Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The immune cells, such as phagocytes and lymphocytes, which use reactive oxygen species (ROS) for carrying out many of their functions, need appropriate levels of intracellular antioxidants to avoid the harmful effect of oxidative stress. In previous studies, we have observed changes in several functions of those leukocytes from female BALB/c mice with lethal endotoxic shock caused by intraperitoneal injection of Escherichia coli 055:B5 lipopolysaccharide (LPS) (100 mg/kg), which were associated with high ROS production. In the present study, we have investigated the redox state of the above mentioned immune cells in that lethal endotoxic shock model measuring the oxidant/antioxidant balance through the following parameters: production of ROS, proinflammatory cytokine TNFalpha reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD) and catalase (CAT) activities, malonaldehyde (MDA) and transcription factor NF-kappaB expression at different times after LPS injection. The results show an increase in ROS, TNFalpha and MDA production in both cell types, being higher in macrophages than in lymphocytes. GSSG/GSH ratio was increased in both macrophages and lymphocytes after LPS injection. With respect to the activity of the antioxidant enzymes SOD and CAT were decreased in both macrophages and lymphocytes. The activation of the transcription factor NF-kappaB was stimulated in macrophages and lymphocytes. These results point out that both lymphocytes and macrophages, which are able to play an important role in host response to endotoxin, show an oxidative stress thus contributing to the pathogenesis of this septic shock.
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PMID:Immune cells redox state from mice with endotoxin-induced oxidative stress. Involvement of NF-kappaB. 1265 13

Endotoxemia causes an enhanced production of reactive oxygen radicals, which contribute to multiple organ dysfunction. When rats were given intravenous lipopolysaccharide and tested 6 h later we found that the activities of catalase and glutathione peroxidase (GSH-Px) in kidney, were acutely suppressed while in serum the levels of nitric oxide (NO), lipid peroxidation, urea nitrogen and creatinine were significantly increased, indicating the excessive production of reactive oxygen radicals and the presence of renal injury. Pretreatment of rats with Acanthopanax Radix extract administered orally for 30 days reduced the NO and lipid peroxidation levels, increased the activities of catalase and GSH-Px, and attenuated the renal dysfunction. These results suggested that scavenging of reactive oxygen radicals is part of the mechanism by which Acanthopanax Radix extract works as an effective agent in preventing multiple organ dysfunction.
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PMID:Protective effects of Acanthopanax Radix extract against endotoxemia induced by lipopolysaccharide. 1272 39

Various drugs and chemicals can cause a glutathione (GSH) depletion in the liver. Moreover, nitric oxide (NO) can be generated in response to physiological and pathological situations such as inflammation. The aim of this study was to estimate oxidative stress when primary rat hepatocytes were exposed to GSH depletion after NO production. For this purpose, cells were preincubated with lipopolysaccharide (LPS) and gamma-interferon (IFN) for 18 h in order to induce NO production by NO synthase and then L-buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, was added for 5 h. In hepatocyte cultures preincubated with LPS and IFN before BSO addition, an increase in lipid peroxidation was noted. In those cells, an elevation of iron-bound NO and a decrease in free NO led us to suggest the involvement of low-molecular-weight iron (LMW iron) in the enhancement of oxidative stress. Indeed, addition of deferiprone, a chelator of LMW iron, reduced iron-bound NO levels and the extent of oxidative stress. Moreover, an important elevation of LMW iron levels was also observed. As both, N-acetylcysteine, a GSH precursor, and N(G)-monomethyl-L-arginine, a NO synthase inhibitor, totally inhibited the elevation of LMW iron and oxidative stress, a cooperative role could be attributed to NO production and GSH depletion.
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PMID:Glutathione depletion increases nitric oxide-induced oxidative stress in primary rat hepatocyte cultures: involvement of low-molecular-weight iron. 1272 16

The aim of this work was to study the induction and secretion of interleukin 8 (IL-8) and some oxidative stress parameters after ethanol (EtOH), acetaldehyde (Ac) or lipopolysaccharide (LPS) treatment on HepG2 cells. Cells were treated with 50 mM EtOH, 175 &mgr;M Ac or 1 &mgr;g/ml of LPS. IL-8 induction and secretion were determined in the presence of the toxics, and the effect of antioxidants N-acetyl-L-cysteine and 1,1,3,3-tetramethyl-2-thiourea was evaluated. Further, the effect of adding polyclonal anti-human tumor necrosis factor alpha (TNF-alpha) and H(2)O(2) was studied, and catalase, superoxide dismutase and glutathione peroxidase activities were determined. Lipid peroxidation increased significantly only in Ac-treated cells. All toxics failed to decrease significantly the intracellular levels of reduced GSH. Catalase activity was diminished in all treatments, while other enzyme activities did not present changes. No change in peroxide production was found with any treatment. IL-8 secretion increased in Ac (41%) and in LPS (38%)-treated cells. Antioxidant and anti-TNF-alpha treatments decreased IL-8 secretion. H(2)O(2) (0.25 mM)-treated cells increased IL-8 secretion. IL-8 reverse transcriptase-polymerase chain reaction results correlated with secretion values. Our results show that Ac and LPS treatment produced an increased IL-8 induction and secretion. Oxidative stress and TNF-alpha are mediators in IL-8 response. This observation suggests that in the in vivo liver, the mechanism of ethanol-induced IL-8 production requires ethanol metabolism, and hepatocytes do not require the interaction among different populations of liver cells to respond.
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PMID:Interleukin 8 response and oxidative stress in HepG2 cells treated with ethanol, acetaldehyde or lipopolysaccharide. 1280 41

Ifosfamide, a clinically potent chemotherapeutic agent, causes the depletion of intracellular glutathione (GSH) levels in various cell types. GSH is the major intracellular reductant against oxidative stress. 4-Hydroxyifosfamide (4-OH-IF), the activated form of ifosfamide, depletes GSH levels in T cells and natural killer (NK) cells; this is accompanied by a decrease in T-cell and NK-cell function. Here we demonstrate for the first time that human monocyte-derived dendritic cells (DCs) express higher constitutive levels of GSH and are less sensitive to 4-OH-IF-induced GSH depletion than T cells and NK cells. Treatment of DCs with 4-OH-IF significantly reduced their ability to stimulate allogeneic T-cell proliferation and interferon-gamma (IFN-gamma) production. Ifosfamide also decreased DC interleukin-12p70 (IL-12p70) production after stimulation with lipopolysaccharide (LPS) and IFN-gamma. The decrease in allostimulatory capacity and in IFN-gamma and IL-12 production correlated with a decrease in intracellular GSH in the DCs. The responses could be restored by reconstituting DC GSH levels with glutathione monoethyl ester (GSH-OEt). 4-OH-IF had no inhibitory effect on the ability of DCs to present exogenously added tyrosinase peptide to tyrosinase-specific cytotoxic T lymphocytes (CTLs). These studies suggest that in cancer patients treated with ifosfamide, protection strategies based on glutathione reconstitution may enhance DC function.
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PMID:Ifosfamide impairs the allostimulatory capacity of human dendritic cells by intracellular glutathione depletion. 1285 64

Distinct functional coupling between cyclooxygenases (COXs) and specific terminal prostanoid synthases leads to phase-specific production of particular prostaglandins (PGs). In this study, we examined the coupling between COX isozymes and PGF synthase (PGFS). Co-transfection of COXs with PGFS-I belonging to the aldo-keto reductase family into HEK293 cells resulted in increased production of PGF(2alpha) only when a high concentration of exogenous arachidonic acid (AA) was supplied. However, this enzyme failed to produce PGF(2alpha) from endogenous AA, even though significant increase in PGF(2alpha) production occurred in cells transfected with COX-2 alone. This poor COX/PGFS-I coupling was likely to arise from their distinct subcellular localization. Measurement of PGF(2alpha)-synthetic enzyme activity in homogenates of several cells revealed another type of PGFS activity that was membrane-bound, glutathione (GSH)-activated, and stimulus-inducible. In vivo, membrane-bound PGFS activity was elevated in the lung of lipopolysaccharide-treated mice. Taken together, our results suggest the presence of a novel, membrane-associated form of PGFS that is stimulus-inducible and is likely to be preferentially coupled with COX-2.
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PMID:Coupling between cyclooxygenases and prostaglandin F(2alpha) synthase. Detection of an inducible, glutathione-activated, membrane-bound prostaglandin F(2alpha)-synthetic activity. 1288 Aug 69

This study was designed to investigate whether genistein may ameliorate oxidative stress and nuclear factor kappaB (NFkappaB) activation in the lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cell line. Treatment of RAW 264.7 cells with genistein significantly reduced lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in a dose-dependent manner with an IC50 of 69.4 microM. Genistein at 50 microM and 100 microM concentrations reduced thiobarbituric acid-reactive substances (TBARS) accumulation, increasing the GSH level and antioxidant enzyme activities, such as superoxide dismutase (SOD) and catalase. The specific DNA-binding activities of nuclear factor kappaB (NFkappaB) on nuclear extracts from 50 microM and 100 microM genistein treatments were significantly suppressed. These results suggest that genistein has mild antioxidant activity to suppress intracellular oxidative stress and NFkappaB activation.
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PMID:Suppressive effects of genistein on oxidative stress and NFkappaB activation in RAW 264.7 macrophages. 1451 76

Ethyl pyruvate (EP), an effective scavenger of reactive oxygen species, is also an anti-inflammatory agent in a variety of in vivo and in vitro model systems. To gain a better understanding of the molecular basis for the anti-inflammatory effects of EP, we compared the pharmacological properties of EP andN-acetyl-l-cysteine (NAC), a well studied scavenger of reactive oxygen species and a precursor for the endogenous antioxidant glutathione (GSH). The studies were performed using RAW 264.7 murine macrophage-like cells that were stimulated with lipopolysaccharide (LPS). Although EP and NAC both inhibited LPS-induced nitric oxide and interleukin (IL)-6 secretion, the former compound was considerably more potent than the latter. EP markedly inhibited inducible nitric-oxide synthase, IL-6, and IL-10 mRNA induction, whereas the effects of NAC were minimal. EP inhibited LPS-induced nuclear factor-kappaB DNA binding to a much greater extent than did NAC. Both compounds inhibited LPS-induced lipid peroxidation, but the two compounds had qualitatively different effects on cellular levels of GSH. Although NAC increased GSH levels, EP had the opposite effect. The anti-inflammatory effects of EP were partially reversed when RAW 264.7 cells were treated with a cell-permeable GSH analog, glutathione ethyl ester. These data support the view that the anti-inflammatory effects of EP are mediated, at least in part, by the ability of EP to deplete cellular GSH stores. Moreover, the findings presented here suggest that an unusual combination of biochemical effects (inhibition of lipid peroxidation and GSH depletion) might account for the anti-inflammatory effects of EP.
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PMID:Evidence that glutathione depletion is a mechanism responsible for the anti-inflammatory effects of ethyl pyruvate in cultured lipopolysaccharide-stimulated RAW 264.7 cells. 1456 76

Cold preservation and reperfusion of liver during transplantation are necessary steps in the procedure but which are also associated with damage to the organ. One aspect of this damage is thought to concern up-regulation of inflammatory markers, such as the adhesion molecule intercellular adhesion molecule 1 (ICAM-1) on target cells in the liver. This aids sequestration of activated leucocytes, which promote inflammation, by a complex sequence of events, including free radical mediated damage. We have studied changes in ICAM-1 in rat liver as a consequence of cold preservation for various times, and also after warm reperfusion during isolated liver perfusion. We have also investigated the effects of the free radical scavenging agent (reduced glutathione-GSH) on the modulation of ICAM-1 expression after cold hypoxia and reperfusion. Livers were subjected to various regimes of cold preservation and reperfusion. Liver biopsies were taken at three time points (initial baseline on liver exposure; after organ flushing and post-storage at 0, 8, 16, and 24h cold hypoxia in University of Wisconsin solution; in the same livers after 1h warm reperfusion). The tissues were processed for frozen biopsy work, and frozen sections were stained using immunohistochemical methods, for blinded scoring by an independent observer. Positive controls were obtained by exposure to endotoxin lipopolysaccharide before liver flushing. ICAM-1 expression was low in control livers (0.33+/-0.21), and increased to near maximal (2.83+/-0.17) after endotoxin exposure. ICAM-1 expression increased progressively with cold preservation, reaching values of 1.17+/-0.31 and 1.83+/-0.31 after 16 and 24h, respectively (P<0.05 and 0.02 versus controls). Warm reperfusuion increased ICAM-1 expression in all flushed groups and with longer cold preservation was close to maximal (2.67+/-0.21 after 16h and 2.98+/-0.02 after 24h; P<0.001 in both cases). Addition of the free radical scavenger GSH prevented up-regulation of ICAM-1 in livers reperfused after flushing and cold storage for up to 8h; beyond this time, ICAM-1 expression still increased, such that by 24h cold preservation and reperfusion absence (2.98+/-0.02) or presence (2.67+/-0.21) made no difference. We conclude that liver ICAM-1 expression is demonstrably increased by progressive cold preservation and reperfusion, and is only marginally affected by addition of GSH during reperfusion. The model can be used to investigate other agents which might be more successful in preventing post-storage inflammatory damage.
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PMID:Hepatic cold hypoxia and oxidative stress: implications for ICAM-1 expression and modulation by glutathione during experimental isolated liver preservation. 1458 Aug 50


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