Inhibition of inducible nitric oxide synthase-derived nitric oxide as a therapeutical target for acute pancreatitis induced by secretory phospholipase A(2)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Alkyl Caffeates as Anti-Helicobacter Pylori and Scavenger of Oxidants Produced by Neutrophils

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antiplatelet drugs reduce the immunoinflammatory response in a rat model of periodontal disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of Parstatin on Experimental Periodontal Disease and Repair in Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação da influência do estresse em modelo experimental de colite por administração de Ácido Trinitrobenzenosulfônico (TNBS) em concentração subinflamatória

Inflammatory bowel disease (IBD) is a chronic and relapsing disease caused by exaggerated response of the immune system. It represents a significant health problem by limiting the quality of life and being the main risk factor for colorectal cancer. Despite of its importance, the high worldwide incidence and being the object of research for several decades, the etiology remains unknown. Studies indicates an interaction between genetic and environmental factors which together with the intestinal microbiota, leads to an uncontrolled immune response. One of the aggravating environmental factors often discussed is stress, as the daily life of the population in general is increasingly rushed. In order to demonstrate the influence of stress on IBD, this study aimed to standardize an experimental model of colitis induced by instillation of a trinitrobenzene sulfonic acid (TNBS) noninflammatory concentration plus exposure to stress that intensify the inflammation. Therefore, an experiment was done to determine what would be the noninflammatory concentration. In this step, four different concentrations of TNBS (1, 6, 12.5 or 40mg/ml) were tested and the lowest concentration capable of inducing a noninflammatory response in the gut was defined as 1 mg/ml. Then, a second experiment was performed which induced colitis and exposed the animals to restraint stress. The results, however, showed that this stimulus was not enough to exacerbate the damage caused by the 1 mg/ml concentration of TNBS in the colon. With some changes in the protocol, the third experiment associated cold and restraint, as well as changes on the day of euthanasia, which occurred immediately after the stress session. The results of myeloperoxidase activity measurement were unexpected due to the noninflammatory concentration of TNBS caused an intestinal inflammation similar to the concentration of 40 mg/ml. However, the results of glutathione quantification and the corticosterone ...

Avaliação das propriedades antioxidantes da Curcumina em sistemas-modelo in vitro

A curcumina, um pigmento natural extraído do rizoma da Curcuma longa L. é utilizada em alimentos, principalmente aqueles condimentados com curry e açafrão. Vários estudos demonstram seu efeito benéfico em diversas doenças, tais como: diabetes, hepatopatias, câncer, entre outras. Uma de suas propriedades é a atividade antioxidante, pois em pequenas quantidades é capaz de inibir ou retardar processos oxidativos. Para substanciar o estudo desta propriedade, comparou-se a capacidade de captura de espécies reativas radicalares e não radicalares pela curcumina, com padrões (biomoléculas, exceto o trolox) antioxidantes: ascorbato, crocina, glutationa, quercetina, rutina, trolox e urato, em sistemas-modelo in vitro, sobre a captura dos radicais: 2-2'-azino-bis (3-etilbenzotiazolina-6-ácido sulfônico) (ABTS●+ ); 2,2-difenil-1 picril-hidrazila (DPPH● ); ânion radical superóxido (O2 ●-); HOCl/OCl- e H2O2. Investigou-se também seu efeito inibitório na geração do HOCl no sistema, mieloperoxidase (MPO)/H2O2/Cl- (via clorinante) e na inibição da oxidação do guaiacol MPO/H2O2/Guaiacol (via peroxidativa). A curcumina nos ensaios com ABTS●+ ou O2 ●-, apresentou o 3° menor IC50, 4,93 e 99,66 µmol/L, respectivamente; com o DPPH● apresentou o 6° menor IC50, 24,70 µmol/L; com o HOCl/OCl- apresentou o menor IC50, 1,12µmol/L e no ensaio com o H2O2 não atingiu o IC50. No ensaio com o sistema MPO/H2O2/Cl-, observou-se alteração da banda de absorção (bleaching) da curcumina (420 nm), além disso, nos ensaios com a via clorinante (MPO/H2O2/Cl-) e revelados com 3, 3’, 5, 5’- tetrametilbenzidina (TMB) e iodeto de potássio em meio ácido, observou-se aumento da absorbância (650 nm), o que impossibilitou o estudo de sua inibição nesta via. Entretanto, na via peroxidativa, observou-se uma diminuição significativa da absorbância do produto de oxidação... (Resumo completo, clicar acesso eletrônico abaixo)

Apocinina versus diapocinina como inibidor da produção de peróxido de hidrogênio e ácido hipocloroso por neutrófilos ativados

Apocynin has been used as an efficient inhibitor of the multi-enzymatic complex NADPH oxidase in many experimental models involving phagocytic and nonphagocytic cells. The mechanism of inhibition has been linked with the previous activation of apocynin through the action of cellular peroxidases leading to the formation of a dimeric oxidation product, diapocynin. In this study we compared apocynin with pure diapocynin regarding their effects as scavenger of hydrogen peroxide and hypochlorous generated by glucose/glucose oxidase and myeloperoxidase respectively, and as inhibitors of the production of hydrogen peroxide and hypochlorous acid by activated neutrophils. The production of hydrogen peroxide was measured by the oxidation of the fluorescent substance Amplex Red and the production of hypochlorous acid by was measured as taurine-chloramine derivative using the chromogenic substrate 3,3’,5,5’- tetramethylbenzidine (TMB). Neutrophils (1 x106 cells/mL) were pre-incubated in PBS buffer supplemented with 1 mM calcium chloride, 0.5 mM magnesium chloride, 1 mg/mL glucose and 5 mM taurine in the presence or absence of inhibitors. The reactions were triggered by adding the soluble stimulus Forbol Miristate Acetate PMA or zymosan and incubated by additional 30 minutes. We found that pure diapocynin was not better than apocynin regarding its scavenger and inhibitory properties. These results suggest that the formation of diapocynin is not essential for the action of apocynin as inhibitor of NADPH oxidase activation

Bidens pilosa L: efeitos protetores na inflamação intestinal

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeitos da dieta enriquecida com frutos das palmeiras Euterpe oleracea Mart. e Mauritia flexuosa L.f. na inflamação intestinal em ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Hypobromous acid, a powerful endogenous electrophile: Experimental and theoretical studies

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Bioactivity of pyridine-2-thiolato-1-oxide metal complexes: Bi(III), Fe(III) and Ga(III) complexes as potent anti-Mycobacterium tuberculosis prospective agents

In the search for new therapeutic tools against tuberculosis and to further address the therapeutic potential of pyridine-2-thiol 1-oxide (Hmpo) metal complexes, two new octahedral [M(III)(mpo)3] complexes, with M = Ga or Bi, were synthesized and characterized in the solid state and in solution. Attempts to crystallize [Ga(III)(mpo)3] in CH2Cl2 led to single crystals of the reaction product [GaCl(mpo)2], where the gallium(III) ion is in a square basis pyramidal environment, trans-coordinated at the basis to two pyridine-2-thiolato 1-oxide anions acting as bidentate ligands through their oxygen and sulfur atoms. The biological activity of the new [M(III)(mpo)3] complexes together with that of the previously reported Fe(III) analogous compound and the pyridine-2-thiol 1-oxide sodium salt (Na mpo) was evaluated on Mycobacterium tuberculosis. The compounds showed excellent activity, both in the standard strain H37Rv ATCC 27294 (pan-susceptible) and in five clinical isolates that are resistant to the standard first-line anti-tuberculosis drugs isoniazid and rifampicin. These pyridine-2-thiol 1-oxide derivatives are promising compounds for the treatment of resistant tuberculosis.

Experimental evidence of MAP kinase gene expression on the response of intestinal anti-inflammatory drugs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Experimental evidence of heparanase, Hsp70 and NF-κB gene expression on the response of anti-inflammatory drugs in TNBS-induced colonic inflammation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Desenvolvimento de nano e micropartículas de quitosana encapsulando 4-metilesculetina e avaliação no tratamento da doença inflamatória intestinal

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Role of transient receptor potential vanilloid 4 in rat joint inflammation

Objective To determine whether activation of transient receptor potential vanilloid 4 (TRPV-4) induces inflammation in the rat temporomandibular joint (TMJ), and to assess the effects of TRPV-4 agonists and proinflammatory mediators, such as a protease-activated receptor 2 (PAR-2) agonist, on TRPV-4 responses. Methods Four hours after intraarticular injection of carrageenan into the rat joints, expression of TRPV-4 and PAR-2 in trigeminal ganglion (TG) neurons and in the TMJs were evaluated by real-time reverse transcriptionpolymerase chain reaction and immunofluorescence, followed by confocal microscopy. The functionality of TRPV-4 and its sensitization by a PAR-2activating peptide (PAR-2AP) were analyzed by measuring the intracellular Ca2+ concentration in TMJ fibroblast-like synovial cells or TG neurons. Plasma extravasation, myeloperoxidase activity, and the head-withdrawal threshold (index of mechanical allodynia) were evaluated after intraarticular injection of selective TRPV-4 agonists, either injected alone or coinjected with PAR-2AP. Results In the rat TMJs, TRPV-4 and PAR-2 expression levels were up-regulated after the induction of inflammation. Two TRPV-4 agonists specifically activated calcium influx in TMJ fibroblast-like synovial cells or TG neurons. In vivo, the agonists triggered dose-dependent increases in plasma extravasation, myeloperoxidase activity, and mechanical allodynia. In synovial cells or TG neurons, pretreatment with PAR-2AP potentiated a TRPV-4 agonistinduced increase in [Ca2+]i. In addition, TRPV-4 agonistinduced inflammation was potentiated by PAR-2AP in vivo. Conclusion In this rat model, TRPV-4 is expressed and functional in TG neurons and synovial cells, and activation of TRPV-4 in vivo causes inflammation in the TMJ. Proinflammatory mediators, such as PAR-2 agonists, sensitize the activity of TRPV-4. These results identify TRPV-4 as an important signal of inflammation in the joint.