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LPS Injection (lp + injection)
Selected AbstractsEnhancement by pyrazole of lipopolysaccharide-induced liver injury in mice: Role of cytochrome P450 2E1 and 2A5,HEPATOLOGY, Issue 1 2006Yongke Lu The mechanisms by which alcohol causes liver injury are still not certain. Either LPS or CYP2E1 are considered independent risk factors involved in alcoholic liver disease, but mutual relationships or interactions between them are unknown. In the present study, the possible synergistic action of CYP2E1 and LPS in liver injury was investigated by evaluating the effects of pyrazole (inducer of CYP2E1), Chlormethiazole (CMZ), an inhibitor of CYP2E1, and CYP2E1-knockout mice. Mice were injected with pyrazole (150 mg/kg, ip) daily for 2 days, followed by LPS injection (4 mg/kg, ip). CMZ (50mg/kg, ip) was administered 15 h before and 30 min after LPS treatment, respectively. LPS-induced liver injury was enhanced by pyrazole, as indicated by pathological changes and increases in ALT and AST, and positive TUNEL staining. LPS-induced oxidative stress was also enhanced by pyrazole as indicated by increases in 4-hydroxy-2-nonenal and 3-nitrotyrosine adduct formation. CMZ protected against the pyrazole enhanced LPS liver injury and oxidative stress. CYP2E1 but also CYP2A5 were increased by the pyrazole/LPS treatment. CMZ decreased the elevated CYP2E1 activity by 90%, but CYP2A5 activity was also lowered (30%-50%). CYP2E1-knockout mice exhibited only minor liver injury after treatment with pyrazole/LPS, but wild-type mice exhibited severe liver injury. While no CYP2E1 was present in the CYP2E1 knockout mice, CYP2A5 activity was also lower. In conclusion, induction of CYP2E1 plays an important role in the enhancement of LPS liver injury by pyrazole, but some contribution by CYP2A5 cannot be excluded. (HEPATOLOGY 2006;44:263,274.) [source] LPS-Induced Inhibition of Osteogenesis Is TNF-, Dependent in a Murine Tooth Extraction Model,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2009Nobuyoshi Tomomatsu Abstract TNF-, is a major etiologic factor of inflammatory bone diseases such as periodontitis and rheumatoid arthritis. In addition, patients with metabolic diseases such as chronic heart disease and diabetes have significantly increased plasma levels of TNF-,. Several lines of evidence show inhibition of osteoblastogenesis by TNF-, in vitro. Therefore, bone formation and osteogenesis in these patients might be inhibited because of TNF-,. However, little is known about the inhibitory role of TNF-, in bone formation/osteogenesis in vivo. The purpose of this study was to investigate the role of TNF-, in osteogenesis using a murine tooth extraction model. Lipopolysaccharide (LPS) was injected subcutaneously into the calvariae of either wildtype (WT) or TNF-,,deficient (KO) mice. The left incisor was extracted 4 days after LPS injection. The measuring area was established as the tooth socket under the mesial root of the first molar. A significant increase in serum TNF-, levels after LPS injection was observed in WT mice. The BMD of the tooth socket was significantly decreased by LPS injection 21 days after extraction in WT but not in KO mice. Histomorphometric analysis showed a significant decrease in the mineral apposition rate after LPS injection, which appeared at an early stage in WT but not in KO mice. Injection of a peptide that blocked the TNF-, signaling pathway by preventing transmission of the NF-,B signal recovered the inhibition of osteogenesis observed after LPS injection. In conclusion, TNF-, might play a major role in LPS-induced inhibition of osteogenesis under inflammatory conditions. [source] Inhibition of Caspases In Vivo Protects the Rat Liver Against Alcohol-Induced Sensitization to Bacterial LipopolysaccharideALCOHOLISM, Issue 6 2001Ion V. Deaciuc Background: The mechanisms of liver sensitization by alcohol to Gram-negative bacterial lipopolysaccharide (LPS) remain elusive. The purpose of this study was two-fold: (1) to test the hypothesis that alcohol-enhanced liver apoptosis may be a sensitizing mechanism for LPS and (2) to further characterize the liver apoptotic response to alcohol. Methods: Rats were fed a high-fat, alcohol-containing liquid diet for 14 weeks, treated with LPS (1.0 mg/kg of body weight, intravenously) or saline, followed by injection of a pan-caspase inhibitor {IDN1965;N -[(1,3-dimethylindole-2-carbonyl)-valinyl]-3-amino-4-oxo-5-fluoropentanoic acid; 10 mg/kg of body weight, intraperitoneally} or vehicle, and killed. The following parameters were assessed: plasma aspartate: 2-oxoglutarate aminotransferase activity (AST); liver histology and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) response; caspase-3, ,8, and ,9 activity; and mRNA and protein expression for two apoptosis-signaling molecules: Fas receptor and Fas ligand; and three apoptosis adaptors: Bax, Bcl-XL, and Bcl-2. Results: Alcohol-feeding-induced liver steatosis, slightly increased caspases' activity, the number of TUNEL-positive nuclei, and facilitated the LPS necrotic effect without affecting mRNA expression of apoptosis signals and adaptors. LPS induced a significant increase in AST and the number of TUNEL-positive nuclei, both effects being more pronounced in alcohol-treated rats. LPS produced hepatic necrosis only in alcohol-treated rats. LPS effects were associated with up-regulation of mRNA expression for both apoptosis adaptors and signaling molecules. IDN1965 administration 3 hr after LPS injection strongly inhibited caspases' activity, particularly that of caspase-3. IDN1965 also abolished the increase in TUNEL-positive nuclei, reversed the effect of LPS on plasma AST in alcohol-treated rats, and prevented LPS-induced necrosis. Conclusions: (1) Alcohol-enhanced liver apoptosis may not involve regulatory steps at the transcriptional level. LPS-induced liver apoptosis seems to involve transcriptional regulation of several apoptosis adaptors. Therefore, alcohol and LPS may enhance liver apoptosis through different mechanisms. (2) Alcohol-enhanced liver apoptosis precedes and may facilitate the hepatic effects of LPS. LPS superimposed on alcohol further elevates the rate of apoptosis in the liver. This may exceed the phagocytosing capacity of the liver so that all the apoptotic cells are not phagocytosed, but rather die of necrosis. [source] Hyperbaric oxygen attenuation of lipopolysaccharide-induced acute lung injury involves heme oxygenase-1ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2005T.-Y. Huang Background:, Hyperbaric oxygen (HBO) attenuates lipopolysaccharide (LPS)-induced acute lung injury. This beneficial effect of HBO involves inhibition of inducible nitric oxide synthase (iNOS) expression and subsequent nitric oxide (NO) biosynthesis. We sought to investigate the role of heme oxygenase-1 (HO-1) on this HBO inhibition of iNOS induction and acute lung injury in septic rat lungs. Methods:, Before the experiment, 72 rats were randomly allocated to receive HBO or air treatment. With or without HBO pre-treatment, the rats were further divided into the following subgroups (n = 6): (i) LPS injection, (ii) normal saline (N/S) injection, (iii) hemin (a HO-1 inducer) plus LPS, (iv) hemin alone, (v) tin protoporphyrin (SnPP; a HO-1 inhibitor) plus LPS, and (vi) SnPP alone. All rats were maintained for 6 h and then sacrificed with a high-dose pentobarbital injection. Lung injuries and relevant enzymes expression were thus assayed. Results:, Histological analysis, PMNs/alveoli ratio, and wet/dry weight ratio measurements demonstrated that LPS caused significant lung injury and HBO and/or hemin significantly attenuated this LPS-induced lung injury. Increased pulmonary iNOS expression and NO production were associated with lung injury. Induction of HO-1, by HBO and/or hemin, significantly attenuated this LPS-induced iNOS expression and acute lung injury. SnPP, on the contrary, offset the effects of HBO and worsened the LPS-induced lung injury. Conclusions:, HBO may act through inhibiting pulmonary iNOS expression to attenuate LPS-induced acute lung injury in septic rats. Furthermore, this HBO attenuation of iNOS expression involves HO-1 induction. [source] Changes in the natural abundance of 13CO2/12CO2 in breath due to lipopolysacchride-induced acute phase responseRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 23 2009Daniel E. Butz The natural abundance of carbon-13 in blood proteins increases during the cachectic state and may be a biomarker for disease status. We hypothesized a corresponding drop in the relative abundance of 13C in breath CO2. Using the lipopolysacchride (LPS)-induced endotoxemia model of the acute cachectic state, we demonstrated that the acute phase response causes shifts in the stable isotopes of carbon in exhaled CO2 (13CO2/12CO2 delta value) shortly after administration of LPS while glucocorticoid treatment does not. Mice were injected with LPS and stable isotopes of blood amino acids and carbon in exhaled CO2 were monitored. An increase in the relative isotopic mass of serum alanine, proline and threonine was observed at 3,h after LPS injection. Breath delta values began dropping immediately after administration of LPS, and were 4,5 delta values lower than those of the control animals by 2.5,h after injection. A corresponding drop in delta value was not observed with dexamethasone treatment. Thus protein synthesis during the acute phase response probably caused the fractionation of stable isotopes observed in the plasma amino acids and in exhaled breath 13CO2 delta values. The exhaled breath 13CO2 delta value may be a valuable real-time biomarker of cachexia associated with an acute phase response due to endotoxemia. Copyright © 2009 John Wiley & Sons, Ltd. [source] Release of ATP in the central nervous system during systemic inflammation: real-time measurement in the hypothalamus of conscious rabbitsTHE JOURNAL OF PHYSIOLOGY, Issue 1 2007Alexander V. Gourine Receptors for extracellular ATP (both ionotropic and metabotropic) are widely expressed in the CNS both in neurones and glia. ATP can modulate neuronal activity in many parts of the brain and contributes to the central nervous control of several physiological functions. Here we show that during the systemic inflammatory response the extracellular concentrations of ATP increase in the anterior hypothalamus and this has a profound effect on the development of the thermoregulatory febrile response. In conscious rabbits we measured ATP release in real time with novel amperometric biosensors and monitored a marked increase in the concentration of ATP (4.0 ± 0.7 ,m) in the anterior hypothalamus in response to intravenous injection of bacterial endotoxin , lipopolysaccharide (LPS). No ATP release was observed in the posterior hypothalamus. The release of ATP coincided with the development of the initial phase of the febrile response, starting 18 ± 2 min and reaching its peak 45 ± 2 min after LPS injection. Application of the ATP receptor antagonists pyridoxal-5,-phosphate-6-azophenyl-2,,4,-disulphonic acid, Brilliant Blue G or periodate oxidized ATP dialdehyde to the site of ATP release in the anterior hypothalamus markedly augmented and prolonged the febrile response. These data indicate that during the development of the systemic inflammation, ATP is released in the anterior hypothalamus to limit the magnitude and duration of fever. This release may also have a profound effect on the hypothalamic control of other physiological functions in which ATP and related purines have been implicated to play modulatory roles, such as food intake, hormone secretion, cardiovascular activity and sleep. [source] Effects of LPS and IL-6 on Oxytocin Receptor in Non-Pregnant and Pregnant Rat UterusAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2000XIN FANG PROBLEM: Little is known regarding the regulation of the timing of parturition. Recent evidence suggests an interaction between the immune system and uterine contractility in late gestation. METHOD: Pregnant rats were treated with LPS in vivo in attempts to establish a model of premature parturition induced by the pro-inflammatory response. Uterine explants were incubated in vitro to determine the effects of IL-6 on uterine synthesis of oxytocin (OT) and its receptor (OTR). RESULTS: LPS injection was quite toxic to pregnant rats and gave extremely variable results. In animals that delivered, there was a marked increase in the uterine concentrations of OTR and OTR mRNA. There was no consistent effect regarding the timing of parturition. IL-6 caused a significant increase in the concentration of OTR mRNA in uterine explants from pregnant rats but not in tissues from non-pregnant animals. CONCLUSION: Rat uterine concentrations of OTR are regulated by IL-6. Pro-inflammatory cytokines may stimulate uterine contractility in late gestation rat uterine tissues through a mechanism involving stimulation of OTR. [source] Influence of orally administered bovine lactoferrin on lipid metabolism in lipopolysaccharide-injected preruminant calvesANIMAL SCIENCE JOURNAL, Issue 3 2009Shiro KUSHIBIKI ABSTRACT The aim of this study was to investigate the influence of oral lactoferrin (LF) administration on lipid metabolism changes in calves given lipopolysaccharide (LPS). Twenty-one 4-day-old Holstein calves were divided into three groups, with each group receiving one of three oral doses of LF (0, 1, 3 g/day) for 10 consecutive days (day ,10 to day ,1). All calves were intravenously injected with LPS (50 ng/kg BW) on day 0, the day after LF treatment ended. Plasma triglyceride concentrations were lower (P < 0.05) in the LF-treated calves than in the control calves given 0 g/day of LF at 12 and 24 h after LPS injection. Plasma NEFA concentrations were elevated between 6 and 24 h after LPS treatment. At 12 h, the concentration of plasma NEFA was lower (P < 0.05) in the calves given LF 3 g/day than in the control calves. On day 0, plasma total cholesterol and phospholipid concentrations tended to be lower in the LF groups administered 1 and 3 g of LF/day than in the control group, but did not differ significantly among the groups. The plasma very-low-density and low-density lipoprotein concentrations were lower (P < 0.05) at 12, 24, and 72 h in the LF groups than in the control calves. The concentrations of plasma high-density lipoprotein tended to be lower in the LF groups than in the control group between day 0 and 96 h, though there were no significant group differences. The concentration of plasma interleukin-1, was lower (P < 0.05) in the calves fed LF 3 g/day than in the control calves at 2 and 12,48 h after LPS injection. These data suggest that LF inhibits LPS-induced alterations in lipid metabolism in preruminant calves. [source] Adult female crickets, Gryllus texensis, maintain reproductive output after repeated immune challengesPHYSIOLOGICAL ENTOMOLOGY, Issue 2 2007KELLY L. SHOEMAKER Abstract Both immunity and reproduction are thought to be energetically costly and therefore likely to make trade-offs with one another. To assess whether increasing immune system activity results in a decline in egg production, the immune system in the cricket Gryllus texensis is activated over a period of 12 days with regular injections of lipopolysaccharide (LPS) derived from Serratia marcescens, and the number of eggs laid during this time counted. Egg quality is also assessed by measuring total protein of eggs laid, fertilization and hatching success, and the weight of individual eggs laid after the series of injections. Indirect evidence suggests that LPS induces an immune response in G. texensis. However, the number of eggs produced is not affected. There is also no effect of repeated LPS injections on female weight, egg protein content, or fertilization and hatching success. Taken together, these results suggest that with food and water provided ad libitum, females can protect many aspects of fitness in the face of increased immune system activity. However, there is some evidence to suggest that large (100 ,g) doses of LPS lead to reduced female longevity, and also in egg weight that could affect offspring success. Although the possibility exists that the decline in lifespan and egg weight after high-dose injections reflects a trade-off between reproduction and immune investment, another possibility is that these doses yield nonspecific effects, or that the high-dose induces an overwhelming immune response that leads to self-damage. [source] | |||||||||||||