Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to compare the effect of pretreatment with N-acetylcysteine (NAC) and beta -glucan (beta GLU) on inflammatory response in a rat model of sepsis. The study was performed in the animal laboratory of the Kahramanmaras Sutcu Imam University, School of Medicine. Forty rats were randomized into four groups (control, sham, NAC, and beta GLU). Control and Sham groups received saline or NAC (200 mg/kg, po) in the NAC group and beta GLU (50 mg/kg, po) in the betaGLU group via intragastric gavage once a day for 10 days and 30 min prior to surgery. Sepsis was induced by cecal ligation and puncture (CLP) in rats. In the NAC, beta GLU, and control groups, a laparotomy was performed with the CLP procedure. In the sham group, laparotomy was performed and cecum was manipulated but not ligated or perforated. TNF-alpha and IL-6 levels were significantly elevated in the control group and decreased in the NAC and beta GLU groups. IL-10 levels were significantly increased in the beta GLU group (p < .05). Superoxide dismutase and catalase levels in the liver tissue were significantly increased in the NAC and beta GLU groups, whereas superoxide dismutase levels were higher in the beta GLU pretreatment group than the NAC pretreatment group (p < 0.05). Malondialdehyde levels in the liver tissue were significantly elevated in the control group and decreased in the NAC and beta GLU groups (p < .05). Prophylactic administration of NAC or beta GLU similarly ameliorated sepsis syndrome by reduction of the proinflammatory cytokines and increase of the anti-inflammatory cytokine levels and accession of cellular antioxidants, which protect cells from oxidative stress, thereby recruiting inflammatory cells into tissue.
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PMID:Protective effects of N-acetylcysteine and beta-glucan pretreatment on oxidative stress in cecal ligation and puncture model of sepsis. 1916 Jan 31

Heart-type fatty acid-binding protein (H-FABP) is widely distributed and has been used to diagnose certain diseases. However, its alteration during infection-evoked organ dysfunction, and the potential association between leptin and it in injury or infection has not been investigated. In the current study, serum H-FABP, leptin, C-reactive protein and interleukin-1beta in the patients with pulmonary infection-induced multiple organ dysfunction were detected. Moreover, a mouse model of sepsis was established, and serum alanine transaminase, uric acid, tissue H-FABP, myeloperoxidase, superoxide dismutase activity and histological alterations in lung and intestine were investigated. Serum H-FABP and leptin increased simultaneously and significantly in the patients, and leptin alleviated pulmonary and intestinal injuries by restraining tissue H-FABP secretions in the mouse model of sepsis. Other investigated variables showed different but independent alterations. In conclusion, H-FABP represents a useful diagnostic marker for organ dysfunction, and its association with leptin will be a novel target for emergency aid.
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PMID:Heart-type fatty acid-binding protein is a useful marker for organ dysfunction and leptin alleviates sepsis-induced organ injuries by restraining its tissue levels. 1957 9

The morphological and functional integrity of the microcirculation is compromised in many cardiovascular diseases such as hypertension, diabetes, stroke, and sepsis. Angiotensin converting enzyme inhibitors (ACEi), which are known to favor bradykinin (BK) bioactivity by reducing its metabolism, may have a positive impact on preventing the microvascular structural rarefaction that occurs in these diseases. Our study was designed to test the hypothesis that BK, via B2 receptors (B2R), protects the viability of the microvascular endothelium exposed to the necrotic and apoptotic cell death inducers H(2)O(2) and LPS independently of hemodynamics. Expression (RT-PCR and radioligand binding) and functional (calcium mobilization with fura-2AM, and p42/p44MAPK and Akt phosphorylation assays) experiments revealed the presence of functional B2R in pig cerebral microvascular endothelial cells (pCMVEC). In vitro results showed that the cytocidal effects of H(2)O(2) and LPS on pCMVEC were significantly decreased by a BK pretreatment (MTT and crystal violet tests, annexin-V staining/FACS analysis), which was countered by the B2R antagonist HOE 140. BK treatment coincided with enhanced expression of the cytoprotective proteins COX-2, Bcl-2, and (Cu/Zn)SOD. Ex vivo assays on rat brain explants showed that BK impeded (by approximately 40%) H(2)O(2)-induced microvascular degeneration (lectin-FITC staining). The present study proposes a novel role for BK in microvascular endothelial protection, which may be pertinent to the complex mechanism of action of ACEi explaining their long-term beneficial effects in maintaining vascular integrity.
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PMID:Bradykinin protects against brain microvascular endothelial cell death induced by pathophysiological stimuli. 1978 24

Sepsis/multiple organ dysfunction syndrome (MODS) is a major cause of high mortality in the intensive care unit. We have recently reported that 100% oxygen treatment is beneficial to mice with zymosan-induced sterile inflammation by increasing antioxidant enzymatic activities. Yet, the use of hyperoxia is hindered by concerns that it could exacerbate organ injury by increasing free radical formation. It is believed that systemic inflammation and overproduction of reactive oxygen species (ROS) contribute to the mechanism underlying sepsis/MODS. A ROS scavenger has been proven to protect against sepsis/MODS in some animal models. Therefore, we hypothesized that ROS scavenger pretreatment might enhance the protective action of 100% oxygen treatment against zymosan-induced sterile inflammation in mice. In the present study, we showed that 100% oxygen treatment prevented the abnormal changes in serum biochemical parameters, tissue oxygenation, and organ histopathology, and improved the 14-day survival rate in zymosan-stimulated mice, indicating that 100% oxygen treatment had a protective action on sterile inflammation. We found that pretreatment with a ROS scavenger (N-acetylcysteine, vitamin C, or dimethylthiourea) abolished this protective action of 100% oxygen treatment. We also showed that 100% oxygen treatment decreased the levels of serum proinflammatory cytokines (TNF-alpha, IL-6, and high-mobility group box 1), increased the level of serum anti-inflammatory cytokine (IL-10), and upregulated the activities of serum and tissue antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) in zymosan-stimulated mice, which were reversed by the pretreatment with a ROS scavenger (N-acetylcysteine, vitamin C, or dimethylthiourea). We thus conclude that ROS scavenger pretreatment partly abolishes the protective effects of 100% oxygen treatment on sterile inflammation in mice by regulating inflammatory cytokines as well as antioxidant enzymes.
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PMID:Effects of reactive oxygen species scavenger on the protective action of 100% oxygen treatment against sterile inflammation in mice. 1978 62

The aim of this study was to evaluate the actions of the non-steroidal anti-inflammatory drug flunixin-meglumin (FM) on the changes caused by lipopolysaccharide (LPS)-induced sepsis in the rat liver. Eight groups of five adult male Wistar rats were analysed: (1) saline injected (controls), (2) FM treated with 1.1 mg/kg, (3) FM treated with 2.2 mg/kg, (4) LPS-injected (10 mg/kg), (5) LPS-injected with 1.1 mg/kg FM pretreatment, (6) LPS-injected with 2.2 mg/kg FM pretreatment, (7) LPS-injected with 1.1 mg/kg FM post-treatment and (8) LPS-injected with 2.2 mg/kg FM post-treatment. All drugs were intraperitoneally injected. The following parameters were evaluated: plasma levels of hepatic enzymes and urea, hepatic histological characteristics, antioxidant enzymes and several metabolic fluxes. The latter comprised gluconeogenesis, ureagenesis and oxygen consumption. Liver damage in LPS-induced sepsis was characterized by histological changes, increased plasma levels of alanine aminotransferase and aspartate aminotransferase (P < 0.001) and diminished gluconeogenesis (P < 0.001) and ureagenesis (P < 0.01). LPS also induced oxidative stress as evidenced by increased catalase (P < 0.05) and superoxide dismutase activities and enhanced lipid peroxidation (P < 0.001). Pretreatment of the animals with FM minimized the histological changes and normalized, in part, all enzymatic activities. Pretreatment of the animals with FM also normalized gluconeogenesis and partly restored ureagenesis (P < 0.05). These and other results show that LPS-induced sepsis may lead to severe liver damage, affecting both structure and function. Treatment with FM can be used to avoid this damage. The antioxidant properties of FM can be, partly at least, responsible for this protective action.
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PMID:Hepatic effects of flunixin-meglumin in LPS-induced sepsis. 2003 Jul 36

Multiple organ dysfunction syndrome (MODS) is one of the leading causes of death in the intensive care unit. Organ failure especially lung injury is highly associated with the mortality for MODS patients. Volatile anesthetic isoflurane (ISO) is one of the most widely used anesthetic agents, and ISO anesthesia has been reported to improve the survival rate and organ function in sepsis/MODS models. However, the application of anesthetic dose ISO in critically ill patients is limited. Compared with i.v. anesthetic pentobarbital treatment, we showed that twice inhalation of ISO at subanesthetic dose (0.7%, 0.5 minimum alveolar concentration) alleviated lung injury at 24 h after zymosan (ZY) injection and increased the 7-day survival rate from 10% to 45% in mice. We also showed that ISO exerted its protection by significantly improving the activities of superoxide dismutase and catalase in lung and serum when compared with those in pentobarbital-treated mice. The catalase inhibitor 3-amino-1, 2, 4-triazole partially abolished the protective effect of ISO in ZY-challenged mice. We conclude that subanesthetic dose ISO protects against ZY-induced generalized inflammation and its associated lung injury via enhancing the activities of antioxidant enzymes in mice, which may provide a new strategy for the treatment of critically ill patients.
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PMID:Subanesthetic dose of isoflurane protects against zymosan-induced generalized inflammation and its associated acute lung injury in mice. 2016 Jun 72

Acute endotoxemia is associated with excessive production of proinflammatory mediators by hepatic macrophages and endothelial cells, which have been implicated in liver injury and sepsis. In these studies, we analyzed the role of MSP and its receptor STK in regulating the activity of these cells. Acute endotoxemia, induced by administration of LPS (3 mg/kg) to mice, resulted in increased expression of STK mRNA and protein in liver macrophages and endothelial cells, an effect that was dependent on TLR-4. This was correlated with decreased MSP and increased pro-MSP in serum. In Kupffer cells, but not endothelial cells, MSP suppressed LPS-induced NOS-2 expression, with no effect on COX-2. LPS treatment of mice caused a rapid (within 3 h) increase in the proinflammatory proteins NOS-2, IL-1beta, and TNF-alpha, as well as TREM-1 and TREM-3 and the anti-inflammatory cytokine IL-10 in liver macrophages and endothelial cells. Whereas LPS-induced expression of proinflammatory proteins was unchanged in STK-/- mice, IL-10 expression was reduced significantly. Enzymes mediating eicosanoid biosynthesis including COX-2 and mPGES-1 also increased in macrophages and endothelial cells after LPS administration. In STK-/- mice treated with LPS, mPGES-1 expression increased, although COX-2 expression was reduced. LPS-induced up-regulation of SOD was also reduced in STK-/- mice in liver macrophages and endothelial cells. These data suggest that MSP/STK signaling plays a role in up-regulating macrophage and endothelial cell anti-inflammatory activity during hepatic inflammatory responses. This may be important in protecting the liver from tissue injury.
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PMID:Role of STK in mouse liver macrophage and endothelial cell responsiveness during acute endotoxemia. 2045 8

Lipoteichoic acid (LTA) from Staphylococcus aureus (aLTA) and from Lactobacillus plantarum LTA (pLTA) are both recognized by Toll-like receptor 2 (TLR2), but cause different stimulatory effects on the innate immune and inflammatory responses, and their underlying cellular mechanisms are unknown. In this study, comparative proteome analysis was performed using two-dimensional gel electrophoresis and mass spectrometry on protein extracts from human monocyte THP-1 cells stimulated with either aLTA or pLTA. Differentially expressed proteins might be involved in innate immunity and inflammation. Cells treated with aLTA and with pLTA showed different protein expression profiles. Of 60 identified proteins, 10 were present only in treated cells (8 in aLTA-treated only, and 2 in pLTA-treated only), 1 protein (IMPDH2) was suppressed by pLTA, and 49 were up- or down-regulated more than three-fold by aLTA- or pLTA- stimulation. Several proteins involved in immunity or inflammation, antioxidation, or RNA processing were significantly changed in expression by aLTA- or pLTA-stimulation, including cyclophilin A, HLA-B27, D-dopachrome tautomerase, Mn- SOD, hnRNP-C, PSF and KSRP. These data demonstrated that aLTA and pLTA had different effects on the protein profile of THP-1 cells. Comparison of the proteome alterations will provide candidate biomarkers for further investigation of the immunomodulatory effects of aLTA and pLTA, and the involvement of aLTA in the pathogenesis of Staphylococcus aureus sepsis.
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PMID:Protein expression changes in human monocytic THP-1 cells treated with lipoteichoic acid from Lactobacillus plantarum and Staphylococcus aureus. 2049 18

The confirmed advantageous effects of oxygen/ozone therapy in several clinical conditions stimulated experimental studies on effects of the therapy in induced septic shock. This study researches the influence of Ozone Oxidative Pre-conditioning (OOP) in unbalance between pro-oxidant and antioxidant activity generated in liver and lung during a process of sepsis. The study was conducted on male rats. Sepsis was induced by intraperitoneal injection of fecal material and pre-treatment with ozone/oxygen mixture was administered before fecal material injection. Activities of catalase, glutathione peroxide, and superoxide dismutase were measured, as well as conjugated dienes (CD) and thiobarbituric acid reactive substances (TBARS) were estimated. The results demonstrated that OOP not cause oxidative damage. It reduced levels of pro-oxidant biomarkers in lung and liver, with decreased total pro-oxidant activity and elevated total antioxidant activity from a system for diagnosis of oxidative stress in both tissues. These results suggest that OOP protected liver and lung for oxidative stress in septic shock.
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PMID:Effect of ozone pre-conditioning on redox activity in a rat model of septic shock. 2062 56

Laminarin is a tropical plant traditionally used in Chinese medicine. In this experiment, Laminarin polysaccharides were analysed using GC-MS method and result showed that the polysaccharides contained mannose (3.27%), arabinose (8.61%), glucose (4.23%), galactose (12.12%), fucose (46.93%). Laminarin polysaccharides were tested to evaluate their effect on lung oxidative stress and lipid peroxidation in rats. The animal were divided into model and polysaccharides-treated animal. Laminarin polysaccharides were administered by gavage over a 14-day period. The results indicated that Laminarin polysaccharides significantly normalized catalase (CAT) activity (P<0.01), increased glutathione peroxidase (GPx) activity (P<0.05), superoxide dismutase (SOD) activity and reduced malondialdehyde (MDA) concentrations in animal. It could be concluded that Laminarin polysaccharides appeared to be more effective in reducing sepsis-induced oxidative stress, lipid peroxidation in animal.
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PMID:Influence of laminarin polysaccahrides on oxidative damage. 2092 May 22


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