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)

In septic patients, chronic alcohol abuse increases the incidence of the acute respiratory distress syndrome (ARDS). Because alveolar type II cell viability is critical for epithelial repair, our objective was to determine if chronic ethanol ingestion increased the sensitivity of type II cells to the inflammatory mediators upregulated during sepsis. In rats chronically fed ethanol, type II cell mitochondrial GSH was depleted, and tumor necrosis factor-alpha (TNF-alpha)-induced generation of mitochondrial reactive oxygen species (ROS) and apoptosis were potentiated. When added to the ethanol diet, the GSH precursor (-)-2-oxo-4-thiazolidinecarboxylic acid (Procysteine; Pro) but not N-acetylcysteine (NAC) normalized type II cell mitochondrial GSH. Likewise, Pro but not NAC normalized TNF-alpha-induced mitochondrial ROS and apoptosis. This suggested that chronic ethanol ingestion potentiated TNF-alpha-induced apoptosis in type II cells via mitochondrial GSH depletion. This may be particularly relevant in ARDS when type II cell viability is critical to repair of the damaged alveolar epithelium and may have important ramifications for the treatment of ARDS patients with a history of alcohol abuse.
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PMID:Chronic ethanol ingestion potentiates TNF-alpha-mediated oxidative stress and apoptosis in rat type II cells. 1143 12

Neutrophils have a dual role in sepsis-defending against infection and mediating organ failure. Because glutathione (GSH) is lower in sepsis, the hypothesis that GSH depletion might impair the migratory response of neutrophils to infection was tested. In a mouse model of polymicrobial sepsis induced by cecal ligation and puncture, GSH depletion inhibited peritoneal neutrophil infiltration, increased bacterial colonies, augmented pulmonary neutrophil infiltrate, and worsened survival. The reduced peritoneal influx of neutrophils was explained by a reduced in vivo neutrophil migration in response to locally administered chemokines and by reduced chemotactic activity and chemokine levels in peritoneal lavage fluid. Conversely, the GSH precursor N-acetyl-l-cysteine augmented neutrophil infiltration in the peritoneum but not in the lung, decreased bacterial colonies, and improved survival. Thus, migration of neutrophils to a site of infection and to a distant site is differently regulated, and optimal GSH levels are important for an efficient response to sepsis.
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PMID:Glutathione protects mice from lethal sepsis by limiting inflammation and potentiating host defense. 1193 Mar 21

The diet of industrialised countries is usually rich in amino acids, which are in part used as a source of calories. However, metabolic alterations are observed in diseased patients and a preferential retention of Sulphurated Amino Acids (SAA) occurs during the inflammatory response. Moreover, it has been demonstrated in a model of an acute sepsis phase of rats that the metabolism of Cysteine is modified. The liver converts Cysteine at a different ratio of Sulphate to Taurine (Tau) i.e. the sulphate production decreases while the Tau conversion increases. The Glutathione (GSH) concentration is greater in the liver, kidneys and other organs and the Cysteine incorporation into proteins is higher in the spleen, lungs and plasma (Acute Phase Proteins) while the Albumin level decreases. The pro-inflammatory cytokines such as Interleukin-1, Interleukin-6 and TNF- alpha are the main initiators that alter protein and amino acid metabolism. Another important phenomenon is the impairment of Methionine conversion to Cysteine during stress. For example, premature infants or AIDS patients are capable of synthesizing Cysteine from Methionine at a much lower rate. Thus, the metabolic flow through the trans-sulphuration path may be inadequate to meet the Cysteine demand under critical conditions. In this complex picture, an SAA supply may contribute to an immune system regulation.
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PMID:The regulation of sulphurated amino acid junctions: fact or fiction in the field of inflammation? 1243 3

We investigated the combined effect of glutamine (GLN) and growth hormone (GH) on bacterial translocation (BT) in sepsis. After single intraperitoneal injection of lipopolysaccharide (10 mg/kg), 48 rats were divided randomly into four groups of 12 animals each: the control group received chow orally; the GLN group received chow plus 10% GLN; GH group received chow plus GH; and the GLN/GH group received chow, 10% GLN, and GH. Twenty-four and 96 hr later, rats were sacrificed. Portal blood culture, bacterial colony counts of cultured mesenteric lymph nodes, mucosal thickness, malondialdehyde (MDA), and glutathione (GSH) levels in the gut mucosa were measured. There was no significant change of the rate of portal blood culture between all treatment groups at 24 and 96 hr. At 24 hr, the rats receiving combined treatment of GLN and GH showed lower bacterial colony counts and mucosal MDA levels than the control rats, and higher mucosal GSH levels than the control and GLN-treated rats. At 96 hr, rats treated with both GLN and GH exhibited lower bacterial colony counts and mucosal MDA levels, and higher mucosal thickness and GSH levels than control, GLN, or GH-treated rats. This study suggests that the combination of GLN and GH may synergistically reduce BT over time in sepsis.
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PMID:Combined administration of glutamine and growth hormone synergistically reduces bacterial translocation in sepsis. 1258 81

Obstructive jaundice is associated with high morbidity and mortality. Major complications such as pulmonary dysfunction, renal failure and sepsis are frequently encountered. Recent studies and observations suggest that the free oxygen radicals (FORs) produced in obstructive jaundice may play a significant role in the etiopathogenesis of acute renal failure (ARF). Thirty rats were divided into three groups, as sham, control and treatment groups containing 10 rats each. Laparatomy was performed on each animal in the control and treatment groups and common bile ducts were ligated. Common bile duct was observed but was not ligated for the rats in the sham group. Saline solution injection was begun on the first day of surgical procedure and repeated once a day during the following 5 days. The same procedure was performed with oxygen radical scavenger dimethyl sulfoxide (1.5 mg/kg/day i.p.) instead of saline in the treatment group. The rats were sacrificed on the 7th postoperative day. On the 7th postoperative day, the bilirubin, urea and creatinine levels of the control and treatment groups were significantly higher in comparison with the sham group (p < 0.01). Although there was no statistically significant difference between the bilirubin levels of the control and treatment groups (p > 0.05), the urea and creatinine levels in the treatment group were significantly lower (p < 0.01). On the 7th postoperative day, the erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels of the control and treatment groups were significantly lower than those of the sham group (p < 0.01), whereas renal and erythrocyte malondialdehyde (MDA) levels were significantly higher (p < 0.01). Although SOD and GSH-Px levels did not differ significantly between the treatment and control groups (p > 0.05), renal and erythrocyte MDA levels of the treatment group were significantly lower than those of the control group (p < 0.01). The histopathological scores were significantly higher in the control and treatment groups (p < 0.01); there was no significant difference between the control and treatment groups (p > 0.05). FORs seem to play a significant role in the etiopathogenesis of renal failure in obstructive jaundice. Antioxidant treatment may decrease oxidative damage due to FORs and may prevent renal failure.
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PMID:Role of oxygen free radical scavengers in acute renal failure complicating obstructive jaundice. 1274 May 34

Vibrio vulnificus is the leading cause of death in the United States associated with the consumption of raw seafood, particularly oysters. In epidemiological studies, primary septicemia and inflammation-mediated septic shock caused by V. vulnificus is strongly associated with liver disease, often in the context of chronic alcohol abuse. The present study was undertaken to determine whether clinical biomarkers of liver function or cellular oxidative stress are associated with peripheral blood mononuclear cell inflammatory cytokine responses to V. vulnificus. Levels of interleukin-1 beta (IL-1 beta), IL-6, IL-8, and tumor necrosis factor alpha elicited in response to V. vulnificus and measured in cell supernatants were not associated with the liver biomarkers aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or the AST/ALT ratio. In contrast, reduced glutathione (GSH) levels were associated with the release of all four cytokines (IL-1 beta [R(2) = 0.382; P = 0.006], IL-6 [R(2) = 0.393; P = 0.005], IL-8 [R(2) = 0.487; P = 0.001], and TNF-alpha [R(2) = 0.292; P = 0.021]). Those individuals with below-normal GSH levels produced significantly less proinflammatory cytokines in response to V. vulnificus. We hypothesize that persons with markers for cellular oxidative stress have increased susceptibility to V. vulnificus septicemia.
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PMID:Inflammatory cytokine response to Vibrio vulnificus elicited by peripheral blood mononuclear cells from chronic alcohol users is associated with biomarkers of cellular oxidative stress. 1281 21

Infections, sepsis and trauma lead to cellular damage of different degrees. The formation of nitrogen and reactive oxygen intermediates (NOI and ROI) play a central role in cellular damage. In addition, it is well established that the intracellular GSH content can control both radical species whereas GSH levels are controlled by the presence of cellular growth factors. The aim of the following study was to investigate the ROI and nitric oxide formation depending on the GSH levels and the presence or absence of hepatocellular growth factors. In addition, we investigated their effects on hepatocellular injury and the status of activation of the nuclear transcriptional factor NF-kappa B which is influenced by various radical forms and the cellular GSH contents. Our data clearly demonstrate that hepatocellular growth factors such as EGF and TGF alpha can increase the GSH contents and the NOx production. In addition, we found a reduction of cellular injury and NF-kappa B expression when hepatocytes were preincubated with growth factors. Taken together, we conclude that growth factors are able to protect against hepatocellular injury in experimental sepsis by increasing the cellular GSH contents either to reduce superoxide anion formation or to induce increased NO synthesis activity with subsequent increased NO production.
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PMID:[Effect of cellular growth factors on hepatocytes in experimental infection--regulation of NF-kappa B and glutathione homeostasis]. 1451 86

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


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