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-alpha and IL-1 beta 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

Impacto da pneumonia grave no sistema nervoso centralefeitos de curto e longo prazo

Submitted by Gilvan Almeida ([email protected]) on 2017-04-10T17:39:16Z No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 72660.pdf: 4685946 bytes, checksum: fbe6ee3bb9fe4145ea8d4c6fd4f73de5 (MD5)Approved for entry into archive by Anderson Silva ([email protected]) on 2017-06-07T13:46:24Z (GMT) No. of bitstreams: 2 72660.pdf: 4685946 bytes, checksum: fbe6ee3bb9fe4145ea8d4c6fd4f73de5 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Made available in DSpace on 2017-06-07T13:46:24Z (GMT). No. of bitstreams: 2 72660.pdf: 4685946 bytes, checksum: fbe6ee3bb9fe4145ea8d4c6fd4f73de5 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2016Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, BrasilA pneumonia é definida como uma inflamação aguda do trato respiratório inferior, e atinge cerca de 450 milhões de pessoas em todo o mundo. A pneumonia pode resultar da infecção por bactéria, vírus e fungos e são classificadas em pneumonias adquiridas na comunidade e pneumonias nosocomiais. Essa doença também pode causar uma complicação pulmonar, chamada de síndrome do desconforto respiratório agudo (SDRA), que se caracteriza por dano endotelial com aumento da permeabilidade capilar, extravasamento de fluido protéico no espaço alveolar e edema pulmonar. Essa forma grave pode levar a uma inflamação sistêmica com consequente falência de múltiplos órgãos e sepse. Doenças infeciosas graves, como a pneumonia, podem acarretar alteração de longo prazo, como o comprometimento do sistema nervoso central (SNC). O conhecimento da fisiopatologia da encefalopatia associada à inflamação sistêmica ainda é bastante limitado e o desenvolvimento de novos modelos experimentais que sejam clinicamente relevantes pode ajudar no esclarecimento dos mecanismos envolvidos na encefalopatia, bem como atuar como ferramenta para o estudo de estratégias terapêuticas capazes de conter ou reverter a possível formação de sequelas neurocognitivas. Neste estudo tivemos como principal objetivo investigar os mecanismos neuroinflamatórios associados ao declínio cognitivo em um modelo experimental de pneumonia grave. Primeiramente foi necessária a validação de um modelo de pneumonia grave capaz de mimetizar a forma clínica da doença. Camundongos C57BL/6 foram divididos em grupo controle e grupo pneumonia (PA103). Os grupos controle receberam 50 µL de solução salina por instilação intratraqueal e o grupo pneumonia recebeu, pela mesma via e mesmo volume, solução contendo 105 CFU da bactéria Pseudomonas aeruginosa 103 Os processos inflamatórios locais e sistêmicos e histopatológicos no pulmão dos animais submetidos ao modelo de pneumonia bacteriana foram analisados. O modelo utilizado levou a uma diminuição da sobrevida dos animais e aumento do escore clínico dos mesmos. Observamos também que a instilação intratraqueal de PA103 provocou uma intensa migração celular para o parênquima pulmonar, acompanhado de formação de edema pulmonar e aumento de citocinas locais e sistêmicas, bem como uma diminuição da função pulmonar. Além disso, o modelo de pneumonia grave estabelecido no presente trabalho foi capaz de promover alterações importantes no SNC. As alterações agudas compreenderam a ativação de micróglia, aumento de mediadores inflamatórios, presença de estresse oxidativo e redução de proteínas sinápticas. As alterações a longo prazo compreenderam uma disfunção cognitiva 13 dias após o insulto pulmonar, tanto no modelo de pneumonia quanto no modelo de ligadura e punção cecal (CLP). No CLP observamos uma recuperação do dano cognitivo, ao contrário do modelo de pneumonia, onde essa alteração se manteve por 30 a 50 dias após o estímulo. Nossas análises também demonstraram persistência da diminuição de proteínas sinápticas observada agudamente. Nosso estudo, portanto, apresenta um modelo de pneumonia grave possivelmente capaz de promover um comprometimento cognitivo permanente. Adicionalmente, as evidências de alterações no SNC no modelo abordado proporciona mais uma ferramenta, clinicamente relevante, para o estudo do comprometimento cerebral observado em neuropatologias, em especial as que envolvem a interação entre resposta inflamatória periférica e SNCPneumonia is defined as an acute inflammation of the lower respiratory tract and affects about 450 million people worldwide. Pneumonia can result from infection by bacteria, viruses and fungi and are classified as community-acquired pneumonia and nosocomial pneumonia. This disease can also cause a pulmonary complication, known as acute respiratory distress syndrome (ARDS), characterized by endothelial damage with increased capillary permeability, fluid protein extravasation in the alveolar space and pulmonary edema. This most severe form can that lead to systemic inflammation with subsequent multiple organ failure and sepsis. Severe infectious diseases such as pneumonia, can cause long-term changes, such as CNS (central nervous system) involvement. The pathophysiology of encephalopathy associated with systemic inflammation is still limited and the development of new experimental models that are clinically relevant can help to clarify the mechanisms involved in encephalopathy, and act as a tool for the study of therapeutic strategies to contain or reverse the possible formation of neurocognitive sequelae. The main objective of this study was to investigate the neuroinflammatory mechanisms associated with the cognitive decline in an experimental model of severe pneumonia. First, we validated a severe pneumonia model able to mimic the clinical manifestations of the disease. C57BL/6 mice were divided into control group and pneumonia group (PA103). The control group received 50 µL of saline solution by intratracheal instillation and the pneumonia group received 50 µL of a solution containing 104 or 105 CFU of the bacteria Pseudomonas aeruginosa 103, also by intratracheal instillation The local and systemic inflammatory processes and histopathology in the lungs of the animals submitted to bacterial pneumonia model were analyzed. The model led to a decrease in the survival of animals and increased their clinical score. We also observed that intratracheal instillation of PA103 resulted in an intense cell migration into the lung parenchyma, accompanied by pulmonary edema formation and increased local and systemic cytokines, as well as a decline in lung function. In addition, the severe pneumonia model stablished in this study was able to induce significant changes in the CNS. The acute changes included microglial activation, increase in inflammatory mediators, the presence of oxidative stress and reduction in synaptic proteins. The long-term changes included cognitive dysfunction 13 days after lung insult, which unlike polymicrobial sepsis model, remained for 30 and 50 days after challenge. Our analysis also showed persistent decrease in synaptic proteins observed in the early time-point. Our study, therefore, presents an experimental pneumonia model possibly capable to induce a permanent cognitive impairment. Moreover, evidence of cognitive decline and long-term synaptic dysfunction presented in the addressed model provides another clinically relevant tool for the study of cerebral impairment seen in neuropathologies, specially those involving the interaction between peripheral inflammatory response and CN

Efeito da sinvastatina em um modelo experimental de sepse

Made available in DSpace on 2014-07-22T16:57:39Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 66980.pdf: 1324531 bytes, checksum: 1e497344aa46c88cdf2881941ee38024 (MD5) Previous issue date: 2014-06-03Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de janeiro, RJ, BrasilA sepse é uma condição médica severa, caracterizada por uma resposta inflamatória sistêmica (designada por Síndrome da Resposta Inflamatória Sistêmica), que ocorre em vigência de um quadro infeccioso, podendo evoluir para disfunção múltipla dos órgãos e morte. Atualmente é a principal causa de morte nas Unidades de Terapia Intensiva em todo o mundo. Nos últimos anos, diversos medicamentos foram testados na prevenção e tratamento da sepse, com resultados pouco animadores. Estudos recentes mostraram que as estatinas (drogas hipolipemiantes amplamente utilizadas no tratamento de dislipidemias) foram capazes de reduzir a mortalidade em pacientes sépticos, bem como o risco do desenvolvimento de sepse severa. As estatinas atuam inibindo a 3-hidroxi-3-metilglutaril-coenzima A (HMG-CoA) redutase, enzima que catalisa a conversão da HMG-CoA em mevalonato, etapa limitante na biosíntese do colesterol. Além de agirem na diminuição do colesterol sérico, as estatinas estão emergindo como potentes inibidores de processos inflamatórios, ações conhecidas como efeitos pleiotrópicos. Neste estudo tivemos como principal objetivo a avaliação dos efeitos da sinvastatina em um modelo de ligadura e punção cecal (CLP), especificamente sobre a taxa de sobrevida e parâmetros inflamatórios, como migração celular, ativação celular, eliminação bacteriana e produção de óxido nítrico Observamos que a sinvastatina foi capaz de causar uma tendência de melhora nas funções renais e hepáticas de animais submetidos ao CLP. Observamos também que 24 horas após a cirurgia houve aumento da migração celular para o peritôneo, ocorrendo uma tendência de reversão deste efeito após o tratamento com sinvastatina (2 mg/kg). Nossos resultados também mostraram que a sinvastatina foi capaz de reduzir os níveis de TNF-\F061, MIF, IL-6 e IL1\F062. Nossos resultados mostraram um aumento significativo na produção de óxido nítrico no peritôneo de animais que receberam o tratamento com sinvastatina, o que pode estar relacionado com o resultado obtido na contagem de Unidades Formadoras de Colônias, da qual houve uma tendência de diminuição. O tratamento com sinvastatina ainda mostrou poder ser capaz de diminuir a produção de óxido nítrico na corrente sanguínea. Observamos, também, alteração na formação de corpúsculos lipídicos de células provenientes do lavado peritoneal de camundongos tratados com a droga, sendo este número menor nesses animais. E ainda, foi observado um efeito in vitro da droga sobre macrófagos peritoneais, havendo diminuição do CFU em todas as concentrações utilizadas. Nossos estudos, portanto, indicam que os efeitos da sinvastatina estão relacionados a determinantes da fisiopatologia da sepse, o que torna de grande importância a contínua avaliação de seus mecanismos de ação, para que possivelmente esta droga seja implementada como terapia adjuvante no tratamento da sepseSepsis is a severe medical condition characterized by a systemic inflammatory response (called systemic inflammatory response syndrome), which occurs in the presence of an infection, may progress to multiple organ dysfunction and death. It is currently the leading cause of death in intensive care units worldwide. In recent years, several drugs were tested in the prevention and treatment of sepsis, without good results. Recent studies have shown that statins (lipid-lowering drugs widely used to treat dyslipidemia) were able to reduce mortality in septic patients, as well as the risk of developing severe sepsis. Statins act by 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 addition to acting in the reduction of serum cholesterol, statins are emerging as potent inhibitors of inflammatory processes, actions known as pleiotropic effects. This study had as main objective the evaluation of the effects of simvastatin in a model of cecal ligation and puncture (CLP), specifically on the rate of survival and inflammatory parameters, such as cell migration, cell activation, bacterial elimination and production of nitric oxide. We found that simvastatin was able to cause a trend toward improvement in kidney function and liver of animals subjected to CLP. We also note that 24 hours after surgery there was an increase of cell migration to the peritoneum, causing a trend reversal of this effect after treatment with simvastatin (2mg/kg). And also our results showed that simvastatin was able to reduce the levels of TNF-, MIF, IL-6 and IL1. Our results showed a significant increase in the production of nitric oxide in the peritoneum of animals that received treatment with simvastatin, which may be related to the result obtained in the counting of colony forming units, of which was diminished. Treatment with simvastatin also showed to be able to decrease the production of nitric oxide in the bloodstream. We also observe changes in the formation of lipid bodies from the peritoneal cavity of mice treated with the drug, this number is lower in these animals. And yet, there was a drug effect in vitro on peritoneal macrophages, with the CFU decrease at all concentrations used. Our studies thus indicate that the effects of simvastatin are related to determinants of the pathophysiology of sepsis, which makes it of great importance to continuing evaluation of its mechanisms of action, possibly to be implemented as adjunctive therapy in the treatment of sepsis

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)

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-1β. 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

Na/K-ATPase assay in the intact mice lung subjected to perfusion

Made available in DSpace on 2015-05-27T13:39:50Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) adriana_silvaetal_IOC_2014.pdf: 350633 bytes, checksum: 5135d467f38c8b0fb3cbe9daca32f22b (MD5) Previous issue date: 2014Fundação 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.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Bio-Manguinhos. Departamento de Reativos para Diagnóstico. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Bio-Manguinhos. Departamento de Reativos para Diagnóstico. 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 Federal do Rio de Janeiro. Departamento de Química Analítica. Rio de Janeiro, RJ, Brasil.Among the characteristics of acute respiratory distress syndrome (ARDS) is edema formation and its resolution depends on pneumocyte Na/K-ATPase activity. Increased concentration of oleic acid (OA) in plasma induces lung injury by targeting Na/K-ATPase and, thus, interfering in sodium transport. FINDINGS: Presently, we adapted a radioactivity-free assay to detect Na/K-ATPase activity in perfused lung mice, comparing the inhibitory effect of ouabain and OA. We managed to perfuse only the lung, avoiding the systemic loss of rubidium. Rb+ incorporation into lung was measured by inductively coupled plasma optical emission spectrometry (ICP OES) technique, after lung tissue digestion. Na/K-ATPase activity was the difference between Rb+ incorporation with or without ouabain. Lung Na/K-ATPase was completely inhibited by perfusion with ouabain. However, OA caused a partial inhibition. CONCLUSIONS: In the present work the amount of incorporated Rb+ was greater than seen in our previous report, showing that the present technique is trustworthy. This new proposed assay may allow researchers to study the importance of Na/K-ATPase activity in lung pathophysiology

Oleic acid increases the transcription of the CPT1A gene in septic mice.

<p>Swiss mice were treated for 14 days with oleic acid. On the 15^th day, mice were subjected to CLP. The liver was removed 24 hours after CLP. CPT1A mRNA was detected by RT-PCR. A representative gel of (A) CPT1A and of the (B) control GAPDH gene transcription. The loading control was GAPDH. (C)The bands were analyzed by densitometry and are represented as the CPT1A/GAPDH ratio. Values represent mean and SEM from 5–6 animals per group.</p

Oleic acid administration improves survival and ameliorates clinical score in septic mice.

<p>Animals were treated with oleic acid for 14 days. On the 15^th day, mice were subjected to CLP, and (A) 6 and (B) 24 hours after surgery, the clinical score was evaluated as described in the Materials and Methods. (C) The survival rate was assessed for 7 days after CLP. Control groups received saline. Each group consisted of 15 to 23 animals (clinical score at 6 hours: sham = 15 animals, sham + OA = 18 animals and CLP and CLP + OA = 23 animal; at 24 hours: sham and sham + OA = 18 animals, CLP = 18 animals, CLP + OA = 22 animals) in 3 independent experiments. For survival rates, 10 animals from each group were analyzed. This is a representative curve from 3 independent experiments. p < 0.05 * CLP vs sham, # CLP vs CLP plus oleic acid; log-rank test for mortality and one-way ANOVA followed by Newman-Keuls test for the clinical score.</p

OA alters fatty acid metabolism and organ dysfunction and improves sepsis outcome.

<p>CPT1A –carnitine palmitoyltransferase 1A; PPAR–peroxisome proliferator-activated receptor, UCP2 –uncoupling protein 2; AMPK—5' AMP-activated protein kinase. OA activates AMPK, increases CPT1A and UCP2 and decreases fatty acid synthesis, resulting in an increase in oxidative processes. PPAR activation leads to an increase in the expression of CPT1A and UCP2; consequently, the fatty acid oxidation will be enhanced. Augmented fatty acid oxidation leads to a decrease in the NEFA plasma levels. Decreased NEFA and ROS levels would improve organ dysfunction and increase survival rate.</p

Oleic acid treatment decreases MDA formation, and induces UCP2 and AMPK in septic mice.

<p>Mice were treated for 14 days with oleic acid, and on the 15^th day, CLP was performed. The liver was removed 24 hours after CLP for analysis of (A) MDA and (B) UCP2 by western blotting. The graph shows the densitometric analysis of the UCP2, AMPK and β-actin bands, as described in the methods. The results are expressed as the mean <i>±</i> SEM of 5–6 animals. (* and +) p < 0.05 compared to sham and sham + OA (respectively) and (#) compared to CLP.</p