Oxidative Damage, Inflammation, and Toll-Like Receptor 4 Pathway Are Increased in Preeclamptic Patients: A Case-Control Study

Problem. There was no direct correlation between plasma and placental oxidative damage parameters and inflammation and evidence of TLR4 pathway activation in the placenta in preeclamptic (PE) patients. Method of Study. 33 PE patients and 33 normotensive pregnant women were included. The maternal section of the placenta and blood were collected to the determination of oxidative damage markers (thiobarbituric acid reactive species and protein carbonyls), inflammatory response (interleukin-6 and myeloperoxidase activity), and activation of the TLR-4-NF-kB pathway. Results. An increase of IL-6 levels in both plasma and placenta was observed, but myeloperoxidase activity was not significantly different comparing the groups. Oxidative damage parameters were increased in plasma and placenta in PE patients. A significant increase of the protein levels of TLR-4 and NF-kB was observed in the placenta. Conclusion. The TLR4-NF-kB pathway is upregulated in PE, probably generating local and systemic inflammatory response that is followed by local and systemic oxidative damage

Efeito da transfusão de concentrado de hemácias sobre parâmetros de inflamação e estresse oxidativo em pacientes criticamente enfermos Effect of red blood cell transfusion on parameters of inflammation and oxidative stress in critically ill patients

INTRODUÇÃO: Transfusão de concentrado de hemácias é freqüentemente prescrita nas unidades de terapia intensiva. Durante muito tempo a transfusão de hemácias era vista como tendo benefícios clínicos óbvios. Entretanto nos últimos anos a prática de transfusão sanguínea tem sido examinada de uma forma mais cautelosa, levando a investigações a respeito dos benefícios transfusionais, incluindo aqui o fato de os efeitos imunomoduladores relacionados à transfusão podem aumentar o risco de morbimortalidade dos pacientes. OBJETIVOS: Avaliar o efeito da transfusão de concentrado de hemácias e sua relação com a produção de citocinas inflamatórias e dano oxidativo em pacientes criticamente enfermos admitidos em uma unidade de terapia intensiva. MÉTODOS: Foram analisados durante 6 meses, no ano de 2008, pacientes internados na unidade de terapia intenvia que realizaram transfusão de concentrado de hemácias. Foram analisados os níveis séricos pré e pós transfusionais de interleucina-6 (IL-6), proteínas carboniladas e substâncias reativas ao ácido tiobarbitúrico (TBARS). RESULTADOS: Houve diminuição dos níveis séricos de IL-6 pós-transfusionais e um aumento significativo tanto para TBARS quanto para proteínas carboniladas. No entanto não houve significância estatística entre os níveis séricos de IL-6, TBARS antes e após transfusão de concentrado de hemácias e a taxa de mortalidade. Contudo ocorreu significância da relação dos níveis pós transfusionais de proteínas carboniladas e mortalidade. CONCLUSÃO: Transfusão de concentrado de hemácias é associada a aumento dos marcadores de dano oxidativo e diminuição de IL-6 em pacientes criticamente enfermos.<br>INTRODUCTION: Red blood cell transfusions are common in intensive care units. For many years, transfusions of red blood were thought to have obvious clinical benefits. However, in recent years, the risks and benefits of blood transfusions have been examined more carefully, including the risk of increased morbidity and mortality due to transfusion-related immunomodulation effects. OBJECTIVES: To evaluate red blood cell transfusion effects and the relationship of this procedure to the production of inflammatory cytokines and oxidative damage in critically ill patients admitted to an intensive care unit. METHODS: For 6 months in 2008, we evaluated patients admitted to an intensive care unit who underwent packed red blood cell transfusions. Pre- and post-transfusion levels of interleukin-6, carbonylated proteins and thiobarbituric acid reactive substances were assessed. RESULTS: Serum post-transfusion interleukin-6 levels were reduced, and thiobarbituric acid reactive substances and carbonylated proteins were significantly increased. No statistically significant relationship was found between the levels of pre- and post-transfusion interleukin-6 and thiobarbituric acid reactive substances and the mortality rate. However, there was a significant relationship between levels of post-transfusion carbonylated proteins and mortality. CONCLUSION: Red blood cell transfusion is associated with increased oxidative damage markers and reduced interleukin-6 levels in critically ill patients

Brain and muscle redox imbalance elicited by acute ethylmalonic acid administration.

Ethylmalonic acid (EMA) accumulates in tissues and biological fluids of patients affected by short-chain acyl-CoA dehydrogenase deficiency (SCADD) and ethylmalonic encephalopathy, illnesses characterized by neurological and muscular symptoms. Considering that the mechanisms responsible for the brain and skeletal muscle damage in these diseases are poorly known, in the present work we investigated the effects of acute EMA administration on redox status parameters in cerebral cortex and skeletal muscle from 30-day-old rats. Animals received three subcutaneous injections of EMA (6 μmol/g; 90 min interval between injections) and were killed 1 h after the last administration. Control animals received saline in the same volumes. EMA administration significantly increased thiobarbituric acid-reactive substances levels in cerebral cortex and skeletal muscle, indicating increased lipid peroxidation. In addition, carbonyl content was increased in EMA-treated animal skeletal muscle when compared to the saline group. EMA administration also significantly increased 2',7'-dihydrodichlorofluorescein oxidation and superoxide production (reactive species markers), and decreased glutathione peroxidase activity in cerebral cortex, while glutathione levels were decreased only in skeletal muscle. On the other hand, respiratory chain complex I-III activity was altered by acute EMA administration neither in cerebral cortex nor in skeletal muscle. The present results show that acute EMA administration elicits oxidative stress in rat brain and skeletal muscle, suggesting that oxidative damage may be involved in the pathophysiology of the brain and muscle symptoms found in patients affected by SCADD and ethylmalonic encephalopathy

Effect of acute ethylmalonic acid (EMA) administration (6 μmol/g) on carbonyl <i>(A)</i> and sulfhydryl <i>(B)</i> content in cerebral cortex and skeletal muscle from 30-day-old rats.

<p>The experiments were performed in duplicate and the data represent mean ± standard error of the mean and are expressed in nmol. mg protein^-1 (n = 5 per group). ***<i>p</i> < 0.001 compared to control group (Student <i>t</i> test for independent samples).</p

Effect of acute ethylmalonic acid (EMA) administration (6 μmol/g) on thiobarbituric acid-reactive species (TBA-RS) levels in cerebral cortex and skeletal muscle from 30-day-old rats.

<p>The experiments were performed in duplicate and the data represent mean ± standard error of the mean and are expressed in nmol. mg protein^-1 (n = 5 per group). ***<i>p</i> < 0.001 compared to control group (Student <i>t</i> test for independent samples).</p

Effect of acute administration of ethylmalonic acid (EMA) on respiratory chain complex I-III activity in cerebral cortex and skeletal muscle of rats.

<p>Values are mean ± standard error of mean for five independent experiments (animals) per group. Data were expressed as nmol. min^-1. mg of protein^-1. No differences between groups were detected (Student’s <i>t</i> Test).</p><p>Effect of acute administration of ethylmalonic acid (EMA) on respiratory chain complex I-III activity in cerebral cortex and skeletal muscle of rats.</p

Effect of acute administration of ethylmalonic acid (EMA) on Mn-SOD and CuZn-SOD activities in cerebral cortex and skeletal muscle of rats.

<p>Values are mean ± standard error of mean for five independent experiments (animals) per group. Data were expressed as nmol. min^-1. mg of protein^-1. No differences between groups were detected (Student’s <i>t</i> Test).</p><p>Effect of acute administration of ethylmalonic acid (EMA) on Mn-SOD and CuZn-SOD activities in cerebral cortex and skeletal muscle of rats.</p

Effect of acute ethylmalonic acid (EMA) administration (6 μmol/g) on DCFH oxidation <i>(A)</i> and superoxide generation <i>(B)</i> in cerebral cortex and skeletal muscle from 30-day-old rats.

<p>The experiments were performed in duplicate and the data represent mean ± standard error of the mean and are expressed as DCFH oxidation: nmol. mg protein^-1; superoxide: nM. min^-1. mg of protein^-1 (n = 5–8 per group). *<i>p</i> < 0.05 compared to control group (Student <i>t</i> test for independent samples).</p

Treatment with cannabidiol reverses oxidative stress parameters, cognitive impairment and mortality in rats submitted to sepsis by cecal ligation and puncture

Oxidative stress plays an important role in the development of cognitive impairment in sepsis. Here we assess the effects of acute and extended administration of cannabidiol (CBD) on oxidative stress parameters in peripheral organs and in the brain, cognitive impairment, and mortality in rats submitted to sepsis by cecal ligation and perforation (CLP). To this aim, male Wistar rats underwent either sham operation or CLP. Rats subjected to CLP were treated by intraperitoneal injection with ""basic support"" and CBD (at 2.5, 5, or 10 mg/kg once or daily for 9 days after CLP) or vehicle. Six hours after CLP (early times), the rats were killed and samples from lung, liver, kidney, heart, spleen, and brain (hippocampus, striatum, and cortex) were obtained and assayed for thiobarbituric acid reactive species (TBARS) formation and protein carbonyls. On the 10th day (late times), the rats were submitted to the inhibitory avoidance task. After the test, the animals were killed and samples from lung, liver, kidney, heart, spleen, and brain (hippocampus) were obtained and assayed for TBARS formation and protein carbonyls. The acute and extended administration of CBD at different doses reduced TBARS and carbonyl levels in some organs and had no effects in others, ameliorated cognitive impairment, and significantly reduced mortality in rats submitted to CLP. Our data provide the first experimental demonstration that CBD reduces the consequences of sepsis induced by CLP in rats, by decreasing oxidative stress in peripheral organs and in the brain, improving impaired cognitive function, and decreasing mortality. (C) 2010 Elsevier B.V. All rights reserved.CNPqFAPESCUNESCCAPE