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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sepsis is commonly associated with enhanced generation of reactive oxygen metabolites, which lead to multiple organ dysfunction. The aim of this study was to examine the role of melatonin, a potent antioxidant, in protecting the intestinal and bladder tissues against damage in a rat model of sepsis. Sepsis was induced by cecal ligation and perforation (CLP) in Wistar Albino rats. Sham operated (control) and CLP group received saline or melatonin (10 mg/kg, ip) 30 minutes prior to and 6 hours after the operation. Sixteen hours after the surgery, rats were decapitated and the intestinal and urinary bladder tissues were used for contractility studies, or stored for the measurement of malondialdehyde (MDA) content -an index of lipid peroxidation-, glutathione (GSH) levels -a key antioxidant- and myeloperoxidase (MPO) activity- an index of neutrophil infiltration-. Ileal and bladder MDA levels in the CLP group were significantly increased (p < 0.001) with concomitant decreases in GSH levels (p < 0.01 - p < 0.001) when compared to the control group. Similarly, MPO activity was significantly increased (p < 0.001) in both ileum and bladder tissues. On the other hand, melatonin treatment significantly reversed (p < 0.001) the elevations in MDA and MPO levels, while reduced GSH levels were increased back to the control levels (p < 0.01 - p < 0.001). In the CLP group, the contractility of the ileal and bladder tissues decreased significantly compared with controls. Melatonin treatment of the CLP group restored these responses. In this study, CLP induced dysfunction of the ileal and bladder tissue of rats was reversed by melatonin treatment. Moreover, melatonin, as an antioxidant, abolished the elevation in lipid peroxidation products and myeloperoxidase activity, and reduction in the endogenous antioxidant glutathione and thus protected the tissues against sepsis-induced oxidative damage.
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PMID:Melatonin treatment protects against sepsis-induced functional and biochemical changes in rat ileum and urinary bladder. 1468 50

Sepsis is a generalized inflammatory response, which involves organ systems remote from the locus of the initial infectious insult, accompanied by the release of cytokines and the subsequent formation of reactive oxygen and nitrogen species. The aim of this study was to investigate the possible protective effect of octreotide (OCT), a synthetic somatostatin analogue, against sepsis-induced oxidative damage in the uterine and ovarian tissues of rats. Sepsis was induced by caecal ligation and puncture method in female Wistar albino rats. Sepsis and sham operated (control) groups received either saline or OCT (50 microg/kg, i.p.; Novartis) immediately after the operation and at 12 h. Twenty-four hours after the surgery, rats were decapitated and serum TNF-alpha levels and tissue malondialdehyde (MDA) content, glutathione (GSH) levels and myeloperoxidase (MPO) activity were determined in the uterus and ovaries. Oxidant-induced tissue fibrosis was determined by tissue collagen contents, while the extent of tissue injuries was analyzed microscopically. Sepsis increased serum TNF-alpha levels and resulted in decreased GSH levels and increased MDA levels, MPO activity and collagen contents in both the uterus and the ovaries (p<0.05-0.001) indicating the presence of the oxidative damage, as also confirmed by histological analysis. On the other hand, OCT administration reversed these oxidant responses and reduced the severity of microscopic damage (p<0.001). In conclusion, OCT protects against sepsis-induced oxidative injury of the uterine and ovarian tissues by diminishing neutrophil infiltration, an important source of oxygen free radicals. Our results suggest that OCT may be of therapeutic value in ameliorating sepsis-associated pelvic inflammation.
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PMID:Octreotide ameliorates sepsis-induced pelvic inflammation in female rats by a neutrophil-dependent mechanism. 1565 56

Sepsis leads to various organ damage and dysfunction. One of the underlying mechanisms is thought to be the oxidative damage due to the generation of free radicals. In this study, we investigated the putative protective role of beta-glucan against sepsis-induced oxidative organ damage. Sepsis was induced by caecal ligation and puncture (CLP) in Wistar albino rats. Sham operated (control) and sepsis groups received saline or beta-glucan (50 mg/kg, po) once daily for 10 days and 30 min prior to and 6 h after the CLP. Sixteen hours after the surgery, rats were decapitated and the biochemical changes were determined in the brain, diaphragm, kidney, heart, liver and lung tissues using malondialdehyde (MDA) content - an index of lipid peroxidation - glutathione (GSH) levels - a key antioxidant - and myeloperoxidase (MPO) activity - an index of neutrophil infiltration. Serum TNF-alpha levels were assessed by RIA method. Tissues were also examined under light microscope to evaluate the degree of sepsis-induced damage. The results demonstrate that sepsis significantly decreased GSH levels and increased the MDA levels and MPO activity (p<0.05-p<0.001) causing oxidative damage. Elevated plasma TNF-alpha levels in septic rats significantly reduced to control levels in beta-glucan treated rats. Since beta-glucan administration reversed these oxidant responses, it seems likely that beta-glucan protects against sepsis-induced oxidative organ injury.
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PMID:Protective effect of beta-glucan against oxidative organ injury in a rat model of sepsis. 1595 65

Lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) generation and the concomitant decline in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) were demonstrated in human monocyte-derived dendritic cells (DC). Further, their relation to the maturation of DC, characterized by the production of cytokines, up-regulation of cell surface molecules and allo-stimulatory capacity, was examined. The LPS-induced ROS generation was demonstrated using electron paramagnetic resonance spectroscopy in intact cells, and was also confirmed using laser scanning confocal microscopy. The GSH/GSSG was assesed using a glutathione assay kit. When the DC were treated with alpha-phenyl-tert-butylnitrone, the ROS generation was attenuated, but the declined GSH/GSSG was not attenuated, and only cytokine production was suppressed among the above-mentioned maturation characteristics. When the DC were treated with glutathione monoethyl ester, both the ROS generation and the declined GSH/GSSG were attenuated, and the maturation characteristics were all suppressed. These findings suggest that the LPS-induced ROS generation and the concomitant decline in GSH/GSSG occur in human monocyte-derived DC and that the former is involved in cytokine production, while the latter is involved in the up-regulation of cell surface molecules and allo-stimulatory capacity. Since the cytokine production and the allo-stimulatory capacity of DC play an important role in inflammatory and immune responses, differential regulation of the ROS generation and the declined GSH/GSSG may be useful as therapeutic tools in diseases where both responses become entangled, such as sepsis and graft-versus-host disease.
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PMID:LPS-induced ROS generation and changes in glutathione level and their relation to the maturation of human monocyte-derived dendritic cells. 1628 Jan 35

We investigated the importance of two enzymes (superoxide dismutase--SOD and glutathione peroxidase--GSH-Px) in the antioxidant defence of newborns and analysed their activity in: human colostrum and milk (from 63 mothers, after normal delivery, without complications or signs of infection), gastric fluid (from 10 breast-fed newborns, 7-28 days after birth; and from 15 artificially-fed newborns, with no signs of infection, 7-28 days after birth), and plasma (from 10 newborns, 1-28 days old, with no signs of infection, and 10 newborns, 1-28 days old, with signs of neonatal sepsis). The results of the study showed that there was statistically significant increased activity of SOD (p<0.001) in colostrum compared to mature milk. There was no statistically important difference in the activity of GSH-Px between those two samples. The activity of SOD in the gastric fluid of the artificially-fed newborns was statistically significantly lower than in the breast-fed newborns (p<0.001). The same results were found for mature mother's milk. We discovered a significant increase of SOD plasma activity in the newborns with sepsis, compared to the breast-fed newborns, with no signs of infection. The negative correlation between the activities of SOD and GSH-Px in the gastric fluid samples of the breast-fed and the artificially-fed newborns and the newborns with sepsis, showed that the activities of both enzymes were important for adequate antioxidant defence during the neonatal period. Breast-feeding with both colostrum and mature human milk is probably very important for adequate antioxidant defence in newborns.
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PMID:[Importance of breast-feeding in antioxidant defence]. 1653 93

Severe burn induces the activation of an inflammatory cascade that contributes to the development of subsequent immunosuppression, increased susceptibility to sepsis, as well as generation of reactive oxygen radicals and lipid peroxidation, leading to multiple organ failure. In the present study, we investigated whether rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand is protective against burn-induced remote organ injury. Under brief ether anaesthesia, shaved dorsum of the rats were exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath for 10s. Rosiglitazone (4 mg/kg) or saline was administered intraperitoneally immediately after and at the 12th hour of the burn. Rats were decapitated 24h after injury and the tissue samples from lung, liver, and kidney were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels, and creatinine, blood urea concentrations (BUN) were determined to assess liver and kidney function, respectively. Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and lactate dehydrogenase (LDH) were also assayed. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, and significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, serum ALT, AST and BUN levels, as well as LDH, IL-1 beta and TNF-alpha were elevated in the burn group as compared to the control group. Rosiglitazone treatment reversed all these biochemical indices. According to the findings of the present study, rosiglitazone possesses a anti-inflammatory effect that prevents burn-induced damage in remote organs and protects against organ damage.
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PMID:Rosiglitazone, a PPAR-gamma ligand, protects against burn-induced oxidative injury of remote organs. 1746 12

Selenium is an essential micronutrient for humans. Critically ill patients with Systemic Inflammatory Response Syndrome (SIRS) and Multiple Organ Dysfunction (MOD) -such as severe sepsis, trauma, severe pancreatitis and critical burns- are exposed to severe oxidative stress. These patients exhibit decreased serum Selenium and selenoenzymes like Glutathione Peroxidase and Selenoprotein P. Selenoenzymes play a major role in protecting cells against lipid peroxidation and they are involved in the inflammatory response regulation. The degree of selenium deficiency correlates with disease severity and the incidence of mortality. In the past years, some clinical trials have studied Selenium supplementation effects in critical illness with SIRS-MOD. This therapeutic strategy could improve the outcome and prognosis in critically ill patients. Few small trials have demonstrated Selenium supplementation beneficial effects, reducing the rate of infectious complications and length of hospital stay. However, no clinical trials using Selenium supplementation in high doses have yet demonstrated significant improvement in mortality. The aims of this review are to evaluate: a) Selenium metabolism, b) the role of selenoenzymes during critical illness, c) clinical studies using Selenium alone or in combination with other antioxidants in critically ill patients and d) to analyze current parenteral Selenium replacement strategies and their results. Further multicentre, well designed randomized, double blind clinical trials about Selenium supplementation in critically ill patients with SIRS and MODS are required and appear to be attractive, necessary and challenging.
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PMID:[Selenium in critically ill patients with systemic inflammatory response]. 1761 71

Sepsis is characterized by severe redox imbalance. Glutathione plays a major role in cellular defenses against oxidative and nitrosative stress. There is limited information on the response of glutathione synthesis in human sepsis. This review proposes a critical analysis of available data on potential factors affecting glutathione synthesis in sepsis. Glutathione is synthesized from its constituent amino acids--glutamate, cysteine, and glycine. Cysteine availability and the activity of the enzyme glutamate cysteine ligase are rate-limiting for glutathione synthesis. Glutathione synthetic capacity is increased in liver and other tissues during the acute phase of experimental sepsis. Potential mechanisms for glutamate cysteine ligase activation in sepsis involve a decreased ratio of reduced/oxidized glutathione as well as the effects of reactive oxygen species, nitric oxide species, proinflammatory cytokines, heat shock proteins, and physical inactivity. Glutathione synthesis can be impaired by cysteine depletion, protein-energy malnutrition, hyperglycemia, glucocorticoid at pharmacologic doses, and decreased secretion of anterior pituitary hormones (growth hormones, thyrotropin, gonadotropins), as often observed in prolonged critical illness.
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PMID:Glutathione metabolism in sepsis. 1771 14

Ischemic gut contributes to the development of sepsis and organ failure in critically ill patients. Toll-like receptors (TLRs) have been reported to mediate the pathophysiology of organ damage following ischemia/reperfusion (I/R) injury. We hypothesize that LPS, a ligand for TLR4, decreases mesenteric I/R injury-induced gut damage through tumor necrosis factor alpha (TNF-alpha) signaling. First, wild-type (WT) mice were fed with oral antibiotics for 4 weeks to deplete the intestinal commensal microflora. At week 3, drinking water was supplemented with LPS (10 microg/microL) to trigger TLRs. The intestinal mucosa was harvested for TLR4 protein, caspase 3 activity, and terminal deoxynucleotide transferase labeling assay. Second, WT and Tnfrsf1a mice received 30-min ischemia and 30-min reperfusion (30I-30R) or 30I-180R of the intestine; intestinal permeability and lipid peroxidation of the intestine were examined. Third, WT and Tnfrsf1a mice were fed with oral antibiotics with or without LPS and received 30I-180R of the intestine. The intestinal mucosa was harvested for lipid peroxidation; glutathione (GSH) level; nuclear factor kappaB (NF-kappaB) and AP-1 DNA-binding activity; Bcl-w, TNF-alpha, and CXCR2 mRNA expression; and HSP70 protein assay. Commensal depletion increased caspase 3 activity as well as villi apoptosis and decreased TLR4 expression of the intestinal mucosa. LPS increased TLR4 expression and decreased villi apoptosis. Commensal depletion augmented 30I-180R-induced intestine permeability as well as lipid peroxidation and decreased GSH level in WT mice but not in Tnfrsf1a mice. LPS decreased 30I-180R-induced intestinal permeability as well as lipid peroxidation and increased GSH level of the intestinal mucosa in WT mice but not in Tnfrsf1a mice. Commensal depletion with 30I-180R increased NF-kappaB and AP-1 DNA-binding activity, HSP70 protein expression, and decreased Bcl-w and TNF-alpha mRNA expression of the intestinal mucosa in WT mice but not in Tnfrsf1a mice. Collectively, commensal microflora induces TLR4 expression and decreases apoptosis of the intestinal mucosa. Commensal depletion enhances I/R-induced gut damage. LPS prevents I/R-induced intestinal permeability, lipid peroxidation, and decrease in GSH level. Given that the preventive effect of LPS on I/R-induced gut damage and NF-kappaB activity of the intestine is abolished in Tnfrsf1a mice, we conclude that TLR ligand decreases mesenteric I/R injury-induced gut damage through TNF-alpha signaling.
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PMID:TLR ligand decreases mesenteric ischemia and reperfusion injury-induced gut damage through TNF-alpha signaling. 1831 7

Use of metal carbonyl-based compounds capable of releasing carbon monoxide (CO) in biological systems have emerged as a potential adjunctive therapy for sepsis via their antioxidant, anti-inflammatory, and antiapoptotic effects. The role of CO in regulation of mitochondrial dysfunction and biogenesis associated with sepsis has not been investigated. In the present study, we employed a ruthenium-based water-soluble CO carrier, tricarbonylchoro(glycinato)ruthenium (II) (CORM-3), one of the novel CO-releasing molecules (CO-RMs), to test whether CO can improve cardiac mitochondrial dysfunction and survival in peritonitis-induced sepsis. Peritonitis was performed in mice by cecal ligation and perforation. Tumor necrosis factor-alpha, interleukin-10, and nitrite/nitrate plasma levels were tested to evaluate the systemic inflammatory response. Functional mitochondrial studies included determination of membrane potential, respiration, and redox status. Oxidative stress was evaluated by measurements of mitochondrial hydrogen peroxide, carbonyl protein and GSH levels. Mitochondrial biogenesis was assessed by peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha protein expression and mitochondrial DNA (mtDNA) copy number. The systemic inflammatory response elicited by peritonitis was accompanied by mitochondrial energetic metabolism deterioration and reduced PGC-1alpha protein expression. CORM-3 treatment in septic mice restored the deleterious effects of sepsis on mitochondrial membrane potential, respiratory control ratio, and energetics. It is interesting that administration of CORM-3 during sepsis elicited a mild oxidative stress response that stimulated mitochondrial biogenesis with PGC-1alpha protein expression and mtDNA copy number increases. Our results reveal that delivery of controlled amounts of CO dramatically reduced mortality in septic mice, indicating that CO-RMs could be used therapeutically to prevent organ dysfunction and death in sepsis.
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PMID:Carbon monoxide rescues mice from lethal sepsis by supporting mitochondrial energetic metabolism and activating mitochondrial biogenesis. 1919 Feb 34


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