Study of LEP, MRAP2 and POMC genes as potential causes of severe obesity in Brazilian patients.

PURPOSE: Monogenic forms of obesity are caused by single-gene variants which affect the energy homeostasis by increasing food intake and decreasing energy expenditure. Most of these variants result from disruption of the leptin-melanocortin signaling, which can cause severe early-onset obesity and hyperphagia. These mutation have been identified in genes encoding essential proteins to this pathway, including leptin (LEP), melanocortin 2 receptor accessory proteins 2 (MRAP2) and proopiomelanocortin (POMC). We aimed to investigate the prevalence of LEP, MRAP2 and POMC rare variants in severely obese adults, who developed obesity during childhood. To the best of our knowledge, this is the first study screening rare variants of these genes in patients from Brazil. METHODS: A total of 122 Brazilian severely obese patients (BMI ≥ 35 kg/m2) were screened for the coding regions of LEP, MRAP2 and POMC by Sanger sequencing. All patients are candidates to the bariatric surgery. Clinical characteristics were described in patients with novel and/or potentially pathogenic variants. RESULTS: Sixteen different variants were identified in these genes, of which two were novel. Among them, one previous variant with potentially deleterious effect in MRAP2 (p.Arg125Cys) was found. In addition, two heterozygous mutations in POMC (p.Phe87Leu and p.Arg90Leu) were predicted to impair protein function. We also observed a POMC homozygous 9 bp insertion (p.Gly99_Ala100insSerSerGly) in three patients. No pathogenic variant was observed in LEP. CONCLUSION: Our study described for the first time the prevalence of rare potentially pathogenic MRAP2 and POMC variants in a cohort of Brazilian severely obese adults. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity.

BACKGROUND: The melanocortinergic pathway orchestrates the energy homeostasis and impairments in this system often lead to an increase in body weight. Rare variants in the melanocortin 4 receptor (MC4R) gene resulting in partial or complete loss of function have been described with autosomal co-dominant inheritance. These mutations are the most common cause of non-syndromic monogenic obesity. In this context, this study aimed to sequence the MC4R gene in a Brazilian cohort of adults with severe obesity. METHODS: This study included 163 unrelated probands with Body Mass Index (BMI) ≥ 35 kg/m2, stratified into three groups, according to the period of obesity onset. From the total sample, 25 patients were enrolled in the childhood-onset group (0-11 years), 19 patients in the adolescence/youth-onset group (12-21 years), and 119 patients in the adult-onset group (>21 years). Blood pressure, anthropometric and biochemical characteristics were obtained, and the MC4R coding region of each subject's DNA was assessed using automated Sanger sequencing. RESULTS: Significant anthropometric differences between the groups were observed. Higher body weight and BMI medians were found in patients with childhood-onset or adolescence/youth-onset when compared to the adulthood-onset obesity group. A total of five mutations were identified, including four missense variants: p.Ser36Thr, p.Val103Ile, p.Ala175Thr, and p.Ile251Leu. Additionally, we observed one synonymous variant (p.Ile198=). The p.Ala175Thr variant was identified in a female case with severe obesity and adulthood-onset. This variant was previously described as a partial loss-of-function mutation, in which the minor allele poses dominant-negative effect, probably resulting in reduced cAMP activity. CONCLUSION: This study showed a prevalence of common and rare variants in a cohort of Brazilian adults with severe obesity and candidates to bariatric surgery. We have identified a rare potentially pathogenic MC4R variant in a Brazilian patient with severe and adulthood-onset obesity.

Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis.

Sepsis is characterized by a life-threatening organ dysfunction caused by an unbalanced host response to microbe infection that can lead to death. Besides being currently the leading cause of death in intensive care units worldwide, sepsis can also induce long-term consequences among survivors, such as cognitive impairment. Statins (lipid-lowering drugs widely used to treat dyslipidemia) have been shown to possess pleiotropic anti-inflammatory and antimicrobial effects. These drugs act inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, an enzyme that catalyzes the conversion of HMG-CoA to mevalonate, the limiting step in cholesterol biosynthesis. In this work, we evaluated the therapeutic effects of simvastatin in an animal model of sepsis. In previous study from our group, statin pretreatment avoided cognitive damage and neuroinflammation in sepsis survivors. Herein, we focused on acute inflammation where sepsis was induced by cecal ligation and puncture (CLP), and the animals were treated with simvastatin (2 mg/kg) 6 h after surgery. We measured plasma biochemical markers of organ dysfunction, cell migration, cell activation, bacterial elimination, production of nitric oxide 24 h after CLP, survival rate for 7 days, and cognitive impairment 15 days after CLP. One single administration of simvastatin 6 h after CLP was able to prevent both liver and kidney dysfunction. In addition, this drug decreased cell accumulation in the peritoneum as well as the levels of TNF-α, MIF, IL-6, and IL-1ß. Simvastatin diminished the number of bacterial colony forming units (CFU) and increased the production of nitric oxide production in the peritoneum. Simvastatin treatment increased survival for the first 24 h, but it did not alter survival rate at the end of 7 days. Our results showed that posttreatment with simvastatin hampered organ dysfunction, increased local production of nitric oxide, improved bacterial clearance, and modulated inflammation in a relevant model of sepsis.

Adoptive Transfer of Bone Marrow-Derived Monocytes Ameliorates Schistosoma mansoni -Induced Liver Fibrosis in Mice.

Liver diseases are a major health problem worldwide leading to high mortality rates and causing a considerable economic burden in many countries. Cellular therapies as potential treatments for liver diseases have proven beneficial in most of the conditions. In recent years, studies involving therapy with bone marrow cells have been implemented to promote liver regeneration and to reduce hepatic fibrosis, however identifying the cell population present in the bone marrow that is responsible for hepatic improvement after therapy is still necessary. The aim of the present study was the evaluation of the therapeutic efficacy of monocytes obtained from bone marrow in fibrosis resulting from S. mansoni infection in C57BL/6 mice. Monocytes were isolated by immunomagnetic separation and administered to the infected animals. The effects of treatment were evaluated through morphometric, biochemical, immunological and molecular analyzes. Monocyte therapy promoted reduction of liver fibrosis induced by S. mansoni infection, associated with a decrease in production of inflammatory and pro-fibrogenic mediators. In addition, monocyte infusion caused downregulation of factors associated with the M1 activation profile, as well as upregulation of M2reg markers. The findings altogether reinforce the hypothesis that the predominance of M2reg macrophages, producers of immunosuppressive cytokines, may favor the improvement of hepatic fibrosis in a preclinical model, through fibrous tissue remodeling, modulation of the inflammatory response and fibrogenesis.

Omega-9 Oleic Acid, the Main Compound of Olive Oil, Mitigates Inflammation during Experimental Sepsis.

The Mediterranean diet, rich in olive oil, is beneficial, reducing the risk of cardiovascular diseases and cancer. Olive oil is mostly composed of the monounsaturated fatty acid omega-9. We showed omega-9 protects septic mice modulating lipid metabolism. Sepsis is initiated by the host response to infection with organ damage, increased plasma free fatty acids, high levels of cortisol, massive cytokine production, leukocyte activation, and endothelial dysfunction. We aimed to analyze the effect of omega-9 supplementation on corticosteroid unbalance, inflammation, bacterial elimination, and peroxisome proliferator-activated receptor (PPAR) gamma expression, an omega-9 receptor and inflammatory modulator. We treated mice for 14 days with omega-9 and induced sepsis by cecal ligation and puncture (CLP). We measured systemic corticosterone levels, cytokine production, leukocyte and bacterial counts in the peritoneum, and the expression of PPAR gamma in both liver and adipose tissues during experimental sepsis. We further studied omega-9 effects on leukocyte rolling in mouse cremaster muscle-inflamed postcapillary venules and in the cerebral microcirculation of septic mice. Here, we demonstrate that omega-9 treatment is associated with increased levels of the anti-inflammatory cytokine IL-10 and decreased levels of the proinflammatory cytokines TNF-α and IL-1ß in peritoneal lavage fluid of mice with sepsis. Omega-9 treatment also decreased systemic corticosterone levels. Neutrophil migration from circulation to the peritoneal cavity and leukocyte rolling on the endothelium were decreased by omega-9 treatment. Omega-9 also decreased bacterial load in the peritoneal lavage and restored liver and adipose tissue PPAR gamma expression in septic animals. Our data suggest a beneficial anti-inflammatory role of omega-9 in sepsis, mitigating leukocyte rolling and leukocyte influx, balancing cytokine production, and controlling bacterial growth possibly through a PPAR gamma expression-dependent mechanism. The significant reduction of inflammation detected after omega-9 enteral injection can further contribute to the already known beneficial properties facilitated by unsaturated fatty acid-enriched diets.

Leprosy and its reactional episodes: Serum levels and possible roles of omega-3 and omega-6-derived lipid mediators.

The disease leprosy is caused by Mycobacterium leprae. The disease displays a spectrum of clinical manifestations relating to the stage of the infection and the pathogen-specific immune response. The most frequent M. leprae-specific hypersensitivity reactions are erythema nodosum leprosum (ENL) and type-1 (reversal) reaction (T1R). Omega-3 and omega-6 fatty acid-derived lipid mediators are involved in the regulation of these M. leprae-specific inflammatory and immune responses. Studies on lipid mediators showed their presence during different manifestations of leprosy-before and after multidrug therapy (MDT) and during T1R. This review aims to compare the lipid mediators at different stages of the disease. This review also presents new data on the significance of lipid mediators (cysteinyl leukotrienes and leukotriene B4, prostaglandin E2 and D2, lipoxin A4 and resolvin D1) on ENL.

Leishmania infantum lipophosphoglycan induced-Prostaglandin E2 production in association with PPAR-γ expression via activation of Toll like receptors-1 and 2.

Lipophosphoglycan (LPG) is a key virulence factor expressed on the surfaces of Leishmania promastigotes. Although LPG is known to activate macrophages, the underlying mechanisms resulting in the production of prostaglandin E2 (PGE2) via signaling pathways remain unknown. Here, the inflammatory response arising from stimulation by Leishmania infantum LPG and/or its lipid and glycan motifs was evaluated with regard to PGE2 induction. Intact LPG, but not its glycan and lipid moieties, induced a range of proinflammatory responses, including PGE2 and nitric oxide (NO) release, increased lipid droplet formation, and iNOS and COX2 expression. LPG also induced ERK-1/2 and JNK phosphorylation in macrophages, in addition to the release of PGE2, MCP-1, IL-6, TNF-α and IL-12p70, but not IL-10. Pharmacological inhibition of ERK1/2 and PKC affected PGE2 and cytokine production. Moreover, treatment with rosiglitazone, an agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ), also modulated the release of PGE2 and other proinflammatory mediators. Finally, we determined that LPG-induced PPAR-γ signaling occurred via TLR1/2. Taken together, these results reinforce the role played by L. infantum-derived LPG in the proinflammatory response seen in Leishmania infection.

Hepatic myofibroblasts derived from Schistosoma mansoni-infected mice are a source of IL-5 and eotaxin: controls of eosinophil populations in vitro.

BACKGROUND: Hepatic myofibroblasts are relevant for pathogenesis of S. mansoni infection. In normal liver, these perisinusoidal cells are quiescent, express the lipocyte phenotype, and are located in the Disse's space, being the major site of vitamin A storage. When activated, they convert to myofibroblasts and contribute to granulomatous and diffuse liver fibrosis. In the present work, we observed that myofibroblasts obtained from granulomatous periovular inflammatory reactions in schistosome-infected mice (GR-MF) produce in vitro immunomodulatory cytokines for eosinophil activation: IL-5 and eotaxin. METHODS AND RESULTS: The secretory activity of GR-MF was detected after TGF-ß and IL-13 stimulation using 2D and 3D cell culture systems. In a mixed co-culture system using GR-MF with hematopoietic bone marrow cells from infected mice, we observed eosinophil survival that was dependent upon IL-5 and eotaxin, since antibodies against this cytokines decreased eosinophil population, as measured by eosinophil peroxidase activity. CONCLUSION: These results indicate that GR-MF may contribute to maintenance of local eosinophilia in schistosomal hepatic granulomas, and can function as immunoregulatory cells, besides their role in production of fibrosis.

Schistosome infection-derived Hepatic Stellate Cells are cellular source of prostaglandin D2: role in TGF-ß-stimulated VEGF production.

Hepatic Stellate Cells (HSCs) play a crucial role in pathogenesis of liver inflammation and fibrosis. During chronic liver injury, HSCs lose vitamin A and transform into myofibroblastic cells. In schistosomal granulomas, these activated HSCs are called GR-HSCs. Schistosomal-triggered hepatic fibrogenesis has TGF-ß as the most potent fibrogenic stimulus, that also controls gene expression of the angiogenic molecule VEGF in HSCs. COX-dependent production of prostaglandins (PGs) also play role in angiogenic processes. Besides angiogenic roles, prostanoids control immunomodulation of Schistosoma mansoni infection. Specifically, schistosoma-derived PGD2 has emerged as a key parasite regulator of immune defense evasion, while no role is still established to host PGD2. Therefore, the aim of this work is to investigate the ability of GR-HSCs to synthesize COX-derived PGD2 and a potential role of this prostanoid in VEGF production by GR-HSCs in vitro. Here, we confirmed that GR-HSCs express COX-2, which displayed perinuclear localization. While unstimulated GR-HSCs produce basal levels of PGD2, TGF-ß stimulation besides increasing COX2- mRNA levels, enhanced synthesis/secretion of PGD2 in GR-HSCs supernatant. Moreover, GR-HSCs-derived PGD2 mediate VEGF production by TGF-ß-stimulated GR-HSCs, since the pre-treatment with HQL-79, an inhibitor of hematopoietic PGD synthase inhibited both PGD2 synthesis and VEGF secretion by TGF-ß-stimulated GR-HSCs. All together, our findings show an autocrine/paracrine activity of GR-HSCs-derived PGD2 on TGF-ß-induced VEGF production by GR-HSCs, unveiling a role for PGD2 as important regulator of HSCs activation in hepatic granulomas from schistosome infected mice.

Time course of pulmonary burden in mice exposed to residual oil fly ash.

Residual oil fly ash (ROFA) is a common pollutant in areas where oil is burned. This particulate matter (PM) with a broad distribution of particle diameters can be inhaled by human beings and putatively damage their respiratory system. Although some studies deal with cultured cells, animals, and even epidemiological issues, so far a comprehensive analysis of respiratory outcomes as a function of the time elapsed after exposure to a low dose of ROFA is wanted. Thus, we aimed to investigate the time course of mechanical, histological, and inflammatory lung changes, as well as neutrophils in the blood, in mice exposed to ROFA until 5 days after exposure. BALB/c mice (25 ± 5 g) were randomly divided into 7 groups and intranasally instilled with either 10 µL of sterile saline solution (0.9% NaCl, CTRL) or ROFA (0.2 µg in 10 µL of saline solution). Pulmonary mechanics, histology (normal and collapsed alveoli, mononuclear and polymorphonuclear cells, and ultrastructure), neutrophils (in blood and bronchoalveolar lavage fluid) were determined at 6 h in CTRL and at 6, 24, 48, 72, 96, and 120 h after ROFA exposure. ROFA contained metal elements, especially iron, polycyclic aromatic hydrocarbons (PAHs), and organochlorines. Lung resistive pressure augmented early (6 h) in the course of lung injury and other mechanical, histological and inflammatory parameters increased at 24 h, returning to control values at 120 h. Blood neutrophilia was present only at 24 and 48 h after exposure. Swelling of endothelial cells with adherent neutrophils was detected after ROFA instillation. No neutrophils were present in the lavage fluid. In conclusion, the exposure to ROFA, even in low doses, induced early changes in pulmonary mechanics, lung histology and accumulation of neutrophils in blood of mice that lasted for 4 days and disappeared spontaneously.

Murine lung injury caused by Leptospira interrogans glycolipoprotein, a specific Na/K-ATPase inhibitor.

BACKGROUND: Leptospiral glycolipoprotein (GLP) is a potent and specific Na/K-ATPase inhibitor. Severe pulmonary form of leptospirosis is characterized by edema, inflammation and intra-alveolar hemorrhage having a dismal prognosis. Resolution of edema and inflammation determines the outcome of lung injury. Na/K-ATPase activity is responsible for edema clearance. This enzyme works as a cell receptor that triggers activation of mitogen-activated protein kinase (MAPK) intracellular signaling pathway. Therefore, injection of GLP into lungs induces injury by triggering inflammation. METHODS: We injected GLP and ouabain, into mice lungs and compared their effects. Bronchoalveolar lavage fluid (BALF) was collected for cell and lipid body counting and measurement of protein and lipid mediators (PGE2 and LTB4). The levels of the IL-6, TNFα, IL-1B and MIP-1α were also quantified. Lung images illustrate the injury and whole-body plethysmography was performed to assay lung function. We used Toll-like receptor 4 (TLR4) knockout mice to evaluate leptospiral GLP-induced lung injury. Na/K-ATPase activity was determined in lung cells by nonradioactive rubidium incorporation. We analyzed MAPK p38 activation in lung and in epithelial and endothelial cells. RESULTS: Leptospiral GLP and ouabain induced lung edema, cell migration and activation, production of lipid mediators and cytokines and hemorrhage. They induced lung function alterations and inhibited rubidium incorporation. Using TLR4 knockout mice, we showed that the GLP action was not dependent on TLR4 activation. GLP activated of p38 and enhanced cytokine production in cell cultures which was reversed by a selective p38 inhibitor. CONCLUSIONS: GLP and ouabain induced lung injury, as evidenced by increased lung inflammation and hemorrhage. To our knowledge, this is the first report showing GLP induces lung injury. GLP and ouabain are Na/K-ATPase targets, triggering intracellular signaling pathways. We showed p38 activation by GLP-induced lung injury, which was may be linked to Na/K-ATPase inhibition. Lung inflammation induced by GLP was not dependent on TLR4 activation.

Culture of mouse peritoneal macrophages with mouse serum induces lipid bodies that associate with the parasitophorous vacuole and decrease their microbicidal capacity against Toxoplasma gondii

Lipid bodies [lipid droplets (LBs)] are lipid-rich organelles involved in lipid metabolism, signalling and inflammation. Recent findings suggest a role for LBs in host response to infection; however, the potential functions of this organelle in Toxoplasma gondii infection and how it alters macrophage microbicidal capacity during infection are not well understood. Here, we investigated the role of host LBs in T. gondii infection in mouse peritoneal macrophages in vitro. Macrophages cultured with mouse serum (MS) had higher numbers of LBs than those cultured in foetal bovine serum and can function as a model to study the role of LBs during intracellular pathogen infection. LBs were found in association with the parasitophorous vacuole, suggesting that T. gondii may benefit from this lipid source. Moreover, increased numbers of macrophage LBs correlated with high prostaglandin E2 (PGE2) production and decreased nitric oxide (NO) synthesis. Accordingly, LB-enriched macrophages cultured with MS were less efficient at controlling T. gondii growth. Treatment of macrophages cultured with MS with indomethacin, an inhibitor of PGE2 production, increased the microbicidal capacity against T. gondii. Collectively, these results suggest that culture with MS caused a decrease in microbicidal activity of macrophages against T. gondii by increasing PGE2 while lowering NO production.

Lysophosphatidylcholine triggers TLR2- and TLR4-mediated signaling pathways but counteracts LPS-induced NO synthesis in peritoneal macrophages by inhibiting NF-κB translocation and MAPK/ERK phosphorylation.

BACKGROUND: Lysophosphatidylcholine (LPC) is the main phospholipid component of oxidized low-density lipoprotein (oxLDL) and is usually noted as a marker of several human diseases, such as atherosclerosis, cancer and diabetes. Some studies suggest that oxLDL modulates Toll-like receptor (TLR) signaling. However, effector molecules that are present in oxLDL particles and can trigger TLR signaling are not yet clear. LPC was previously described as an attenuator of sepsis and as an immune suppressor. In the present study, we have evaluated the role of LPC as a dual modulator of the TLR-mediated signaling pathway. METHODOLOGY/PRINCIPAL FINDINGS: HEK 293A cells were transfected with TLR expression constructs and stimulated with LPC molecules with different fatty acid chain lengths and saturation levels. All LPC molecules activated both TLR4 and TLR2-1 signaling, as evaluated by NF-қB activation and IL-8 production. These data were confirmed by Western blot analysis of NF-қB translocation in isolated nuclei of peritoneal murine macrophages. However, LPC counteracted the TLR4 signaling induced by LPS. In this case, NF-қB translocation, nitric oxide (NO) synthesis and the expression of inducible nitric oxide synthase (iNOS) were blocked. Moreover, LPC activated the MAP Kinases p38 and JNK, but not ERK, in murine macrophages. Interestingly, LPC blocked LPS-induced ERK activation in peritoneal macrophages but not in TLR-transfected cells. CONCLUSIONS/SIGNIFICANCE: The above results indicate that LPC is a dual-activity ligand molecule. It is able to trigger a classical proinflammatory phenotype by activating TLR4- and TLR2-1-mediated signaling. However, in the presence of classical TLR ligands, LPC counteracts some of the TLR-mediated intracellular responses, ultimately inducing an anti-inflammatory phenotype; LPC may thus play a role in the regulation of cell immune responses and disease progression.

Oleic acid induces lung injury in mice through activation of the ERK pathway.

Oleic acid (OA) can induce acute lung injury in experimental models. In the present work, we used intratracheal OA injection to show augmented oedema formation, cell migration and activation, lipid mediator, and cytokine productions in the bronchoalveolar fluids of Swiss Webster mice. We also demonstrated that OA-induced pulmonary injury is dependent on ERK1/2 activation, since U0126, an inhibitor of ERK1/2 phosphorylation, blocked neutrophil migration, oedema, and lipid body formation as well as IL-6, but not IL-1ß production. Using a mice strain carrying a null mutation for the TLR4 receptor, we proved that increased inflammatory parameters after OA challenges were not due to the activation of the TLR4 receptor. With OA being a Na/K-ATPase inhibitor, we suggest the possible involvement of this enzyme as an OA target triggering lung inflammation.

Histopathological analysis of initial cellular response in TLR-2 deficient mice experimentally infected by Leishmania (L.) amazonensis.

Tegumentary leishmaniasis is an important public health problem in several countries. The capacity of the Leishmania species, at the initial moments of the infection, to invade and survive inside the host cells involves the interaction of surface molecules that are crucial in determining the evolution of the disease. Using C57BL/6 wild-type and TLR-2(-/-) mice infected with L. (L.) amazonensis, we demonstrated that TLR-2(-/-) mice presented eosinophilic granuloma in the ear dermis, different from C57BL/6 wild-type mice that presented a cellular profile characterized mainly by mononuclear cell infiltrates, besides neutrophils and eosinophils, during the two first week of infection. When the parasite load was evaluated, we found that the absence of TLR-2 lead to a significant reduction of the infection in deficient mice, when compared with C57BL/6 mice which were more susceptible to the infection. Using TLR-2 deficient mice, it was possible to show that the absence of this receptor determined the reduction of the parasite load and the recruitment of inflammatory cells during the two first weeks after L. (L.) amazonensis infection.

Atividade anti-inflamatória do óleo-resina da Copaífera reticulata em modelo inflamatório de edema de pata / Anti-inflammatory activity of the oil-resin Copaífera reticulata of model inflamatory paw edema

Objetivo: avaliar a ação do óleo-resina de copaíba da espécie copaifera reticulata como anti-inflamatório em modelos experimentais de reação inflamatória aguda. Método: o estudo experimental foi realizado no Laboratório de Imunofarmacologia da Fundação Instituto Oswaldo Cruz ? FIOCRUZ/RJ, foram utilizados 30 (trinta) camundongos da linhagem Swiss Webster (SW). O óleo-resina de copaíba utilizada foi extraído de árvore da espécie Copaífera reticulata. O modelo de inflamação aguda induzida por carragenina foi utilizado para avaliar o efeito anti-inflamatório das concentrações, foi utilizado o teste estatístico de Kruskal-Wallis para comparar os valores medianos conforme os grupos com nível de significância alfa = 0,05. Resultados: no grupo C500 ocorreu significativa redução do volume no instante T3; somente os grupos Indo e C10 apresentaram significativa redução do volume em T6. Não houve diferença estatisticamente significante no Índice de Inibição do Edema nos grupos (Indo, C10, C100 e C500) nos intantes T1, T3 e T6. Conclusão: a atividade anti-inflamatória do óleo-resina foi confirmada pelo modelo do edema de pata induzido por carragenina através da redução do volume deslocado.

Objective: To evaluate the action of the oil-resin of Copaiba Copaifera reticulata as anti-inflammatory effect in experimental models of acute inflammatory reaction. Method: A total of 30 (thirty) mice of Swiss strain Webster (SW). The oil-resin of Copaiba used was extracted from tree species Copaifera reticulata. The model of acute inflammation induced by carrageenan was used to evaluate the anti-inflammatory effect of the extracts, we used the statistical test of Kruskal-Wallis test to compare the median values for the different groups with a significance level alpha = 0.05. Results: The group C500 was a significant reduction in the volume at time T3, only the Indus and C10 groups showed significant reduction in volume at T6. There was no statistically significant difference in the Index of Inhibition of edema in groups (Indo, C10, C100 and C500), in the instant, T1, T3 and T6. Conclusion: The anti-inflammatory activity of oil-resin was confirmed by the model of paw edema induced by carrageenan by reducing the volume displaced.