ± SE), and P<0.05 was considered as significant. RESULTS: Portal pressure was significantly increased in C + PPVL as compared to the other groups. There was no significant difference in the group of intact rats. TBARS showed significant damage in C and C + PPVL in relation to others. Antioxidant enzymes were significantly increased in the castrated rats with subsequent PPVL as compared to the other groups. CONCLUSION: We suggest that estrogen E2 plays a protective role in intact compared with castrated rats because it presents hydrophenolic radicals in its molecule, thus acting as an antioxidant in this experimental model.
Asunto(s)
Antioxidantes/metabolismo , Estrógenos/metabolismo , Hipertensión Portal/metabolismo , Gastropatías/metabolismo , Animales , Modelos Animales de Enfermedad , Femenino , Hipertensión Portal/patología , Peroxidación de Lípido , Ovariectomía , Ratas , Ratas Wistar , Gastropatías/patología , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
CONTEXT: Portal hypertension is a complication secondary to cirrhosis that is characterized by increased blood flow and/or vascular resistance in the portal system, causing the appearance of a hyperdynamic collateral circulation. Partial portal vein ligation is an experimental model used in rats to study the pathophysiological mechanisms involved in pre-hepatic portal hypertension. Estrogen E2 is an antioxidant molecule with various physiological actions. OBJECTIVES: To evaluate the antioxidant activity of endogenous estrogen in an experimental model of partial portal vein ligation by comparing intact with castrated rats. METHODS: Twenty Wistar rats, weighing on average 250 g were used and divided into four groups: sham-operated (SO); intact (I) with partial portal vein ligation (I + PPVL), castrated (C) and castrated with partial ligation of the vein (C + PPVL). Day 1: castration or sham-operation; day 7, PPVL surgery; on day 15 post-PPVL, portal pressure in the mesenteric vein of rats was measured on polygraph Letica. Lipid peroxidation in the stomach was assessed using the technique of thiobarbituric acid reactive substances and activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase. Statistical analysis was done with ANOVA - Student-Newman-Keuls (mean ± SE), and P<0.05 was considered as significant. RESULTS: Portal pressure was significantly increased in C + PPVL as compared to the other groups. There was no significant difference in the group of intact rats. TBARS showed significant damage in C and C + PPVL in relation to others. Antioxidant enzymes were significantly increased in the castrated rats with subsequent PPVL as compared to the other groups. CONCLUSION: We suggest that estrogen E2 plays a protective role in intact compared with castrated rats because it presents hydrophenolic radicals in its molecule, thus acting as an antioxidant in this experimental model.
CONTEXTO: A hipertensão portal é uma complicação secundária à cirrose que tem como característica aumento do fluxo sanguíneo e/ou resistência vascular no sistema porta, causando o surgimento de uma circulação colateral hiperdinâmica. A ligadura parcial de veia porta é o modelo experimental utilizado em ratos para estudar os mecanismos fisiopatológicos envolvidos na hipertensão portal pré-hepática. O estrogênio E2 é uma molécula antioxidante com diferentes ações fisiológicas. OBJETIVOS: Verificar a ação antioxidante do estrogênio endógeno em modelo experimental de ligadura parcial de veia porta comparando ratas intactas com ratas castradas. MÉTODOS: Foram utilizadas 20 ratas Wistar, pesando em média 250 g, divididas em quatro grupos: "sham-operated" (SO); intactas com ligadura parcial da veia porta (I + LPVP); castradas (C) e castradas com ligadura parcial da veia porta (C + LPVP). No 1º dia: castração ou "sham-operated"; no 7º dia cirurgia de LPVP; no 15º dia após a LPVP, foi verificada a pressão portal na veia mesentérica das ratas, no polígrafo Letica. A lipoperoxidação no estômago foi avaliada através da técnica das substâncias reativas ao acido tiobarbitúrico e a atividade das enzimas antioxidantes superóxido dismutase, catalase e glutationa peroxidase. A análise estatística utilizada foi ANOVA - Student-Newmann-Keuls, (Média ± EP) e foi considerado significativo para P<0.05. RESULTADOS: A pressão portal mostrou aumento significativo no grupo C + LPVP em relação aos demais, não houve diferença significativa no grupo das ratas intactas. O TBARS mostrou dano estatisticamente significativo no grupo C e C + LPVP em relação aos demais. Quanto às enzimas antioxidantes, as ratas castradas e com posterior ligadura parcial de veia porta tiveram aumento significativo em relação às demais. CONCLUSÃO: Sugere-se que o estrogênio E2, por apresentar radicais hidrofenólicos em sua molécula, desempenha um papel protetor nas ratas intactas em comparação com as castradas, agindo assim, como antioxidante, neste modelo experimental.
Asunto(s)
Animales , Femenino , Ratas , Antioxidantes/metabolismo , Estrógenos/metabolismo , Hipertensión Portal/metabolismo , Gastropatías/metabolismo , Modelos Animales de Enfermedad , Hipertensión Portal/patología , Peroxidación de Lípido , Ovariectomía , Ratas Wistar , Gastropatías/patología , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Pluchea sagittalis, an herbaceous plant widely distributed in South America, is used in folk medicine for the treatment of digestive diseases and inflammation. AIM OF THE STUDY: This study was designed to investigate the antinociceptive and gastroprotective effects of the ethanolic extract (EE) of aerial parts from Pluchea sagittalis in rodents. MATERIALS AND METHODS: The antinociceptive effects of EE was evaluated in mice after oral administration in chemical tests (acetic-acid, glutamate and formalin) or by biting behavior following intrathecal administration of cytokines such as interleukin-1beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) in mice. Furthermore, rats were treated with EE and subsequently exposed to acute gastric lesions induced by 80% ethanol. Afterwards the gastric lesion extension and the mucus levels of gastric mucosa were measured. RESULTS: The oral administration of EE showed a dose-dependent inhibition of acetic acid-induced abdominal constrictions and glutamate-induced pain in mice, with ID(50) values of 624.0 (523.0-746.0) mg/kg and 368.0 (216.0-628.0) mg/kg, respectively. In the formalin test, the EE also produced significant inhibition of the inflammatory phase, with an ID(50) value of 411.0 (183.0-721.0) mg/kg; however, it was ineffective in the neurogenic phase caused by formalin. In addition, oral treatment with EE caused a significant inhibition of biting behavior induced by i.t. injection of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). The antinociception caused by the EE (300 mg/kg, p.o.) was not reversed by naloxone (1 mg/kg, i.p.) when assessed in the acetic acid writhing test. The EE (300-1000 mg/kg, p.o.) did not affect the motor coordination of animals in an open-field model. Oral treatment with the EE protected rats against gastric lesions induced by ethanol, with an ID(50) value of 55.0 (46.6-64.9) mg/kg, and increased the mucus levels of gastric mucosa to levels found in the non-lesioned group. CONCLUSIONS: The mechanism by which the extract produced antinociception still remains unclear, but this effect seems to be primarily related to the modulation or inhibition of the action of pro-inflammatory mediators. Furthermore, these data support, at least in part, the ethnomedical use of Pluchea sagittalis.
Asunto(s)
Analgésicos/uso terapéutico , Asteraceae , Mucosa Gástrica/efectos de los fármacos , Fármacos Gastrointestinales/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Gastropatías/tratamiento farmacológico , Dolor Abdominal/inducido químicamente , Dolor Abdominal/tratamiento farmacológico , Analgésicos/farmacología , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Conducta Animal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Fármacos Gastrointestinales/farmacología , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Masculino , Ratones , Naloxona/farmacología , Componentes Aéreos de las Plantas , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Gastropatías/metabolismo , Gastropatías/patologíaRESUMEN
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
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
The effects of Matricaria recutita and alpha-bisabolol, a bioactive component from Chamomile species, were investigated against gastric damage induced by absolute ethanol (96%, 1 mL per animal) in rats. The effects of M. recutita extract and alpha-bisabolol on gastric mucosal damage were assessed by determination of changes in mean gastric lesion area. Mechanistic studies were carried out at with 100 mg=kg alpha-bisabolol. We further examined the possible participation of prostaglandins, nitric oxide, and KATP+ channels in its mechanism. M. recutita reduced gastric damage in all doses tested. Alpha-bisabolol at oral doses of 50 and 100 mg=kg markedly attenuated the gastric lesions induced by ethanol to the extent of 87% and 96%, respectively. Pretreatments with the nitric oxide antagonist N-nitro-l-arginine methyl ester (10 mg=kg, i.p.) or with indomethacin, an inhibitor of cyclooxygenase, failed to block effectively the gastroprotective effect of alpha-bisabolol. Furthermore, the alpha-bisabolol effect was significantly reduced in rats pretreated with glibenclamide, an inhibitor of KATP+ channel activation. Thus we provide evidence that alpha-bisabolol reduces the gastric damage induced by ethanol, at least in part, by the mechanism of activation of KATP+ channels.
Asunto(s)
Canales KATP/metabolismo , Matricaria/química , Óxido Nítrico/metabolismo , Extractos Vegetales/administración & dosificación , Prostaglandinas/metabolismo , Sesquiterpenos/administración & dosificación , Gastropatías/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Humanos , Masculino , Sesquiterpenos Monocíclicos , Distribución Aleatoria , Ratas , Gastropatías/metabolismoRESUMEN
The effect of lipopolysaccharide (LPS) in gastric protection has not been elucidated, but ATP-sensitive potassium (K(ATP)) channels are known to be involved in gastric defense. We evaluated the effect of LPS administration on indomethacin-induced gastropathy, and the role of K(ATP) channels in this event. Rats received intravenous (i.v.) LPS administration. After 1/2, 6, 24 or 48 h, indomethacin was injected. 3H later, gastric damage and myeloperoxidase activity were determined. Another group received LPS and 5 h later, glibenclamide, diazoxide or glibenclamide plus diazoxide. After 1 h, the rats received indomethacin and 3 h later, gastric damage and myeloperoxidase activity were evaluated. LPS reduced dose dependently gastric damage and myeloperoxidase activity induced by indomethacin. Glibenclamide reversed this LPS effect on indomethacin-induced gastropathy. Glibenclamide plus diazoxide administration did not change this LPS effect. Thus LPS has a protective effect against indomethacin-induced gastropathy, probably through activation of K(ATP) channels.
Asunto(s)
Indometacina/toxicidad , Lipopolisacáridos/farmacología , Canales de Potasio de Rectificación Interna/fisiología , Gastropatías/prevención & control , Análisis de Varianza , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/toxicidad , Glucemia/metabolismo , Diazóxido/administración & dosificación , Diazóxido/farmacología , Escherichia coli/química , Gliburida/administración & dosificación , Gliburida/farmacología , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacología , Indometacina/administración & dosificación , Inyecciones Intravenosas , Recuento de Leucocitos , Lipopolisacáridos/administración & dosificación , Masculino , Peroxidasa/metabolismo , Canales de Potasio de Rectificación Interna/agonistas , Canales de Potasio de Rectificación Interna/antagonistas & inhibidores , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/farmacología , Ratas , Ratas Wistar , Gastropatías/inducido químicamente , Gastropatías/metabolismoRESUMEN
Ureases are enzymes from plants, fungi and bacteria that catalyze the hydrolysis of urea to form ammonia and carbon dioxide. While fungal and plant ureases are homo-oligomers of 90-kDa subunits, bacterial ureases are multimers of two or three subunit complexes. We showed that some isoforms of jack bean urease, canatoxin and the classical urease, bind to glycoconjugates and induce platelet aggregation. Canatoxin also promotes release of histamine from mast cells, insulin from pancreatic cells and neurotransmitters from brain synaptosomes. In vivo it induces rat paw edema and neutrophil chemotaxis. These effects are independent of ureolytic activity and require activation of eicosanoid metabolism and calcium channels. Helicobacter pylori, a Gram-negative bacterium that colonizes the human stomach mucosa, causes gastric ulcers and cancer by a mechanism that is not understood. H. pylori produces factors that damage gastric epithelial cells, such as the vacuolating cytotoxin VacA, the cytotoxin-associated protein CagA, and a urease (up to 10% of bacterial protein) that neutralizes the acidic medium permitting its survival in the stomach. H. pylori whole cells or extracts of its water-soluble proteins promote inflammation, activate neutrophils and induce the release of cytokines. In this paper we review data from the literature suggesting that H. pylori urease displays many of the biological activities observed for jack bean ureases and show that bacterial ureases have a secretagogue effect modulated by eicosanoid metabolites through lipoxygenase pathways. These findings could be relevant to the elucidation of the role of urease in the pathogenesis of the gastrointestinal disease caused by H. pylori.
Asunto(s)
Canavalia/enzimología , Eicosanoides/metabolismo , Infecciones por Helicobacter/microbiología , Helicobacter pylori/enzimología , Proteínas de Plantas/biosíntesis , Toxinas Biológicas/biosíntesis , Ureasa/biosíntesis , Animales , Relación Dosis-Respuesta a Droga , Enfermedades Duodenales/metabolismo , Enfermedades Duodenales/microbiología , Infecciones por Helicobacter/metabolismo , Helicobacter pylori/patogenicidad , Humanos , Proteínas de Plantas/farmacología , Gastropatías/metabolismo , Gastropatías/microbiología , Toxinas Biológicas/farmacologíaRESUMEN
Ureases are enzymes from plants, fungi and bacteria that catalyze the hydrolysis of urea to form ammonia and carbon dioxide. While fungal and plant ureases are homo-oligomers of 90-kDa subunits, bacterial ureases are multimers of two or three subunit complexes. We showed that some isoforms of jack bean urease, canatoxin and the classical urease, bind to glycoconjugates and induce platelet aggregation. Canatoxin also promotes release of histamine from mast cells, insulin from pancreatic cells and neurotransmitters from brain synaptosomes. In vivo it induces rat paw edema and neutrophil chemotaxis. These effects are independent of ureolytic activity and require activation of eicosanoid metabolism and calcium channels. Helicobacter pylori, a Gram-negative bacterium that colonizes the human stomach mucosa, causes gastric ulcers and cancer by a mechanism that is not understood. H. pylori produces factors that damage gastric epithelial cells, such as the vacuolating cytotoxin VacA, the cytotoxin-associated protein CagA, and a urease (up to 10 percent of bacterial protein) that neutralizes the acidic medium permitting its survival in the stomach. H. pylori whole cells or extracts of its water-soluble proteins promote inflammation, activate neutrophils and induce the release of cytokines. In this paper we review data from the literature suggesting that H. pylori urease displays many of the biological activities observed for jack bean ureases and show that bacterial ureases have a secretagogue effect modulated by eicosanoid metabolites through lipoxygenase pathways. These findings could be relevant to the elucidation of the role of urease in the pathogenesis of the gastrointestinal disease caused by H. pylori.
Asunto(s)
Humanos , Animales , Canavalia/enzimología , Eicosanoides/metabolismo , Infecciones por Helicobacter/microbiología , Helicobacter pylori/enzimología , Proteínas de Plantas/biosíntesis , Ureasa/biosíntesis , Relación Dosis-Respuesta a Droga , Enfermedades Duodenales/metabolismo , Enfermedades Duodenales/microbiología , Infecciones por Helicobacter/metabolismo , Gastropatías/metabolismo , Gastropatías/microbiologíaRESUMEN
In a retrospective five years study of gastric wall tumors, we selected the type 1 heterotopic pancreas. The assessment of fibrosis and inflammatory infiltrate were performed. Also the immunohistochemical evaluation with monoclonal antibodies for insulin, glucagon, p substance, somatostatin, gastrin and antichimotrypsin. None of the case showed remarkable fibrosis or inflammatory infiltrate. All the Langerhans's islets stained positive for 2 or 3 hormones, gastrin and antichimotrypsin were always negative. These findings are comparable with others previously reported, but no cases of evaluation of islet's gastrin exist in the literature reviewed.
Asunto(s)
Coristoma/metabolismo , Islotes Pancreáticos/metabolismo , Páncreas , Hormonas Pancreáticas/análisis , Gastropatías/metabolismo , Anciano , Coristoma/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Through the efforts of Correa, Cuello, Haenszel, Tannenbaum and others it was learned that the incidence of gastric cancer in certain areas of Narino (Colombia) was among the highest in the world. These areas of high risk for gastric cancer were adjacent to an area of substantially lower risk. Gastric biopsies from healthy volunteers residing in the "high risk" area exhibited a greater incidence of superficial gastritis and chronic atrophic gastritis with and without intestinal metaplasia than those from the low risk area. The latter pathological finding is considered to be a precursor lesion to gastric cancer. Volunteers from the "low risk" area as well as individuals from Cali in the coastal region and Cartegena on the coast, also exhibited a similar spectrum of pathology but at a substantially reduced frequency. Natives of both cities were also at lower risk for gastric cancer than inhabitants of Narino. It was found that the water supply of the "high risk" area contained a higher concentration of nitrate than water in the "low risk" area. Correa et al. hypothesized that the high nitrate concentrations of well water contributed to the formation of N-nitroso compounds in the stomachs of these individuals early in life. The occurrence of this putative carcinogen in combination with the abrasive action of dietary grains contributed to a series of mutations in the gastric epithelium progressing through a sequence of pathologic changes, loss of gastric acid and culminating in gastric cancer. In the current report individuals in a Medellin population who were admitted with abdominal complaints and were found to be iron deficient exhibited the same spectrum of gastric pathology described by previous investigators. Superficial gastritis, chronic atrophic gastritis and achlorhydria have also been described in association with chronic iron deficiency (and/or associated nutritional defects) per se. The development of these lesions are likely to occur within the first two decades of life when iron requirements are maximal. It is suggested that these changes preceed the development of gastric cancer. Bacterial colonization of the achlorhydric stomach may facilitate nitrate reduction and the formation of a putative carcinogen N-nitroso compound(s) from nitrate in the water supply. Additionally, the effects of chronic iron deficiency on host immune defense may compromise these mechanisms and permit tumor growth with minimal immune intervention.