Reduced Plasma Nonesterified Fatty Acid Levels and the Advent of an Acute Lung Injury in Mice after Intravenous or Enteral Oleic Acid Administration

Although exerting valuable functions in living organisms, nonesterified fatty acids (NEFAs) can be toxic to cells. Increased blood concentration of oleic acid (OLA) and other fatty acids is detected in many pathological conditions. In sepsis and leptospirosis, high plasma levels of NEFA and low albumin concentrations are correlated to the disease severity. Surprisingly, 24 h after intravenous or intragastric administration of OLA, main NEFA levels (OLA inclusive) were dose dependently decreased. However, lung injury was detected in intravenously treated mice, and highest dose killed all mice. When administered by the enteral route, OLA was not toxic in any tested conditions. Results indicate that OLA has important regulatory properties on fatty acid metabolism, possibly lowering circulating fatty acid through activation of peroxisome proliferator-activated receptors. The significant reduction in blood NEFA levels detected after OLA enteral administration can contribute to the already known health benefits brought about by unsaturated-fatty-acid-enriched diets

Toxoplasma gondii-skeletal muscle cells interaction increases lipid droplet biogenesis and positively modulates the production of IL-12, IFN-g and PGE2

Background: The interest in the mechanisms involved in Toxoplasma gondii lipid acquisition has steadily increased during the past few decades, but it remains not completely understood. Here, we investigated the biogenesis and the fate of lipid droplets (LD) of skeletal muscle cells (SkMC) during their interaction with T. gondii by confocal and electron microscopy. We also evaluated whether infected SkMC modulates the production of prostaglandin E2 (PGE2), cytokines interleukin-12 (IL-12) and interferon-gamma (INF-g), and also the cyclooxygenase-2 (COX-2) gene induction. Methods: Primary culture of skeletal muscle cells were infected with tachyzoites of T. gondii and analysed by confocal microscopy for observation of LD. Ultrastructural cytochemistry was also used for lipid and sarcoplasmatic reticulum (SR) detection. Dosage of cytokines (IL-12 and INF-g) by ELISA technique and enzyme-linked immunoassay (EIA) for PGE2 measurement were employed. The COX-2 gene expression analysis was performed by real time reverse transcriptase polymerase chain reaction (qRT-PCR). Results: We demonstrated that T. gondii infection of SkMC leads to increase in LD number and area in a time course dependent manner. Moreover, the ultrastructural analysis demonstrated that SR and LD are in direct contact with parasitophorous vacuole membrane (PVM), within the vacuolar matrix, around it and interacting directly with the membrane of parasite, indicating that LD are recruited and deliver their content inside the parasitophorous vacuole (PV) in T. gondii-infected SkMC. We also observed a positive modulation of the production of IL-12 and IFN-g, increase of COX-2 mRNA levels in the first hour of T. gondii-SkMC interaction and an increase of prostaglandin E2 (PGE2) synthesis from 6 h up to 48 h of infection. Conclusions: Taken together, the close association between SR and LD with PV could represent a source of lipids as well as other nutrients for the parasite survival, and together with the increased levels of IL-12, INF-g and inflammatory indicators PGE2 and COX-2 might contribute to the establishment and maintenance of chronic phase of the T. gondii infection in muscle cell

Reduced Plasma Nonesterified Fatty Acid Levels and the Advent of an Acute Lung Injury in Mice after Intravenous or Enteral Oleic Acid Administration

Although exerting valuable functions in living organisms, nonesterified fatty acids (NEFAs) can be toxic to cells. Increased blood concentration of oleic acid (OLA) and other fatty acids is detected in many pathological conditions. In sepsis and leptospirosis, high plasma levels of NEFA and low albumin concentrations are correlated to the disease severity. Surprisingly, 24 h after intravenous or intragastric administration of OLA, main NEFA levels (OLA inclusive) were dose dependently decreased. However, lung injury was detected in intravenously treated mice, and highest dose killed all mice. When administered by the enteral route, OLA was not toxic in any tested conditions. Results indicate that OLA has important regulatory properties on fatty acid metabolism, possibly lowering circulating fatty acid through activation of peroxisome proliferator-activated receptors. The significant reduction in blood NEFA levels detected after OLA enteral administration can contribute to the already known health benefits brought about by unsaturatedfatty-acid-enriched diets

Calcitonin gene-related peptide inhibits local acute inflammation and protects mice against lethal endotoxemia

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-04-14T12:53:24Z No. of bitstreams: 1 Gomes R N Calcitonin Gene-Related....pdf: 246981 bytes, checksum: 150c21fecaa94f3881dfbc333972094d (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-04-14T13:19:24Z (GMT) No. of bitstreams: 1 Gomes R N Calcitonin Gene-Related....pdf: 246981 bytes, checksum: 150c21fecaa94f3881dfbc333972094d (MD5)Made available in DSpace on 2015-04-14T13:19:24Z (GMT). No. of bitstreams: 1 Gomes R N Calcitonin Gene-Related....pdf: 246981 bytes, checksum: 150c21fecaa94f3881dfbc333972094d (MD5) Previous issue date: 2005Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Departamento de Fisiologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Departamento de Fisiologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Departamento de Fisiologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.University School of Veterinary Medicine. Division of Infectious Diseases. Department of Biomedical Sciences. North Grafton, Massachusettes, USA.Harvard School of Public Health. Department of Tropical Public Health. Boston, Massachusettes, USA.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Laboratório de Inflamação e Imunidade. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.ABSTRACT: Calcitonin gene-related peptide (CGRP), a potent vasodilatory peptide present in central and peripheral neurons, is released at inflammatory sites and inhibits several macrophage, dendritic cell, and lymphocyte functions. In the present study, we investigated the role of CGRP in models of local and systemic acute inflammation and on macrophage activation induced by lipopolysaccharide (LPS). Intraperitoneal pretreatment with synthetic CGRP reduces in approximately 50% the number of neutrophils in the blood and into the peritoneal cavity 4 h after LPS injection. CGRP failed to inhibit neutrophil recruitment induced by the direct chemoattractant platelet-activating factor, whereas it significantly inhibited LPSinduced KC generation, suggesting that the effect of CGRP on neutrophil recruitment is indirect, acting on chemokine production by resident cells. Pretreatment of mice with 1 mg of CGRP protects against a lethal dose of LPS. The CGRPinduced protection is receptor mediated because it is completely reverted by the CGRP receptor antagonist, CGRP 8-37. The protective effect of CGRP correlates with an inhibition of TNF-a and an induction of IL-6 and IL-10 in mice sera 90 min after LPS challenge. Finally, CGRP significantly inhibits LPS-induced TNF-a released from mouse peritoneal macrophages. These results suggest that activation of the CGRP receptor on macrophages during acute inflammation could be part of the negative feedback mechanism controlling the extension of acute inflammatory responses

Omega-9 Oleic Acid Induces Fatty Acid Oxidation and Decreases Organ Dysfunction and Mortality in Experimental Sepsis

Submitted by sandra infurna ([email protected]) on 2016-06-19T21:56:40Z No. of bitstreams: 1 flora_oliveira_etal_IOC_2016.PDF: 1127513 bytes, checksum: 2b33c8a8ebdd6279e2e149aaedca5a3a (MD5)Approved for entry into archive by sandra infurna ([email protected]) on 2016-06-19T22:20:25Z (GMT) No. of bitstreams: 1 flora_oliveira_etal_IOC_2016.PDF: 1127513 bytes, checksum: 2b33c8a8ebdd6279e2e149aaedca5a3a (MD5)Made available in DSpace on 2016-06-19T22:20:25Z (GMT). No. of bitstreams: 1 flora_oliveira_etal_IOC_2016.PDF: 1127513 bytes, checksum: 2b33c8a8ebdd6279e2e149aaedca5a3a (MD5) Previous issue date: 2016Made available in DSpace on 2016-07-08T12:22:05Z (GMT). No. of bitstreams: 3 flora_oliveira_etal_IOC_2016.PDF.txt: 55221 bytes, checksum: 6263327453588b424db910e20fddf55b (MD5) flora_oliveira_etal_IOC_2016.PDF: 1127513 bytes, checksum: 2b33c8a8ebdd6279e2e149aaedca5a3a (MD5) license.txt: 2991 bytes, checksum: 5a560609d32a3863062d77ff32785d58 (MD5) Previous issue date: 2016Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Faculdade de Ciências Médicas. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Niterói, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Médicas. Departamento de Medicina Interna. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade Estácio de Sá. Programa de Produtividade Científica. Rio de Janeiro, RJ, Brasil .Sepsis is characterized by inflammatory and metabolic alterations, which lead to massive cytokine production, oxidative stress and organ dysfunction. In severe systemic inflammatory response syndrome, plasma non-esterified fatty acids (NEFA) are increased. Several NEFA are deleterious to cells, activate Toll-like receptors and inhibit Na+/K+-ATPase, causing lung injury. A Mediterranean diet rich in olive oil is beneficial. Themain component of olive oil is omega-9 oleic acid (OA), a monounsaturated fatty acid (MUFA).We analyzed the effect of OA supplementation on sepsis. OA ameliorated clinical symptoms, increased the survival rate, prevented liver and kidney injury and decreased NEFA plasma levels inmice subjected to cecal ligation and puncture (CLP). OA did not alter food intake and weight gain but diminished reactive oxygen species (ROS) production and NEFA plasma levels. Carnitine palmitoyltransferase IA (CPT1A) mRNA levels were increased, while uncoupling protein 2 (UCP2) liver expression was enhanced in mice treated with OA. OA also inhibited the decrease in 5' AMPactivated protein kinase (AMPK) expression and increased the enzyme expression in the liver of OA-treated mice compared to septic animals.We showed that OA pretreatment decreased NEFA concentration and increased CPT1A and UCP2 and AMPK levels, decreasing ROS production.We suggest that OA has a beneficial role in sepsis by decreasing metabolic dysfunction, supporting the benefits of diets high inmonounsaturated fatty acids (MUFA)