Mast cells and histamine play an important role in edema and leukocyte recruitment induced by Potamotrygon motoro stingray venom in mice.

This work aimed to investigate mechanisms underlying the inflammatory response caused by Potamotrygon motoro stingray venom (PmV) in mouse paws. Pre-treatment of animals with a mast cell degranulation inhibitor (cromolyn) diminished edema (62% of inhibition) and leukocyte influx into the site of PmV injection. Promethazine (histamine type 1 receptor antagonist) or thioperamide (histamine type 3 and 4 receptor antagonist) also decreased edema (up to 30%) and leukocyte numbers, mainly neutrophils (40-50 %). Cimetidine (histamine type 2 receptor antagonist) had no effect on PmV-induced inflammation. In the RBL-2H3 lineage of mast cells, PmV caused proper cell activation, in a dose-dependent manner, with release of PGD2 and PGE2. In addition, the role of COXs products on PmV inflammatory response was evaluated. Indomethacin (COX-1/COX-2 inhibitor) or etoricoxib (COX-2 inhibitor) partially diminished edema (around 20%) in PmV-injected mice. Indomethacin, but not etoricoxib, modulated neutrophil influx into the site of venom injection. In conclusion, mast cell degranulation and histamine, besides COXs products, play an important role in PmV-induced reaction. Since PmV mechanism of action remains unknown, hindering accurate treatment, clinical studies can be performed to validate the prescription of antihistaminic drugs, besides NSAIDs, to patients injured by freshwater stingrays.

Importância do teor de histamina sobre a qualidade do pescado / Importance of histamine content about the quality of fish

o Brasil possui papel representativo na produção e exportação de pescado. O pescado caracteriza-se por ser um alimento bastante nutritivo e saudável e também por ser altamente perecível. Para um produto ser de boa qualidade tem que haver um controle adequado para prevenir enfermidades através de seu consumo. Dentre estas se destaca a doença provocada pela histamina que ocorre através da descarboxilação da histidina. Além de riscos à saúde humana com a intoxicação, peixes com violações no teor de histamina não são importados pela União Européia. Por isso, deve-se fazer uma análise de maneira rápida e eficaz nos lotes das indústrias. O objetivo do presente trabalho foi destacar a importância da histamina na qualidade do pescado através da revisão bibliográfica. Com esse trabalho pode-se concluir que a histamina é formada por diversos fatores e sua presença alta geralmente indica falhas higienicossanitárias, principalmente pelo binômio tempo/temperatura em alguma parte do processamento. (AU)

Fish is a highly nutritious food and very important for the human diet. However, it is very perishable and for a good quality product has to be a great control to prevent infections through it. Among the infections can highlight that caused by histamine, which occurs through the decarboxylation of histidine. In addition the risks to human health with intoxication fish with high level of histamine are not imported by European Community. Because of it you should do an analysis quickly and effectively in lots of industries. The aim of this study was to highlight the importance of histamine in fish quality through the literature review. With this work can be seen that histamine is formed by several factors and their presence usually indicates high hygienic and sanitary failures, especially for time / temperature somewhere in the processing. (AU)

Effects of babassu nut oil on ischemia/reperfusion-induced leukocyte adhesion and macromolecular leakage in the microcirculation: observation in the hamster cheek pouch.

BACKGROUND: The babassu palm tree is native to Brazil and is most densely distributed in the Cocais region of the state of Maranhão, in northeastern Brazil. In addition to the industrial use of refined babassu oil, the milk, the unrefined oil and the nuts in natura are used by families from several communities of African descendants as one of the principal sources of food energy. The objective of this study was to evaluate the effects of babassu oil on microvascular permeability and leukocyte-endothelial interactions induced by ischemia/reperfusion using the hamster cheek pouch microcirculation as experimental model. METHODS: Twice a day for 14 days, male hamsters received unrefined babassu oil (0.02 ml/dose [BO-2 group], 0.06 ml/dose [BO-6 group], 0.18 ml/dose [BO-18 group]) or mineral oil (0.18 ml/dose [MO group]). Observations were made in the cheek pouch and macromolecular permeability increase induced by ischemia/reperfusion (I/R) or topical application of histamine, as well as leukocyte-endothelial interaction after I/R were evaluated. RESULTS: The mean value of I/R-induced microvascular leakage, determined during reperfusion, was significantly lower in the BO-6 and BO-18 groups than in the MO one (P < 0.001). In addition, histamine-induced increase of microvascular permeability was significantly less pronounced in BO groups compared to MO one. No significant differences among groups in terms of leukocyte adhesion, concentrations of tumor necrosis factor alpha, interleukin 1, and interleukin 6 were found. CONCLUSIONS: Our findings suggest that unrefined babassu oil reduced microvascular leakage and protected against histamine-induced effects in postcapillary venules and highlights that these almost unexploited nut and its oil might be secure sources of food energy.

Emotional memory consolidation impairment induced by histamine is mediated by H1 but not H2 receptors.

Histaminergic fibers are present in the molecular and granular layers of the cerebellum and have high density in the vermis and flocculus. Evidence indicates that the cerebellar vermis is involved in memory consolidation. Recently, we demonstrated that when histamine is microinjected into the cerebellar vermis it results in impaired emotional memory consolidation in mice that are submitted to the elevated plus maze (EPM). This study investigated whether histamine impairment was mediated by the H(1) or H(2) receptors. The cerebellar vermis of male mice (Swiss Albino) were implanted using a guide cannula. Three days after recovery, behavioral tests were performed in the EPM on two consecutive days (Trial 1 and Trial 2). Immediately after exposure to the EPM (Trial 1), animals received a microinjection of histaminergic drugs. In Experiment 1, saline (SAL) or histamine (HA, 4.07 nmol/0.1 µl) was microinjected 5 min after pretreatment with the H(1) antagonist chlorpheniramine (CPA, 0.16 nmol/0.1µl) or SAL. In Experiment 2, SAL or HA was microinjected into the mice 5 min after pretreatment with the H(2) antagonist ranitidine (RA, 2.85 nmol/0.1 µl) or SAL. Twenty-four hours later, the mice were re-exposed to the EPM (Trial 2) under the same experimental conditions but did not receive an injection. On both days, the test sessions were recorded to enable analysis of the behavioral measures. The decrease in open arm exploration (% entries and % time spent in the open arms) in Trial 2 relative to Trial 1 was used as a measure of learning and memory. The data were analyzed using the two-way analysis of variance (ANOVA) and Duncan's tests. In Experiment 1, the Duncan's test indicated that the mice entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in Trial 2 after being microinjected with SAL+SAL, SAL+CPA and CPA+HA. However, the animals that received SAL+HA did not enter the open arms less frequently or spend less time in them, which was significantly different from the CPA+HA group. The results of Experiment 2 demonstrated that the %OAE and %OAT in Trial 2 were different from Trial 1 for the groups that were microinjected with SAL+SAL and SAL+RA. The animals that were microinjected with RA+HA or with SAL+HA did not show a reduction in %OAE. These results demonstrate that the animals treated with HA did not avoid the open arms less on retesting and indicated that CPA did not alter the behavior parameters but did revert the histamine-induced impairment of memory consolidation. Furthermore, the H(2) antagonist RA, at the dose used in this study, did not affect memory consolidation and failed to revert histamine-induced impairment.

Anti-inflammatory evaluation of Solidago chilensis Meyen in a murine model of pleurisy.

UNLABELLED: The aim of this study was to investigate the anti-inflammatory effects and the mechanism of action of the aqueous extracts obtained from rhizomes, leaves and inflorescences of Solidago chilensis in the mouse model of pleurisy. The extracts were prepared by infusion and were lyophilized. RESULTS: The aqueous extracts of rhizomes, leaves or inflorescences inhibited leukocytes, neutrophils and exudation (P<0.05) in the inflammation induced by carrageenan. The rhizomes aqueous extract, butanolic and aqueous residual fractions inhibited leukocytes, neutrophils, myeloperoxidase, adenosine-deaminase, and tumor necrosis factor alpha levels in the inflammation induced by carrageenan (P<0.05). The rhizome aqueous extract and butanolic fraction also inhibited exudation, nitric oxide, and interleukin-1 beta levels (P<0.05). The rhizomes aqueous extract and its two derived fractions reduced leukocytes and mononuclears in the pleurisy induced by bradykinin, histamine, or substance P (P<0.05) and neutrophils in the pleurisy induced by histamine or substance P (P<0.05). Only aqueous residual fraction inhibited neutrophils induced by bradykinin (P<0.05). CONCLUSION: Solidago chilensis aqueous extracts from leaves, inflorescences and rhizomes demonstrated an important anti-inflammatory effect, inhibiting cells in the inflammation caused by carrageenan. In addition, the rhizomes aqueous extract and its derived fractions also decreased pro-inflammatory mediators release into the site of the inflammatory process. The rhizomes aqueous extract and the butanolic fraction showed more evident anti-inflammatory actions.

Antioedematogenic effect of marrubiin obtained from Marrubium vulgare.

This paper describes the antioedematogenic profile of marrubiin (1), the main constituent of Marrubium vulgare, a medicinal plant used in folk medicine of several countries to treat different pathologies. Compound (1) was analyzed in a model of microvascular leakage in mice ears. The results show that it exhibits significant and dose-related antioedematogenic effects. The results obtained for ID50 values (mg/kg, i.p.) and maximal inhibition (%) for the different phlogistic agents used were as follows: histamine (HIS, 13.84 mg/kg and 73.7%); (BK, 18.82 mg/kg and 70.0%); carrageenan (CAR, 13.61 mg/kg and 63.0%). The other phlogistic agonists, such as prostaglandin E2 (PGE2), caused inhibition of less than 50%. In addition, (1) (100 mg/kg) significantly inhibited the OVO-induced allergic edema in actively sensitized animals (maximal inhibition 67.6+/-4%). Our results demonstrate that the systemic administration of marrubiin exerts a non-specific inhibitory effect on pro-inflammatory agent-induced microvascular extravasation of Evans blue in mouse ear.

Antiinflammatory effects of Tacrolimus in a mouse model of pleurisy.

INTRODUCTION: Tacrolimus is an antibiotic macrolide with immunosuppressant properties isolated from Streptomyces tsukubaensis. OBJECTIVES: This study evaluated whether the acute and systemic administration of Tacrolimus significantly interfered in leukocyte migration, exudation, myeloperoxidase and adenosine-deaminase and nitric oxide levels, as well as Interleukin-1 (IL-1beta) and tumor necrosis factor alpha (TNFalpha) levels in a mouse model of pleurisy in comparison to those obtained with dexamethasone. MATERIALS AND METHODS: Pleurisy was induced by carrageenan (Cg, 1%), bradykinin (BK, 10 nmol), histamine (HIS, 1 micromol) or substance P (PS, 20 nmol) administered by intrapleural route (ipl.) and the inflammatory parameters (cell migration and exudation) were analyzed 4 h after. In the model of pleurisy induced by carrageenan, other markers in the pleural fluid, such as cytokines (TNFalpha and Il-1beta), nitrite/nitrate (NOx), myeloperoxidase (MPO) and adenosine-deaminase (ADA) levels, were also studied. Dexamethaseone (0.5 mg/kg, i.p., 0.5 h before) was also analyzed in all protocols. RESULTS: In the pleurisy induced by carrageenan, Tacrolimus (1 mg/kg, i.p.) and dexamethasone (0.5 mg/kg, i.p.) administered 0.5 h before caused a significant decrease in leukocytes, neutrophils and exudation (P < 0.01). Under the same conditions, Tacrolimus and dexamethasone did not modify the blood's white or red cells (P > 0.05). Tacrolimus showed a long lasting antiinflammatory effect, inhibiting leukocytes and neutrophils for up to 24 h (P < 0.01), whereas the inhibition of exudation was less marked (up to 2 h) (P < 0.01). These drugs caused a marked reduction in MPO activity, as well as IL-1beta and TNFalpha levels (P < 0.01), but only Tacrolimus inhibited ADA activity (P < 0.01). On the other hand, dexamethasone, but not Tacrolimus, inhibited NOx levels (P < 0.01). In the same conditions, Tacrolimus significantly inhibited cell migration induced by either bradykinin, histamine or substance P (P < 0.05). In a similar manner, dexamethasone inhibited leukocyte influx induced by bradykinin and histamine (P < 0.05). Regarding exudation effects, dexamethasone markedly inhibited this parameter induced by BK, HIS or SP, whereas Tacrolimus only inhibited exudation caused by HIS (P < 0.05). CONCLUSIONS: The results of the present work indicate that Tacrolimus showed important antiinflammatory properties against pleurisy in mice that are different from those caused by dexamethasone. The inhibition of proinflammatory cytokine (TNFalpha, IL-1beta), enzyme (myeloperoxidase, adenosine-deaminase) and mediator (bradykinin, histamine, substance P) release and/or action appears to account for Tacrolimus's actions.

Pleural fluid eosinophils suppress local IgE-mediated protein exudation in rats.

Eosinophils are supposed to play a critical role in the pathology of several allergic diseases because after activation they can release toxic and proinflammatory agents. In this study we have investigated whether IgE-mediated rat pleurisy could be affected by an ongoing pleural eosinophilic inflammatory response. IgE-passively sensitized rats were challenged with an intrapleural (i.pl.) injection of allergen (dinitrophenylated bovine serum albumin, 1 microgram/cavity) and exudation assessed by measuring the amount of protein extravasated into the pleural cavity within 4 h. We have confirmed that lipopolysaccharide (LPS) stimulation (250 ng/cavity i.pl.) was followed by a marked pleural neutrophilia, apparent at 3 h, which was followed by an eosinophil accumulation noted within 48-72 h postchallenge. We have also confirmed that a boiled sample of LPS pleural washing (LPS-PW, 200 microliters i.pl.) caused selective eosinophilia in recipient rats. Pleural exudation remained unaltered when the allergenic challenge was performed 3 h after LPS in a condition of intense pleural fluid neutrophilia. In contrast, this was significantly reduced (P < .001) when the challenge occurred 72 h after LPS or 24 h after LPS-PW in selective pleural fluid eosinophilia. In another series of experiments repeated daily i.pl. injections of platelet-activating factor (PAF; 1 microgram/cavity) resulted in a progressive increase in eosinophil number recovered from the pleural cavity. The values were 1.2 +/- 0.2, 3.0 +/- 0.2, and 5.8 +/- 0.5 x 10(6) eosinophils/cavity (mean +/- SEM) after 0, 1, and 4 injections, respectively. Allergen challenge performed after 0, 1, or 4 PAF stimulations led to pleural protein levels of 88.6 +/- 5.7, 33.7 +/- 0.7, and 19.4 +/- 2.3 mg/cavity, respectively, indicating that the allergic pleurisy is inhibited in a manner dependent on the magnitude of eosinophil accumulation. Furthermore, the impairment of PAF-induced eosinophil accumulation by cetirizine (30 mg/kg i.p.) restored the exudatory response. Exudation triggered by compound 48/80 (25 micrograms/cavity), histamine (200 micrograms/cavity), or 5-hydroxytryptamine (100 micrograms/cavity) was not affected by four previous PAF daily injections. The findings indicate that allergen-induced exudation is selectively down-regulated in the eosinophil-enriched pleural space of rats, a suppression that increased with increasing eosinophil number and disappeared after chemical impairment of the eosinophilia.