955 resultados para ENDOGENOUS HISTAMINE
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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We studied the direct effects of ethanol and its metabolites on the guinea pig lung mast cell, and the alterations caused in the histamine release induced by different stimuli. Guinea pig lungs cells dispersed by collagenase were used throughout. High concentrations of ethanol (100 mg/ml), acetaldehyde (0.3-3 mg/ml) and acetic acid (3 mg/ml) induced histamine release that was not inhibited by sodium cyanide (0.3 mM). Lower concentration of ethanol (10 mg/ml) and acetic acid (0.3 mg/ml), but not acetaldehyde, inhibited the histamine release induced by antigen and ionophore A23187. The histamine release induced by phorbol 12-miristate 13-acetate (1 mu M) was also inhibited by ethanol (10 mg/ml). Changes in the levels of calcium, glucose and phosphatidic acid did not influence the effect of ethanol. We conclude that high doses of ethanol, acetaldehyde, and acetic acid cause a cytotoxic histamine release by independent mechanisms. Low concentrations of acetic acid inhibit the histamine release by pH reduction. Ethanol acts by a generalized effect that is independent of calcium and glucose suggesting a nonspecific effect that, nevertheless, is not cytotoxic since it can be reversed by washing the cells. (C) 2000 Elsevier B.V. All rights reserved.
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Aim of the study: Cissus sicyoides L. is a medicinal plant popularly known in Brazil against various diseases and the research interest in this plant is justifiable because of its potential medicinal value in stomachache and gastric ulcer.Materials and methods: The methanolic extract obtained from the leaves of Cissus sicyoides (Cc) was evaluated for the ability to protect the gastric mucosa against injuries caused by necrotizing agents (0.3 M HCl/60% EtOH, absolute ethanol, piroxicam and pylorus ligature) in rodents. We also evaluated microcirculation, antioxidant action and participation of NO (nitric oxide) and sulfhydryls (SH) groups in the Cc gastroprotective action.Results: Administration of Cc significantly reduced gastric lesions induced by different ulcerogenic agents in rodents. This extract administered by oral route significantly increased gastric volume without exerting antisecretory effect. The Cc effect involved an increase of the defense mechanism of the gastrointestinal mucosa such as NO and SH groups that prevent and attenuate the ulcer process. The Cc also has antioxidant property against oxidative stress but does not modify microcirculation response in gastric mucosa.Conclusions: These results confirmed the traditional use of Cissus sicyoides for the treatment of gastric ulcer. (C) 2008 Elsevier B.V. All rights reserved.
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The present study reveals the pharmacological action of Serjania erecta Radlk. (Family Sapindaceae), an important medicinal plant species used in the Brazilian Pantanal against gastric pain. The methanolic (Me) and chloroformic (Se) extracts obtained from leaves of S. erecta were challenged by a very strong necrotizing agent in rodents, absolute ethanol. Se was also confronted with a nitric oxide synthase inhibitor (N(G)-nitro-l-arginine methyl ester), a capsaicin cation channel transient receptor potential vanilloid type 1 antagonist (ruthenium red), or a sulfhydryl-blocker (N-ethylmaleimide) to evaluate the participation of these cytoprotective factors in gastroprotection. In an in vivo experimental model, Me and Se presented several degrees of gastroprotective action without signs of acute toxicity. The best gastroprotective effect was restricted to all doses of Se. The mechanisms involving the gastroprotective action of Se are related to an augmented defense mechanism of the gastrointestinal mucosa consisting of sensory neurons, nitric oxide, and sulfhydryl groups that prevent and attenuate the ulcer process. The presence of polyisoprenoids in the Se explains the potent gastroprotective action of this medicinal species. Effective gastroprotective action and the absence of acute toxicity indicate this species may be a promising herbal drug against gastric disease.
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Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, the most prevalent deep mycosis in Latin America. Production of eicosanoids during fungal infections plays a critical role on fungal biology as well as on host immune response modulation. The purpose of our study was to assess whether P. brasiliensis strains with different degree of virulence (Pb18, Pb265, Bt79, Pb192) produce prostaglandin E-x (PGE(x)). Moreover, we asked if P. brasiliensis could use exogenous sources of arachidonic acid (AA), as well as metabolic pathways dependent on cyclooxygenase (COX) enzyme, as reported for mammalian cells. A possible association between this prostanoid and fungus viability was also assessed. Our results showed that all strains, independently of their virulence, produce high PGE(x) levels on 4 h culture that were reduced after 8 h. However, in both culture times, higher prostanoid levels were detected after supplementation of medium with exogenous AA. Treatment with indomethacin, a COX inhibitor, induced a reduction on PGEx, as well as in fungus viability. The data provide evidence that P. brasiliensis produces prostaglandin-like molecules by metabolizing either endogenous or exogenous AA. Moreover, the results suggest the involvement of these mediators on fungal viability.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Annexin 1 (ANXA1), galectin-1 (Gal-1) and galectin-3 (Gal-3) proteins have been identified as important mediators that promote or inhibit leukocyte migration. The expression of these proteins was studied in human neutrophils and endothelial cells (ECs) during a transmigration process induced by IL-8. Upon neutrophil adhesion to EC, a significant increase in the cleaved ANXA1 (LCS3, raised against all ANXA1 isoforms) expression was detected in the plasma membrane of adhered neutrophils and ECs compared to intact ANXA1 isoform (LCPS1, against N-terminus of protein). Adherent neutrophils had elevated Gal-3 levels in the nucleus and cytoplasm, and ECs in their plasma membranes. In contrast, a decrease in the total amounts of Gal-1 was detected in migrated compared to non-migrated neutrophils. Therefore, ANXA1 and Gal-3 changed in their content and localization when neutrophils adhere to endothelia, suggesting a process of sensitive-balance between two endogenous anti- and pro-inflammatory mediators. (c) 2006 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Pradosia huberi is a medicinal plant very common in the Amazonian forest population. The research interest in this plant is justifiable because of its potential medicinal value in gastritis and gastric ulcer mentioned in local folk medicine. In this paper, we evaluated the acute toxicity and antiulcerogenic effect of a hydroalcoholic extract (HAE) obtained from Pradosia huberi barks in rodents. No acute toxicological sign or symptom was observed in animals treated with the highest dose (5000 mg/kg, p.o.) of Pradosia huberi. In the HCl/EtOH-induced gastric ulcer model, HAE demonstrated significant inhibition of the ulcerative lesion index by 73% (500 mg/kg) and 88% (1000 mg/kg), respectively, in relation to the control value (p < 0.05). The gastric damage induced by absolute ethanol in rats was effectively reduced by 84, 88 and 81% (250, 500 and 1000 mg/kg) when compared with the control group (p < 0.01). In the NSAID-induced lesion model, HAE also showed antiulcerogenic effect with decrease in gastric lesions of 56% (250 mg/kg), 57% (500 mg/kg) and 67% (1000 mg/kg) when compared with animals treated with vehicle (p < 0.05). In the gastric ulcer induced by pylorus ligature model, the administration of HAE by oral and intraduodenal routes inhibited the gastric lesion index by 79 and 52% (500 mg/kg), respectively. HAE administered orally or intraduodenally was able to change gastric juice parameters (pH, volume and acid output) as well as those treated with cimetidine. The treatment with HAE (p.o.) significantly increased gastric volume, the pH values and promoted reduced acid output (1) < 0.01). By comparative effect (intraduodenal and oral route), we observed that HAE was better for local activity in gastric mucosa than in systemic action. HAE also has a non-specific activity when found to be the inhibitor of intestinal motility (p > 0.01). The mechanism of action of HAE did not seem to be related to the NO-inhibitor but showed the participation of endogenous sulphydryl group in the gastroprotective action. (C) 2005 Elsevier B.V.. All rights reserved.
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Several plants are used in folk medicine to treat gastrointestinal disorders. Mouriri pusa Gardn. (Melastomataceae) is a medicinal plant commonly used in the central region of Brazil against gastric ulcer. Two organic extracts methanolic (MeOH) and dichloromethane (DCM) obtained by sequential extraction from the leaves of Mouriri pusa were evaluated for their ability to protect the gastric mucosa against injuries caused by necrotizing agents (0.3 M HCl/60% EtOH, absolute ethanol, non-steroidal anti-inflammatory drug, stress and pylorus ligature) in mice and rats. The best results were obtained after pretreatment with MeOH extract whereas the DCM extract did not show the same significant antiulcerogenic activity. No acute toxicity was observed in animals treated with 5 g/kg, p.o. of MeOH extract. The mechanism involving the antiulcerogenic action of MeOH extract seemed to be related to NO generation and also suggested the effective participation of endogenous sulfhydryl group in the gastroprotective action. Phytochemical investigation of the MeOH extract of Mouriri pusa yielded tannins, flavonoids and (-)-epicatechin. The presence of these phenolic compounds probably would explain the antiulcerogenic effect of the polar extract of Mouriri pusa leaves. (c) 2006 Elsevier B.V.. All rights reserved.
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The tea made with leaves and stems of plant Anchietia salutaris is traditionally used in Brazil to treat allergies. We examined the effects of a crude aqueous extract and of purified fractions of this plant on the histamine release induced in rat and guinea pig tissues. The crude extract (3-10 mu g/ml) inhibits the histamine release induced by compound 48/80 (0.5 mu g/ml) and antigen in rat peritoneal mast cells. The inhibition is significant after 10 s of preincubation and is completed after 3 min. The crude extract dissolved in the perfusion fluid (1-30 mu g/ml) also inhibits the histamine release induced in guinea pig heart by cardiac anaphylaxis and in hearts from pretreated animals (10-100 mg/kg i.p.). In pretreated animals, the effect manifests after 3 h, is maximum after 12 h and disappears after 48 h. The histamine release induced in isolated guinea pig heart by ionophore A23187 is inhibited by similar doses as in antigen-induced histamine release. Extraction with solvents concentrated the active principle (s) in the hexane fractions, as demonstrated by the inhibition of the histamine release induced by antigen in isolated cells from guinea pig heart dispersed with collagenase. In subfractions produced by the fractionation of the hexane fraction, the active principle(s) concentrated in the subfractions obtained by extraction with hexane and ethyl acetate, which shows the low polarity of the compound(s). The same subfractions that inhibit the histamine release induced by antigen in cells from guinea pig heart also inhibit pulmonary cells. Our result show that A. salutaris contains low-polarity compound(s) that inhibit the histamine release induced by three different mechanisms in mast cells from two animal species. These facts suggest that the active principle(s) of A, salutaris could be useful in the treatment of allergies and/or as a tool for the study of mast cell secretions.
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We studied here the effect of a wide range of adenosine concentration and time of preincubation, on the histamine release induced in the guinea pig mast cells by different stimulus. Adenosine (10(-5)-10(-3) M) potentiated the histamine release induced by antigen in the guinea pig heart (isolated and dispersed tissue) and lung mast cells but not induced by ionophore A23197. The potentiation caused by adenosine (10(-4) M) was maximum after 1-3 min of preincubation and is probably an extracellular effect since it was not avoided by dipyridamol (3 x 10(-7)-10(-6) M) that inhibit the uptake of adenosine. Similar potentiation was also produced by the adenosine mimetic 2-chloroadenosine (10(-5) M) and both effects were inhibited by 8-phenyltheophylline indicating an effect on the type A receptors. It is suggested that the adenosine potentiation may not be related to changes on the cyclic AMP levels. (C) 2000 Academic Press.