RESUMO
PURPOSES: The objective of this study was to evaluate the effect of supplementation with vitamin C on intestinal anastomosis healing in malnourished rats. METHODS: Male Wistar rats were divided into three groups: (1) sham, well-nourished rats that received vehicle; (2) FR+Veh, rats that were subjected to food restriction and received vehicle; and (3) FR+VC, rats that were subjected to food restriction and received vitamin C. Four days before surgery, the animals received vitamin C (100 mg/kg/day) via gavage and underwent colon resection with anastomosis in a single plane. The survival rate of rats was monitored until day 7 after surgery. Regarding anastomosis tissues, we examined intra-abdominal adhesion index, hydroxyproline content, collagen density, inflammatory parameters, and oxidative damage to proteins and lipids. RESULTS: Malnutrition decreases body weight and increases mortality; the survival rate was 90 % in group 1, 60 % in group 2, and 80 % in group 3. Vitamin C was able to increase hydroxyproline concentration and density of collagen and decrease the intra-abdominal adhesion index, as well as the infiltration of neutrophils and oxidative damage to proteins in malnourished rats compared to group treated with vehicle. CONCLUSIONS: Preoperative vitamin C supplementation can improve the intestinal anastomosis healing, biochemical alterations, and prolong survival in rats subjected to food restriction.
Assuntos
Ácido Ascórbico/uso terapêutico , Colo/cirurgia , Suplementos Nutricionais , Desnutrição/tratamento farmacológico , Cuidados Pré-Operatórios , Reto/cirurgia , Cicatrização/efeitos dos fármacos , Anastomose Cirúrgica , Animais , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/farmacologia , Peso Corporal/efeitos dos fármacos , Colágeno/metabolismo , Colo/efeitos dos fármacos , Colo/patologia , Hidroxiprolina/metabolismo , Masculino , Desnutrição/complicações , Nitratos/metabolismo , Nitritos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Ratos Wistar , Reto/efeitos dos fármacos , Reto/patologia , Aderências Teciduais/complicações , Aderências Teciduais/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismoRESUMO
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.
Assuntos
Encéfalo/metabolismo , Malonatos/administração & dosagem , Malonatos/efeitos adversos , Músculo Esquelético/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/enzimologia , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Fluoresceínas/metabolismo , Glutationa/metabolismo , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/enzimologia , Oxirredução , Carbonilação Proteica/efeitos dos fármacos , Ratos Wistar , Compostos de Sulfidrila/metabolismo , Superóxidos/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
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.
Assuntos
Inflamação/complicações , Estresse Oxidativo , Pré-Eclâmpsia/patologia , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Inflamação/sangue , Interleucina-6/sangue , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Peroxidase/metabolismo , Placenta/enzimologia , Pré-Eclâmpsia/sangue , Gravidez , Proteínas da Gravidez/metabolismo , Carbonilação Proteica , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
INTRODUCTION: The association between biomarkers of oxidative stress and the prognosis of patients with traumatic brain injury (TBI) remains inconclusive. OBJECTIVE: The objective was to investigate the association between plasma levels of lipid peroxidation (thiobarbituric acid reactive species [TBARS]) and protein oxidation (carbonyl) biomarkers and the hospital mortality of patients with severe TBI. METHODS: Plasma levels of TBARS and carbonyl were determined in 79 consecutive patients with severe TBI (Glasgow Coma Scale [GCS] ≤8) at a median of 12 hours (interquartile range [IQ] 25-75, 6.5-19.0), 30 hours (IQ 25-75, 24.7-37.0), and 70 (IQ 25-75, 55.0-78.5) hours after TBI and were compared with age- and sex-matched controls. The association between the TBARS and carbonyl levels and the hospital mortality was analyzed by multiple logistic regression analysis. RESULTS: The mean age of patients was 34.8 years. Eighty-six percent were male. The TBARS and carbonyl levels were significantly higher in patients than in controls. There was a trend (P = .09) for higher plasma levels of TBARS and carbonyl proteins at 12 hours, but not at 30 or 70 hours, after trauma in nonsurvivors than in survivors. These findings were not confirmed after the adjustments by multiple logistic regression analysis. The final model showed a higher adjusted odds ratio for death for patients with admission GCS lower than 5 (odds ratio [OR] = 4.04; 95% confidence interval [CI], 1.33-12.13; P = .01) than those with higher GCS scores. Abnormal pupils were also associated with higher mortality (OR = 3.97; 95% CI, 1.22-12.13; P = .02). There was a nonsignificant trend for association between glucose greater than or equal to 150 mm/dL in the first 12 hours and death than levels between 70 and 149 mg/dL (OR = 2.92; 95% CI, 0.96-9.02; P = .06). CONCLUSIONS: Plasma levels of TBARS and carbonyl increase significantly in the first 70 hours after severe TBI but are not independently associated with the hospital mortality.
Assuntos
Traumatismos Craniocerebrais/sangue , Traumatismos Craniocerebrais/mortalidade , Mortalidade Hospitalar , Estresse Oxidativo , Adulto , Biomarcadores , Feminino , Escala de Coma de Glasgow , Humanos , Unidades de Terapia Intensiva , Peroxidação de Lipídeos/fisiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
Reactive oxygen species and inflammation have been implicated in renal tubule cell injury. However, there is some controversy concerning whether antioxidants might attenuate oxidative damage and inflammation in humans after hypotension in the setting of critical illness. This study was a prospective, randomized, double-blinded, placebo-controlled study that included patients with hypotension. Patients were randomized to receive either N-acetylcysteine (NAC; 50 mg/kg by 4 hours followed by 100 mg/kg/d for 48 hours diluted in 5% glucose) and deferoxamine (DFX; at a single dose of 1000 mg diluted in 5% glucose) or placebo. The primary study outcome was the serum levels of markers of oxidative damage and inflammatory response. Secondary outcomes included the incidence of acute renal failure, serum creatinine at hospital discharge, intensive care unit length of stay, and length of hospital stay. Thirty patients were enrolled in the study. The use of NAC plus DFX decreased the oxidative damage parameters but not plasma interleukin-6 levels. In contrast, plasma nitrite levels increased 24 hours after NAC plus DFX administration. On analysis of secondary outcomes, it was observed that creatinine levels at hospital discharge were lower in patients receiving NAC plus DFX when compared with placebo. NAC plus DFX administration was able to decrease plasma markers of oxidative damage and creatinine levels at hospital discharge.
Assuntos
Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Desferroxamina/farmacologia , Hipotensão/tratamento farmacológico , Interleucina-6/sangue , Sideróforos/farmacologia , Injúria Renal Aguda/sangue , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/etiologia , Adulto , Idoso , Estado Terminal , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Hipotensão/sangue , Hipotensão/complicações , Masculino , Pessoa de Meia-Idade , Nitritos/sangue , Estresse Oxidativo/efeitos dos fármacosRESUMO
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.
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.
RESUMO
Sepsis is characterized by biochemical alterations in the central nervous system at early times and cognitive impairment at late times after induction in sepsis animal model. In order to understand at least in part the mechanism of disease, we have evaluated the effects of sepsis on cytokine levels in the cerebrospinal fluid (CSF); oxidative parameters; the activity of the electron transport chain enzymes; and creatine kinase (CK) activity in the brain of sepsis survivor rats 10 days after cecal ligation and perforation (CLP). Male Wistar rats underwent CLP with "basic support" or sham-operated. Ten days after surgery, the animals were killed and prefrontal cortex, cortex, hippocampus, striatum, cerebellum, and CSF were obtained. It was found a decrease in the levels of TNF-α (P = 0.001), IL-1ß (P = 0.008), IL-6 (P = 0.038), and IL-10 (P = 0.022) in the CSF; an increase in the TBARS only hippocampus (0.027); an up-regulation in the activity of complex II (P = 0.024), III (P = 0.018), and IV (P = 0.047) only in the prefrontal cortex; a decrease in the CK activity in the cerebellum (P = 0.001) and striatum (P = 0.0001), and an increase in the hippocampus (P = 0.0001) and cortex (P = 0.0001). Oxidative stress and mitochondrial alterations observed during early times in sepsis, persisted up to 10 days after surgery. The cytokines levels during the early times were found at high levels, decreasing to low levels after 10 days. In conclusion, these findings may contribute for a better comprehension of the cognitive damage in sepsis survivor rats.
Assuntos
Encéfalo/metabolismo , Metabolismo Energético/fisiologia , Mediadores da Inflamação/metabolismo , Estresse Oxidativo , Sepse/metabolismo , Sepse/fisiopatologia , Animais , Encéfalo/fisiopatologia , Creatina Quinase/metabolismo , Citocinas/metabolismo , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Humanos , Masculino , Mitocôndrias/metabolismo , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
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.
RESUMO
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 10mg/kg once or daily for 9days 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.