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

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

Oleic acid inhibits lung Na/K-ATPase in mice and induces injury with lipid body formation in leukocytes and eicosanoid production

Submitted by sandra infurna ([email protected]) on 2016-01-26T11:43:07Z No. of bitstreams: 1 cassiano_albuquerque_etal_IOC_2013.pdf: 2143360 bytes, checksum: 8f5e5674d7c469c0ea089e8c27de22ed (MD5)Approved for entry into archive by sandra infurna ([email protected]) on 2016-01-26T12:03:05Z (GMT) No. of bitstreams: 1 cassiano_albuquerque_etal_IOC_2013.pdf: 2143360 bytes, checksum: 8f5e5674d7c469c0ea089e8c27de22ed (MD5)Made available in DSpace on 2016-01-26T12:03:05Z (GMT). No. of bitstreams: 1 cassiano_albuquerque_etal_IOC_2013.pdf: 2143360 bytes, checksum: 8f5e5674d7c469c0ea089e8c27de22ed (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense.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.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 do Rio de Janeiro. Departamento de Química Analítica. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Departamento de Química Analítica. Rio de Janeiro, 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 Mèdicas. Departamento de Medicina Interna. Rio de Janeiro, RJ, Brasil.Background: Acute respiratory distress syndrome (ARDS) can emerge from certain pathologies, such as sepsis, fat embolism and leptospirosis, in which the levels of unesterified fatty acids are increased in the patient’s plasma. ARDS is characterized by edema formation, and edema resolution occurs mainly due to the pneumocyte Na/K-ATPase activity. As previously described, increased oleic acid (OA) plasma concentrations induce lung injury by interfering with sodium transport. The first aim of this study was to develop a radioactivity-free assay to detect Na,K-ATPase activity ex vivo using a model of OA-induced lung injury in mice. We also investigated the relationship between Na/K-ATPase inhibition and OA-induced lung injury using ouabain-induced lung injury as a comparison, because of the well-described effect of ouabain as a Na/K-ATPase inhibitor. Methods: We developed a Na/K-ATPase assay based on the capture of non-radioactive Rb+ ions by mice lung tissue in the absence or presence of ouabain, a specific Na/K-ATPase inhibitor. Rb+ incorporation into the lung was measured by inductively coupled plasma-optical emission spectrometry (ICP-OES) after lung tissue mineralization. Na/K-ATPase activity was considered as the difference between Rb+ incorporation in the absence and in the presence of ouabain. Bronchoalveolar lavage fluid was collected for lung injury assessment. For this assessment, cell counting, lipid body enumeration and lipid mediator concentrations were measured. Histological analyses were used to determinate lung pathology. Whole body plethysmographic analysis was performed to assay lung function. Results: The lung Na/K-ATPase activity of mice was completely inhibited by an OA dose of 10 μmol, an effect also obtained with 10-3 μmol of ouabain, as demonstrated by the decreased Rb+ incorporation in the lungs. The same OA dose induced lung edema and inflammation with cell influx, lipid body formation, and leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) production. Ouabain also induced lung inflammation, as detected by histological examinations. As far as we know, this is the first time that ouabain-induced lung injury was shown. Both OA and ouabain induced functional lung pathology in mice simultaneously with inhibition of the lung Na/K-ATPase activity. Conclusions: We developed a new non-radioactive assay to quantified Na/K-ATPase in vivo. OA and ouabain inhibited in vivo Na/K-ATPase activity in the lungs and induced lung injury. Our data reinforce the idea that Na/K-ATPase inhibitors may worsen lung injury in specific pathological conditions

The Na/K-ATPase role as a signal transducer in lung inflammation

Acute respiratory distress syndrome (ARDS) is marked by damage to the capillary endothelium and alveolar epithelium following edema formation and cell infiltration. Currently, there are no effective treatments for severe ARDS. Pathologies such as sepsis, pneumonia, fat embolism, and severe trauma may cause ARDS with respiratory failure. The primary mechanism of edema clearance is the epithelial cells’ Na/K-ATPase (NKA) activity. NKA is an enzyme that maintains the electrochemical gradient and cell homeostasis by transporting Na+ and K+ ions across the cell membrane. Direct injury on alveolar cells or changes in ion transport caused by infections decreases the NKA activity, loosening tight junctions in epithelial cells and causing edema formation. In addition, NKA acts as a receptor triggering signal transduction in response to the binding of cardiac glycosides. The ouabain (a cardiac glycoside) and oleic acid induce lung injury by targeting NKA. Besides enzymatic inhibition, the NKA triggers intracellular signal transduction, fostering proinflammatory cytokines production and contributing to lung injury. Herein, we reviewed and discussed the crucial role of NKA in edema clearance, lung injury, and intracellular signaling pathway activation leading to lung inflammation, thus putting the NKA as a protagonist in lung injury pathology

DEVELOPMENT OF AN INTERACTIVE SOFTWARE TO STUDY ENERGETIC METABOLISM

INTRODUCTION: Technology allows the creation of dynamic interfaces and graphics, which enables the construction of different scenarios that simulate biochemical events at cellular and molecular level. Furthermore, games have the ability to amuse and stimulate students and thus keeping them interested and receptive. Therefore, digital games must be explored as teaching aids once they have features that enhance the teaching process. OBJECTIVES: This project aimed to develop an educational software that contributes to the understanding of various events taking place in energetic metabolism. MATERIALS AND METHODS: We developed a downloadable educational game in Java, divided into two levels, each of which tackle issues about the Krebs cycle, the respiratory chain and oxidative phosphorylation. Initially, the names of the components of the metabolic process appear randomly on computer screen and the user must follow clues to place them in the right sequence, until all the biochemical reactions are complete. In next phase, there is a quiz about details and clinical correlates related to the theme of the game. Finally, students have to answer a form in order to verify acceptance and relevance of the game. DISCUSSION AND RESULTS: The game was applied to 40 medical students from UFF. The game’s subject matter and its difficulty were analyzed and more than 40% of students classified both respiratory chain and Krebs cycle as difficult. These findings highlight the need to establish new methods to enhance the teaching and learning processes and decrease the students’ difficulties, which is the game’s purpose. The game was very highly rated by students once they evaluated the game as an excellent educational aid and 92% of students agreed that it complements the content discussed in classroom. Finally, 97,5% of students said they would play again. CONCLUSION: Therefore, educational games could be an excellent tool to optimize learning

Acute Respiratory Distress Syndrome: Role of Oleic Acid-Triggered Lung Injury and Inflammation

Submitted by sandra infurna ([email protected]) on 2016-02-22T15:05:28Z No. of bitstreams: 1 cassiano_albuquerque_etal_IOC_2015.pdf: 2378904 bytes, checksum: 36787e7d0e6457e85ecc64b7b9ff7a1c (MD5)Approved for entry into archive by sandra infurna ([email protected]) on 2016-02-22T15:15:50Z (GMT) No. of bitstreams: 1 cassiano_albuquerque_etal_IOC_2015.pdf: 2378904 bytes, checksum: 36787e7d0e6457e85ecc64b7b9ff7a1c (MD5)Made available in DSpace on 2016-02-22T15:15:50Z (GMT). No. of bitstreams: 1 cassiano_albuquerque_etal_IOC_2015.pdf: 2378904 bytes, checksum: 36787e7d0e6457e85ecc64b7b9ff7a1c (MD5) Previous issue date: 2015Fundação 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. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Niterói, 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.Lung injury especially acute respiratory distress syndrome (ARDS) can be triggered by diverse stimuli, including fatty acids and microbes. ARDS affects thousands of people worldwide each year, presenting high mortality rate and having an economic impact. One of the hallmarks of lung injury is edema formation with alveoli flooding. Animal models are used to study lung injury. Oleic acid-induced lung injury is a widely used model resembling the human disease. The oleic acid has been linked to metabolic and inflammatory diseases; here we focus on lung injury. Firstly, we briefly discuss ARDS and secondly we address the mechanisms by which oleic acid triggers lung injury and inflammation

Na/K Pump and Beyond: Na/K-ATPase as a Modulator of Apoptosis and Autophagy

Submitted by Sandra Infurna ([email protected]) on 2017-11-21T16:24:49Z No. of bitstreams: 1 cassiano_albuquerque_etal_IOC_2017.pdf: 1297250 bytes, checksum: 52adfdd10a39f6337dba261eb5a5d466 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-11-21T16:36:33Z (GMT) No. of bitstreams: 1 cassiano_albuquerque_etal_IOC_2017.pdf: 1297250 bytes, checksum: 52adfdd10a39f6337dba261eb5a5d466 (MD5)Made available in DSpace on 2017-11-21T16:36:33Z (GMT). No. of bitstreams: 1 cassiano_albuquerque_etal_IOC_2017.pdf: 1297250 bytes, checksum: 52adfdd10a39f6337dba261eb5a5d466 (MD5) Previous issue date: 2017Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil / Universidade Federal do Estado do Rio de Janeiro. Departamento de Bioquímica. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Laboratório de Enzimologia e Sinalização Celular. Niterói, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Laboratório de Enzimologia e Sinalização Celular. Niterói, RJ, Brasil.Lung cancer is a leading cause of global cancer deaths. Na/K-ATPase has been studied as a target for cancer treatment. Cardiotonic steroids (CS) trigger intracellular signalling upon binding to Na/K-ATPase. Normal lung and tumour cells frequently express different pump isoforms. Thus, Na/K-ATPase is a powerful target for lung cancer treatment. Drugs targeting Na/K-ATPase may induce apoptosis and autophagy in transformed cells. We argue that Na/K-ATPase has a role as a potential target in chemotherapy in lung cancer treatment. We discuss the effects of Na/K-ATPase ligands and molecular pathways inducing deleterious effects on lung cancer cells, especially those leading to apoptosis and autophagy