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1.
Molecules ; 27(11)2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35684410

RESUMO

Pseudoallergic reactions are hypersensitivity reactions mediated by an IgE-independent mechanism. Since allantoin (AT)-mediated pseudoallergy has not been studied, in this study, our objective is to investigate the anti-pseudoallergy effect of AT and its underlying mechanism. In vitro, ß-hexosaminidase (ß-Hex) and histamine (HIS) release assays, inflammatory cytokine assays, toluidine blue staining, and F-actin microfilament staining were used to evaluate the inhibitory effect of AT in RBL-2H3 cells stimulated with Compound 48/80 (C48/80). Western blot analysis is further performed to investigate intracellular calcium fluctuation-related signaling pathways. In vivo, Evans Blue extraction, paw swelling, and the diameter of Evans Blue extravasation were evaluated, and skin tissues are examined for histopathological examination in mice with passive cutaneous anaphylaxis (PCA) induced by C48/80. Body temperature is measured, and the levels of cytokines are further determined by ELISA kits in mice with active systemic anaphylaxis (ASA) induced by C48/80. The results show that AT dose-dependently inhibited degranulation in C48/80-stimulated RBL-2H3 cells by inhibiting ß-Hex and HIS release, reducing the levels of TNF-α, IL-8, and MCP-1, inhibiting shape changes due to degranulation and disassembling the F-actin cytoskeleton. Furthermore, AT dose-dependently inhibits the phosphorylation of PLCγ and IP3R. In vivo, AT decreased Evans Blue extravasation, paw swelling, and the diameter of Evans Blue extravasation and significantly ameliorate pathological changes and mast cell degranulation in C48/80-induced PCA. Furthermore, AT help the mice recover from the C48/80-induced decrease in body temperature and decreased the levels of cytokines in C48/80-treated ASA mice. Our results indicate that allantoin inhibits compound 48/80-induced pseudoallergic reactions. AT has the potential to be used in IgE-independent anti-allergic and anti-inflammatory therapies.


Assuntos
Anafilaxia , p-Metoxi-N-metilfenetilamina , Alantoína/metabolismo , Anafilaxia/induzido quimicamente , Anafilaxia/tratamento farmacológico , Anafilaxia/metabolismo , Animais , Degranulação Celular , Citocinas/metabolismo , Edema/patologia , Azul Evans/efeitos adversos , Azul Evans/metabolismo , Imunoglobulina E/metabolismo , Mastócitos , Camundongos , beta-N-Acetil-Hexosaminidases/metabolismo , p-Metoxi-N-metilfenetilamina/efeitos adversos
2.
Braz J Cardiovasc Surg ; 37(1): 20-28, 2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35274519

RESUMO

INTRODUCTION: There are many reasons to believe that the nitric oxide/guanosine 3'5' - cyclic monophosphate (or NO/cGMP) pathway on vasoplegic states is underestimated. To study indigo carmine (IC) as an alternative to methylene blue was the investigation rationale. METHODS: The IC (3mg/kg intravenous infusion) study protocol included five experimental groups; 1) Control group - saline was injected at 0 and 10 minutes; 2) IC group - IC was injected at 0 and saline at 10 minutes; 3) compound 48/80 (C48/80) group - C48/80 was injected at 0 minute and saline at 10 minutes; 4) C48/80 + IC group - C48/80 was injected at 0 minute and IC at 10 minutes; and 5) IC + C48/80 group - IC was injected at 0 minute and C48/80 at 10 minutes. The studies were carried out by registering and measuring hemodynamic and blood gasometric parameters, including continuous cardiac output. RESULTS: 1) The effects of the drugs (IC and C48/80) were more evident in the first 20 minutes of recording; 2) hypotensive responses were more pronounced in the C48/80 groups; 3) IC isolated or applied before C48/80 caused transient pulmonary hypertension; and 4) after the first 20 minutes, the pressure responses showed stability with apparent hypotension more pronounced in the C48/80 groups. Clinical observations showed significant hemodynamic instability and catastrophic anaphylactic reactions (agitation, pulmonary hypertension, severe bronchospasm, urticaria, high-intensity cyanosis, violent gastric hypersecretion, and ascites). CONCLUSION: A global results analysis showed differences between groups only in the first 20 minutes of the experiments.


Assuntos
Anafilaxia , Vasoplegia , Anafilaxia/tratamento farmacológico , Animais , Hemodinâmica , Humanos , Índigo Carmim/efeitos adversos , Óxido Nítrico , Suínos , p-Metoxi-N-metilfenetilamina/efeitos adversos
3.
Cell Immunol ; 358: 104239, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33129497

RESUMO

Roxithromycin (ROX) is a macrolide antibiotic with a variety of immunological effects. Mast cells (MCs) play a key role in host defense, mediating hypersensitivity and pseudo-allergic reactions. Mas-related G protein-coupled receptor X2 (MrgprX2) is the main receptor related to pseudo-allergy. In this study, we investigated the anti-pseudo-allergy effect of ROX and its underlying mechanism. The effects of ROX on passive cutaneous anaphylaxis (PCA) and active systemic allergy were examined, degranulation, Ca2+ influx, and cytokine release were studied in vivo and in vitro. Interactions between ROX and MrgprX2 protein were also detected through surface plasmon resonance. The PCA and active systemic allergy induced by compound 48/80 were inhibited by ROX. An intermolecular interaction was detected between the ROX and MrgprX2 protein. In conclusion, ROX could inhibit pseudo-allergic reactions, and this effect involves the Ca2+/PLC/IP3 pathway of MrgprX2. This study provides new insight into the anti-pseudo-allergy effects of ROX.


Assuntos
Hipersensibilidade/tratamento farmacológico , Receptores Acoplados a Proteínas G/metabolismo , Roxitromicina/farmacologia , Anafilaxia/induzido quimicamente , Animais , Antialérgicos/farmacologia , Degranulação Celular/imunologia , Citocinas/metabolismo , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Proteínas do Tecido Nervoso/imunologia , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Receptores Acoplados a Proteínas G/efeitos dos fármacos , Receptores Acoplados a Proteínas G/imunologia , Receptores de Neuropeptídeos/imunologia , Roxitromicina/metabolismo , p-Metoxi-N-metilfenetilamina/efeitos adversos , p-Metoxi-N-metilfenetilamina/metabolismo
4.
Curr Med Sci ; 40(4): 761-766, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32862388

RESUMO

Mechanisms of pruritus are implicated in the dysregulation of the metabolites in the spinal cord. We investigated pruritus behavioral testing in three groups of young adult male C57Bl/6 mice, including one group treated with normal saline, while the other groups intradermally injected with α-Me-5-HT (histamine-independent pruritogen), compound 48/80 (histamine-dependent pruritogen) at the nape skin of the neck, respectively. Proton nuclear magnetic resonance spectroscopy (MRS) was used to compare spinal metabolites from the vertebral cervical among three groups, and to study the association of spinal metabolite ratio and pruritus intensity. The MRS-measured N-acetylaspartate-to-myoinositol ratio (NAA/Ins) was significantly correlated with the number of scratches between normal saline group and 48/80 group or α-Me-5-HT group (both P<0.0001), indicating that NAA/Ins may be a robust surrogate marker of histamine-independent/dependent pruritogen. There was significant difference in Glu/Ins between normal saline group and 48/80 group (P=0.017), indicating that Glu/Ins may be a surrogate marker of histamine-dependent pruritogen, while GABA/Ins was highly significantly different between normal saline group and α-Me-5-HT group (P=0.008), suggesting that GABA/Ins may be a surrogate marker of histamine-independent pruritogen. MRS may reflect the extent of pruritus intensity elicited by α-Me-5-HT and compound 48/80 with sensitivity similar to the number of scratches, and above potential markers need to be further validated in pre-clinical and clinical treatment trials.


Assuntos
Ácido Aspártico/análogos & derivados , Inositol/análise , Prurido/diagnóstico por imagem , Serotonina/análogos & derivados , Medula Espinal/diagnóstico por imagem , p-Metoxi-N-metilfenetilamina/efeitos adversos , Animais , Ácido Aspártico/análise , Biomarcadores/análise , Injeções Intradérmicas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Espectroscopia de Prótons por Ressonância Magnética , Prurido/induzido quimicamente , Serotonina/efeitos adversos , Medula Espinal/química
5.
Vet Dermatol ; 30(4): 325-e91, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31038263

RESUMO

BACKGROUND: Scratching behaviours associated with intradermal (i.d.) injection of pruritogens such as histamine and compound 48/80 into the skin of mice and humans is the commonly used model to advance itch research and drug development. The predictive validity of this model is poorly documented in dogs. OBJECTIVES: To evaluate the dose-dependent effects of pruritogenic substances, each with a different mechanism of action, in healthy dogs. ANIMALS: Ten healthy laboratory beagles. METHODS AND MATERIALS: All dogs were video-recorded for 30 min post-injection (mpi) of i.d. goat anti-canine IgE (4 and 25 µg/site), histamine and compound 48/80 (50, 100, 200, 400 µg/site); two buffered saline injections served as controls. Two blinded investigators reviewed the pruritic behaviours of all video recordings. Global wheal scores were evaluated at 30 min by a blinded investigator. RESULTS: All dogs showed wheal and erythema at the pruritogen injection site; global wheal scores at 30 min of each substance significantly increased at all concentrations compared to control (P ≤ 0.05). A blinded evaluation revealed that all pruritogens induced mild acute pruritic behaviours at the site of injection. There was no injection site pain seen in any dog. Compared to controls, injections of pruritogens did not significantly affect the pruritic seconds or occurrence of pruritic episodes for any of the substances. CONCLUSIONS AND CLINICAL SIGNIFICANCE: These preliminary results suggest that i.d. injections of the studied pruritogens can induce cutaneous wheal and flare response in healthy dogs; but inconsistencies occur in the induction of itch, even with the different concentrations of pruritogens.


Assuntos
Anticorpos Anti-Idiotípicos/administração & dosagem , Eritema/veterinária , Histamina/administração & dosagem , Prurido/veterinária , p-Metoxi-N-metilfenetilamina/administração & dosagem , Animais , Anticorpos Anti-Idiotípicos/efeitos adversos , Cães , Relação Dose-Resposta a Droga , Histamina/efeitos adversos , Injeções Intradérmicas , Masculino , Prurido/induzido quimicamente , Pele/efeitos dos fármacos , p-Metoxi-N-metilfenetilamina/efeitos adversos
6.
Int J Nanomedicine ; 12: 4849-4868, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28744120

RESUMO

BACKGROUND: Type I hypersensitivity is an allergic reaction characterized by the overactivity of the immune system provoked by normally harmless substances. Glucocorticoids, anti-histamines, or mast cell stabilizers are the choices of treatment for type I hypersensitivity. Even though these drugs have the anti-allergic effect, they can have several side effects in prolong use. Cedrol is the main bioactive compound of Cedrus atlantica with anti-tumor, anti-oxidative, and platelet-activating factor inhibiting properties. METHODS: In this study, the preparation and anti-anaphylactic effect of cedrol-loaded nanostructured lipid carriers (NLCs) were evaluated. NLCs were prepared using Compritol® 888 ATO and triolein as lipid phase and vitamin E d-α-tocopherylpolyethyleneglycol 1000 succinate, soya lecithin, and sodium deoxycholate as nanoparticle stabilizers. RESULTS: The average diameter of cedrol-NLCs (CR-NLCs) was 71.2 nm (NLC-C1) and 91.93 nm (NLC-C2). The particle had negative zeta potential values of -31.9 mV (NLC-C1) and -44.5 mV (NLC-C2). Type I anaphylactoid reaction in the animal model is significantly reduced by cedrol and cedrol-NLC. This in vivo activity of cedrol resulted that cedrol suppressed compound 48/80-induced peritoneal mast cell degranulation and histamine release from mast cells. Furthermore, compound 48/80-evoked Ca2+ uptake into mast cells was reduced in a dose-dependent manner by cedrol and cedrol-NLC. Studies confirmed that the inhibition of type I anaphylactoid response in vivo in mice and compound 48/80-induced mast cell activation in vitro are greatly enhanced by the loading of cedrol into the NLCs. The safety of cedrol and CR-NLC was evaluated as selectivity index (SI) with prednisolone and cromolyn sodium as positive control. SI of CR-NLC-C2 was found to be 11.5-fold greater than both prednisolone and cromolyn sodium. CONCLUSION: Administration of CR-NLC 24 hours before the onset of anaphylaxis can prevent an anaphylactoid reaction. NLCs could be a promising vehicle for the oral delivery of cedrol to protect anaphylactic reactions.


Assuntos
Anafilaxia/tratamento farmacológico , Portadores de Fármacos/química , Mastócitos/efeitos dos fármacos , Nanoestruturas/administração & dosagem , Terpenos/administração & dosagem , Administração Oral , Animais , Degranulação Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Portadores de Fármacos/administração & dosagem , Ácidos Graxos , Feminino , Liberação de Histamina/efeitos dos fármacos , Lipídeos/administração & dosagem , Lipídeos/química , Masculino , Mastócitos/fisiologia , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanoestruturas/química , Sesquiterpenos Policíclicos , Terpenos/farmacologia , Trioleína/química , Vitamina E/química , p-Metoxi-N-metilfenetilamina/efeitos adversos
7.
Pharmacol Biochem Behav ; 105: 173-6, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23474370

RESUMO

Although accumulating clinical evidence has shown that psychological stress worsens cutaneous symptoms by exaggerating scratching behavior, how the stress affects the scratching is unclear. Therefore, we herein investigated this using an animal model of scratching. Male BALB/c mice were exposed to 1h water avoidance stress (WAS) for ten consecutive days. Twenty-four hours after the last stress session, the mice were injected into the back of the neck with a condensation product of N-methyl-p- methoxyphenethylamine with formaldehyde (compound 48/80), and their scratching behavior was then observed for 120min. Mast cell number in the skin and histamine and corticosterone levels in the plasma were examined. The scratching number was significantly higher in the chronic WAS group than in the control group. Both mast cell number in the skin and the peak histamine in the plasma after the compound 48/80 injection were also significantly higher in the chronic WAS group in comparison to the control group. Chronic WAS delayed the peak corticosterone plasma response to the compound 48/40 injection. These findings indicate that chronic WAS exacerbates the compound 48/80-induced scratching behavior of mice. Both the increased number of skin mast cells and delayed glucocorticoid reaction may be related to this exacerbation.


Assuntos
Comportamento Animal/efeitos dos fármacos , Prurido/induzido quimicamente , Estresse Psicológico , p-Metoxi-N-metilfenetilamina/efeitos adversos , Animais , Doença Crônica , Camundongos
8.
Int J Mol Med ; 30(2): 344-50, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22614038

RESUMO

Allergic inflammatory disease such as food allergy, asthma and atopic dermatitis are increasing worldwide. In this study, we investigated the effect of water extract of Sparassis crispa (WESC) Fr. (Aphyllophoromycetideae) on mast cell-mediated allergic inflammation and the possible mechanisms of action. WESC inhibited compound 48/80-induced systemic anaphylaxis and serum histamine release in mice. WESC decreased immunoglobulin E (IgE)-mediated passive cutaneous anaphylaxis. Additionally, WESC reduced histamine release and intracellular calcium in human mast cells activated by phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187. WESC decreased PMA and A23187-stimulated expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, inlerleukin (IL)-6 and IL-1ß. The inhibitory effect of WESC on pro-inflammatory cytokines was nuclear factor-κB, extracellular signal-regulated kinase and p38 mitogen-activated protein kinase-dependent. Our results suggest potential therapeutic application of WESC in allergic inflammatory diseases.


Assuntos
Cálcio/metabolismo , Hipersensibilidade/metabolismo , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Polyporales/química , Anafilaxia/induzido quimicamente , Anafilaxia/tratamento farmacológico , Animais , Misturas Complexas/administração & dosagem , Misturas Complexas/farmacologia , Citocinas/metabolismo , Ativação Enzimática/efeitos dos fármacos , Liberação de Histamina/efeitos dos fármacos , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/imunologia , Mediadores da Inflamação/metabolismo , Masculino , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos ICR , Ratos , Ratos Sprague-Dawley , p-Metoxi-N-metilfenetilamina/efeitos adversos
9.
Int J Mol Med ; 29(2): 303-10, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22075758

RESUMO

In this study, we investigated the effect of a water extract of the ripe fruits of Rubus coreanus Miq. (Rosaceae) (RFRC) on mast cell-mediated allergic inflammation and studied the possible mechanism of action. Mast cell-mediated allergic disease is involved in many diseases such as anaphylaxis, rhinitis, asthma and atopic dermatitis. RFRC dose-dependently inhibited compound 48/80-induced systemic anaphylaxis and serum histamine release in mice. RFRC reduced the immunoglobulin E (IgE)-mediated local allergic reaction, passive cutaneous anaphylaxis. RFRC attenuated histamine release from rat peritoneal mast cells and human mast cells by the reduction of intracellular calcium. RFRC decreased the phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore A23187 (PMACI)-stimulated expression and secretion of pro-inflammatory cytokines in human mast cells. The inhibitory effect of RFRC on cytokine production was nuclear factor (NF)-κB- and mitogen-activated protein kinase (MAPK)-dependent. In addition, RFRC suppressed the activation of caspase-1. Our findings provide evidence that RFRC inhibits mast cell-derived allergic inflammatory reactions, and for the involvement of calcium, NF-κB, MAPKs and caspase-1 in these effects. Furthermore, in vivo and in vitro anti-allergic inflammatory effects of RFRC provide affirmative proof of a possible therapeutic application of this agent in allergic inflammatory diseases.


Assuntos
Anafilaxia/imunologia , Frutas/química , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Extratos Vegetais/farmacologia , Rosaceae/química , Anafilaxia/induzido quimicamente , Animais , Cálcio/metabolismo , Caspase 1/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Ativação Enzimática/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Liberação de Histamina/efeitos dos fármacos , Humanos , Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , p-Metoxi-N-metilfenetilamina/efeitos adversos
10.
Eur J Pharmacol ; 670(1): 162-7, 2011 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-21946101

RESUMO

To clarify the mechanisms by which compound 48/80 (C48/80) induces scratching behavior, the involvement of dopamine D(1) receptors was investigated. The intracisternal (i.t.) administration of SCH23390 (1.0 µg), a selective dopamine D(1) receptor antagonist, significantly decreased C48/80-induced scratching behavior in mice. These results suggest that dopamine D(1) receptors contribute to scratching behavior or the itch sensation induced by subcutaneous injection of C48/80 in mice. Co-administration of SCH23390 and C48/80 enhanced c-fos immunoreactivities in the peduncular part of the lateral hypothalamus (PLH), whereas the immunoreactivities in the other groups were unchanged. The dopaminergic system may be playing an important role in the suppression of C48/80-induced scratching behavior by SCH23390.


Assuntos
Antipruriginosos/farmacologia , Comportamento Animal/efeitos dos fármacos , Benzazepinas/farmacologia , Receptores de Dopamina D1/antagonistas & inibidores , p-Metoxi-N-metilfenetilamina/efeitos adversos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Transporte Proteico/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , p-Metoxi-N-metilfenetilamina/administração & dosagem
11.
Int Immunopharmacol ; 11(8): 1052-6, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21382532

RESUMO

Mast cells stimulation activates degranulation process resulting in releasing of mediators, such as histamine. In this study, the effect of aqueous extract of sitagliptin, a selective dipeptidylpeptidase-4 inhibitor, on the mast cell-mediated allergic response was studied with the possible mechanisms of action, focusing on the histamine release and pro-inflammatory cytokine secretion in mast cells. Sitagliptin produced dose dependent inhibition in compound 48/80-induced systemic reactions. In addition, sitagliptin attenuated IgE-mediated skin allergic reaction. Sitagliptin dose-dependently reduced compound 48/80- and IgE-induced histamine release from mast cells. Sitagliptin decreased the secretion of pro-inflammatory cytokines, tumor necrosis factor-α, in mast cells. So, the finding of this study provides evidence that sitagliptin inhibits mast cell derived allergic reactions, and involvement of pro-inflammatory cytokine secretion in such effects.


Assuntos
Anafilaxia/tratamento farmacológico , Hipersensibilidade/tratamento farmacológico , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Pirazinas/farmacologia , Triazóis/farmacologia , Anafilaxia/induzido quimicamente , Anafilaxia/imunologia , Anafilaxia/metabolismo , Animais , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Liberação de Histamina/efeitos dos fármacos , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Masculino , Camundongos , Ovalbumina/farmacologia , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Anafilaxia Cutânea Passiva/imunologia , Pirazinas/química , Ratos , Ratos Wistar , Fosfato de Sitagliptina , Triazóis/química , Fator de Necrose Tumoral alfa/metabolismo , p-Metoxi-N-metilfenetilamina/efeitos adversos , p-Metoxi-N-metilfenetilamina/farmacologia
12.
Int Immunopharmacol ; 10(9): 1135-41, 2010 09.
Artigo em Inglês | MEDLINE | ID: mdl-20620227

RESUMO

Chlorogenic acid (CGA), a naturally occurring polyphenol compound, has a number of biological activities. However, roles of CGA in the mast cell-dependent anaphylactic reaction have not been fully examined. In the present study, the effect and mechanism of CGA on mast cell-dependent anaphylactic reaction were investigated using in vivo and in vitro models. CGA inhibited compound 48/80-induced systemic anaphylactic shock in mice and skin vascular permeability in rats. CGA also inhibited anti-dinitrophenyl (DNP) IgE-mediated passive cutaneous anaphylaxis (PCA). Moreover, CGA dose-dependently reduced histamine and TNF-alpha release from RBL-2H3 cells activated by anti-DNP IgE. Pretreatment with CGA suppressed IgE-antigen complex induced calcium uptake into RBL-2H3 cells. When CGA was added, the level of intracellular cyclic adenosine monophosphate (cAMP) in RBL-2H3 cells was significantly elevated compared with the untreated cells. Decreased calcium uptake and increased cAMP level might be involved in the inhibitory effect of CGA on mast cell activation. These results suggest a possible therapeutic application of CGA in allergic diseases.


Assuntos
Anafilaxia/tratamento farmacológico , Ácido Clorogênico/farmacologia , Mastócitos/efeitos dos fármacos , Anafilaxia/induzido quimicamente , Anafilaxia/imunologia , Animais , Cálcio/análise , Cálcio/imunologia , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/imunologia , Permeabilidade Capilar/efeitos dos fármacos , Permeabilidade Capilar/imunologia , Células Cultivadas , Ácido Clorogênico/uso terapêutico , AMP Cíclico/análise , AMP Cíclico/imunologia , Dinitrofenóis/toxicidade , Liberação de Histamina/efeitos dos fármacos , Liberação de Histamina/imunologia , Imunoglobulina E/análise , Imunoglobulina E/imunologia , Masculino , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Pele/imunologia , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , p-Metoxi-N-metilfenetilamina/efeitos adversos , p-Metoxi-N-metilfenetilamina/imunologia
13.
Food Chem Toxicol ; 45(11): 2138-44, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17602813

RESUMO

The mast cell-mediated immediate-type allergic reaction is involved in many allergic diseases such as asthma, allergic rhinitis and sinusitis. Stimulation of mast cells starts the process of degranulation resulting in release of mediators such as histamine and an array of inflammatory cytokines. In this report, we investigated the effect of aqueous extract of Amomum xanthiodes (Zingiberaceae) (AXE) on the mast cell-mediated allergy model and studied its possible mechanisms of action. AXE inhibited compound 48/80-induced systemic reactions and serum histamine release in mice. AXE decreased immunoglobulin E (IgE)-mediated passive cutaneous anaphylaxis reaction. AXE reduced histamine release and intracellular calcium from rat peritoneal mast cells activated by compound 48/80. Furthermore, AXE decreased the activation of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase and c-jun N-terminal kinase, and downstream tumor necrosis factor (TNF)-alpha production in phorbol 12-myristate 13-acetate and calcium ionophore A23187-stimulated human mast cells. Our findings provide evidence that AXE inhibits mast cell-derived allergic reactions, and that intracellular calcium, TNF-alpha, and p38 MAPK are involved in these effects.


Assuntos
Amomum/química , Hipersensibilidade/tratamento farmacológico , Mastócitos/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Animais , Antialérgicos/química , Antialérgicos/uso terapêutico , Calcimicina , Células Cultivadas , Relação Dose-Resposta a Droga , Histamina , Masculino , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Ésteres de Forbol , Fitoterapia , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , p-Metoxi-N-metilfenetilamina/efeitos adversos , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
14.
Arch Pharm Res ; 29(9): 752-6, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17024848

RESUMO

Artemisia princeps Pampanini, which is called Ssajuarissuk in Korean (SS-1), was fermented with lactic acid bacteria (LAB) and their passive cutaneous anaphylaxis reaction-inhibitory activity was investigated. Of these fermented agents, SS-1 extract fermented with Bifidobacterium infantis K-525 (F-SS-1) most effectively inhibited the release of P-hexosamindase from RBL-2H3 cells induced IgE. In IgE-induced RBL-2H3 cells, F-SS-1 inhibited proinflammatory cytokines IL-6 and TNF-alpha mRNA expression. Oral administration of SS-1 and F-SS-1 to mice inhibited passive cutaneous anaphylaxis (PCA) reaction induced by IgE and scratching behaviors induced by compound 48/80. The inhibitory activity of F-SS-1 against scratching behaviors was more effective than that of SS-1. These findings suggest that the fermentation of SS-1 with LAB can increase its antiallergic activity.


Assuntos
Antialérgicos/farmacologia , Artemisia/química , Bactérias/metabolismo , Ácido Láctico/metabolismo , Animais , Linhagem Celular , Fezes/microbiologia , Feminino , Fermentação , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Anafilaxia Cutânea Passiva , Extratos Vegetais/farmacologia , Prurido/induzido quimicamente , Prurido/tratamento farmacológico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , beta-N-Acetil-Hexosaminidases/metabolismo , p-Metoxi-N-metilfenetilamina/efeitos adversos
16.
Int Arch Allergy Immunol ; 139(1): 31-7, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16272824

RESUMO

BACKGROUND: Mast cells are key effector cells in the early-phase allergic inflammation and in diverse immunological and pathological processes. Sopoongsan (SPS), a traditional Korean medicine, has been used as therapeutics for allergic diseases such as atopic dermatitis (AD). The precise effect in experimental models of SPS, however, remains unknown. In this report, we investigated the effect of SPS on mast cell-mediated anaphylactic reactions and cytokine production in in vivo and in vitro murine models. METHODS: Compound 48/80-induced histamine and ear swelling were measured with the various concentrations of SPS. The amount of dye was determined colorimetrically after antidinitrophenyl IgE antibody-induced passive cutaneous anaphylaxis reaction. Secretion of tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) and IL-6 in supernatants from HMC-1 cells was measured by a sandwich enzyme-linked immunosorbent assay. The expression level of nuclear factor (NF)-kappaB/Rel A in the nucleus and the activation of mitogen-activated protein kinases (MAPKs) were examined by Western blot analysis. RESULTS: SPS inhibited the degranulation and histamine release from the rat peritoneal mast cells activated by compound 48/80. Compound 48/80-induced ear swelling was significantly reduced. SPS also showed an inhibitory effect of passive cutaneous anaphylaxis reaction. Significantly reduced levels (p < 0.05) of TNF-alpha, IL-8 and IL-6 were observed in the human mast cell line with SPS and SPS components. In addition, SPS inhibited an increase of NF-kappaB and extracellular signal-regulated kinase 1/2 activity. CONCLUSIONS: These findings suggest that SPS has an inhibitory effect on atopic allergic reaction and this might be useful for the clinical application to treat allergic diseases such as AD.


Assuntos
Antialérgicos/farmacologia , Dermatite Atópica/tratamento farmacológico , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Administração Oral , Animais , Antialérgicos/administração & dosagem , Antialérgicos/uso terapêutico , Citocinas/biossíntese , Dermatite Atópica/induzido quimicamente , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Histamina/análise , Histamina/metabolismo , Humanos , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Anafilaxia Cutânea Passiva/imunologia , Extratos Vegetais/administração & dosagem , Ratos , p-Metoxi-N-metilfenetilamina/efeitos adversos
17.
J Ethnopharmacol ; 98(3): 361-5, 2005 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-15814273

RESUMO

We investigated the effect of a herbal formulation Okbyungpoong-Gamhmi (OG) on mast cell-dependent anaphylactic reactions by intra-rectal administration. OG concentration dependently inhibited compound 48/80-induced anaphylaxis-like response and ear swelling response with doses of 0.01-1g/kg. OG also inhibited the passive cutaneous anaphylaxis at the same concentrations. The histamine release induced by compound 48/80 or IgE from the rat peritoneal mast cells was reduced by 64.2 and 63.6%, respectively, at 1g/l. These results provide evidence that intra-rectal therapy of OG may be beneficial in the treatment of anaphylactic response.


Assuntos
Anafilaxia/tratamento farmacológico , Mastócitos/efeitos dos fármacos , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Fitoterapia/métodos , Preparações de Plantas/uso terapêutico , p-Metoxi-N-metilfenetilamina/antagonistas & inibidores , Anafilaxia/induzido quimicamente , Animais , Coreia (Geográfico) , Masculino , Mastócitos/metabolismo , Medicina Tradicional , Camundongos , Camundongos Endogâmicos ICR , Preparações de Plantas/isolamento & purificação , Ratos , Ratos Sprague-Dawley , p-Metoxi-N-metilfenetilamina/efeitos adversos
18.
J Pharmacol Toxicol Methods ; 49(1): 31-7, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-14670692

RESUMO

INTRODUCTION: Many therapeutic agents stimulate histamine release from mast cells, which results in a decrease in blood pressure. The purpose of this study is to establish a method to determine if the mechanism of action, or one of the mechanisms, of hypotensive compounds is related to the release of histamine. The method was developed using a novel hypotensive compound, SC-372. METHODS: In Inactin anesthetized rats, after intravenous administration of SC-372 (0.3-7 mg/kg), the 2 and 7 mg/kg resulted in a dose-dependent decrease in blood pressure. Histamine (0.1 and 1 mg/kg) was injected intravenously to establish whether histamine release was the mechanism of action for the hypotension induced by SC-372. Compound 48/80 (0.1 mg/kg, promotes histamine release) and Cromolyn (1 mg/kg/min, [5 min], prevents histamine release from mast cells) were characterized and used intravenously in combination with/or compared to SC-372. RESULTS: Histamine resulted in a decrease in blood pressure that was unaffected by Cromolyn (1 mg/kg). Administration of Compound 48/80 resulted in a rapid reduction of systemic blood pressure. Intravenous infusion of Cromolyn prior to the injection of Compound 48/80 significantly attentuated the hypotensive response and the increase in histamine levels in the plasma. Intravenous administration of SC-372 resulted in a rapid reduction in blood pressure with a profile similar to that of Compound 48/80. When the rats were treated with Cromolyn prior to the administration of SC-372, both the blood pressure and plasma histamine levels were maintained at their pretreatment control levels. DISCUSSION: These data indicate that Compound 48/80 and Cromolyn can be used in rats to screen for histamine release-dependent drug-induced hypotension and suggest that the rapid decrease in blood pressure caused by SC-372 may result from histamine release from mast cells.


Assuntos
Guanidinas/efeitos adversos , Liberação de Histamina/efeitos dos fármacos , Hipotensão/induzido quimicamente , Pirazinas/efeitos adversos , Animais , Cromolina Sódica/efeitos adversos , Cromolina Sódica/farmacologia , Guanidinas/farmacologia , Hipotensão/fisiopatologia , Injeções Intravenosas , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Pirazinas/farmacologia , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , p-Metoxi-N-metilfenetilamina/efeitos adversos , p-Metoxi-N-metilfenetilamina/farmacologia
19.
Pain ; 102(1-2): 179-86, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12620609

RESUMO

The local, peripheral administration of antidepressants and excitatory amino acid receptor antagonists can cause analgesia in a number of conditions. The present study examined the effects of combinations of dextromethorphan and ketamine, two clinically used N-methyl-D-aspartate (NMDA) receptor antagonists, with amitriptyline on formalin-evoked behaviors and paw edema. Pretreatment with amitriptyline or dextromethorphan (10-300 nmol) resulted in suppression of flinching behaviors induced by 2.5% formalin, but ketamine had no intrinsic effect. Combination of an inactive dose of dextromethorphan with amitriptyline, and vice versa, resulted in an increase of analgesia so that previously inactive doses now caused significant analgesia. Combinations of multiple doses of ketamine with amitriptyline did not modify the response to amitriptyline. Both dextromethorphan and ketamine increased the paw edema induced by formalin, and this was blocked by low doses of amitriptyline. In the absence of formalin, amitriptyline (1-100 nmol) caused a dose-related suppression of the paw edema produced by dextromethorphan and ketamine. Amitriptyline also blocked paw edema produced by 5-hydroxytryptamine and compound 48/80. Each of the drugs used in this study exerts multiple pharmacological effects. Increased analgesia by drug combinations (amitriptyline/dextromethorphan) could show the involvement of a number of these mechanisms (e.g. NMDA receptor blockade, blockage of sodium channels, blockage of biogenic amine receptors), while a lack of intensification (amitriptyline/ketamine) could reflect occluded actions due to expression of similar actions by the other drug. Paw edema induced by dextromethorphan and ketamine involves inhibition of biogenic amine reuptake, and the ability of amitriptyline to block biogenic amine receptors likely accounts for its inhibiton of these actions. Combinations of these particular agents could represent a method for augmented analgesia and minimization of local adverse reactions.


Assuntos
Amitriptilina/uso terapêutico , Analgésicos não Narcóticos/uso terapêutico , Dextrometorfano/uso terapêutico , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Ketamina/uso terapêutico , Dor/tratamento farmacológico , Amitriptilina/administração & dosagem , Analgésicos não Narcóticos/administração & dosagem , Animais , Comportamento Animal/efeitos dos fármacos , Dextrometorfano/administração & dosagem , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Edema/induzido quimicamente , Edema/tratamento farmacológico , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Formaldeído/efeitos adversos , Membro Posterior , Histamina/efeitos adversos , Injeções Subcutâneas , Ketamina/administração & dosagem , Masculino , Dor/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Serotonina/efeitos adversos , Agonistas do Receptor de Serotonina/efeitos adversos , Fatores de Tempo , p-Metoxi-N-metilfenetilamina/efeitos adversos
20.
Clin Chim Acta ; 312(1-2): 163-8, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11580922

RESUMO

BACKGROUND: Mast cells synthesize and secrete chemical mediators which play a central role in anaphylaxis. METHODS: The effect of Acanthopanax senticosus root (ASR) on mast cell-dependent anaphylaxis was investigated. RESULTS: ASR inhibited compound 48/80-induced systemic anaphylactic shock at the dose of 1.0 g/kg by 50%. When ASR was given as pre-treatment at concentrations ranging from 0.01 to 2.0 g/l, the histamine release from rat peritoneal mast cells induced by compound 48/80 was reduced in a dose-dependent manner. ASR (2.0 g/kg) also inhibited passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE to 53.17+/-6.62%. Moreover, ASR inhibited tumor necrosis factor-alpha production in a concentration-dependent manner, and the treatment of 1 g/l blocked the production by 32.5+/-3.50% compared to saline value. CONCLUSIONS: ASR may possess effective anti-anaphylactic activity.


Assuntos
Anafilaxia/tratamento farmacológico , Mastócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Anafilaxia/induzido quimicamente , Anafilaxia/patologia , Animais , Células Cultivadas , Dinitrobenzenos/imunologia , Histamina/metabolismo , Imunoglobulina E/farmacologia , Masculino , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Raízes de Plantas/química , Plantas Medicinais , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , p-Metoxi-N-metilfenetilamina/efeitos adversos
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