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)

Role of platelet-activating factor (PAF) as a potential mediator of hepatic pathophysiology was investigated using a rat model of obstructive jaundice. Over a 1-wk course of bile duct ligation, a sixfold increase in tissue levels of PAF (1.57 +/- 0.43 ng/g vs. control 0.24 +/- 0.08 ng/g) occurred in the liver, whereas no change was observed in PAF levels in plasma. Concomitantly, endotoxin was detected in portal blood drawn from jaundiced rats, and antagonism of the putative effect of endotoxin by neomycin plus polymyxin B reduced local PAF concentrations in livers from jaundiced animals. Induction of neutropenia failed to alter the elevated hepatic PAF concentrations. Moreover, a large quantity of PAF was released spontaneously from Kupffer cells isolated from livers derived from jaundiced rats but not from endothelial cells or hepatocytes from the same animals. An in vitro study using cultured Kupffer cells from normal rats indicated that Kupffer cells secreted a significant amount of PAF in response to lipopolysaccharide challenge; pretreatment of cells with polymyxin B prevented this stimulated PAF release. Treatment of animals with either of two PAF receptor antagonists (BN 52021 and WEB 2170) partially prevented the increase in tissue levels of eicosanoids and O2-derived free radicals and partially alleviated liver injury as judged by the appearance of glutamate-pyruvate transaminase in the plasma of jaundiced rats. The present study indicates 1) that endogenous PAF may be an important signaling mediator for the hepatic inflammatory alterations associated with short-term bile duct ligation and 2) that the interaction of Kupffer cells with portal endotoxin is the mechanism by which PAF is produced locally.
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PMID:Role of platelet-activating factor in hepatic responses after bile duct ligation in rats. 144 33

The role of bile acids in the development of endotoxemia during obstructive jaundice was studied in rats. Endotoxin was not found in portal and peripheral plasma of control rats. The bile ducts of seven rats were ligated. On day 7 following bile duct ligation, six animals showed portal endotoxemia and five peripheral. Oral administration of sodium ursodeoxycholate reduced this frequency to 1/7 for portal plasma and 0/7 in the case of peripheral plasma. Subsequently the influence of a bile salt mixture (85% taurocholate, 15% taurodeoxycholate) on the binding and uptake of Salmonella abortus equi lipopolysaccharide by cultured rat Kupffer cells was studied. In control preparations, the percentage cell-associated lipopolysaccharide increased with time and reached a plateau after about 2 h of incubation at 37 degrees C. In the presence of 0.3, 0.6 and 1 mumol bile salts/ml the cell-associated lipopolysaccharide was about 5%, 13% and 29% lower, respectively, of that in control cultures. Tauroursodeoxycholate (1 mM) did not inhibit the lipopolysaccharide uptake by cultured rat Kupffer cells. Based on these observations, it is likely that both phenomena, i.e., (a) the low amount of bile acids in the intestines and (b) the high serum bile acid level, account for the high frequency of endotoxemia in the peripheral blood during obstructive jaundice.
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PMID:The role of bile acids in the development of endotoxemia during obstructive jaundice in the rat. 236 79

The influence of bile salts on the binding and uptake of Salmonella abortus equi lipopolysaccharide by cultured Kupffer cells was studied. In control preparations, the percentage of cell-associated lipopolysaccharide increased with time and reached a plateau after about 2 h incubation at 37 degrees C. About 1.2 micrograms lipopolysaccharide was associated with 10(6) Kupffer cells at this time interval. In the presence of 0.3, 0.6 and 1 mumol bile salts/ml the cell-associated lipopolysaccharide was respectively, about 5%, 13% and 29% lower than in control cultures. In the presence of 1 mumol bile salts/ml, the association of lipopolysaccharide to cells at 0 degrees C was about 25% lower than in controls. Preincubation of Kupffer cells with 1 mumol bile salts/ml, with or without lipopolysaccharide, did not affect cell-associated lipopolysaccharide after removal of the bile salts. The rate of secretion of radioactivity by Kupffer cells was not influenced by the presence of bile salts during the uptake or the secretion periods. Bile acids proved to inactivate lipopolysaccharide. From these observations it was concluded that low concentrations of bile salts influence the binding and uptake of lipopolysaccharide by Kupffer cells. It was, therefore, considered likely that, in patients with obstructive jaundice, the high serum bile acid level accounts for spill-over of portal lipopolysaccharide into the systemic blood.
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PMID:The role of bile acids in the reduction in lipopolysaccharide uptake by cultured rat Kupffer cells. 257 Apr 80

This study was undertaken to elucidate the effect of the intravenous administration of ursodeoxycholic acid (UDCA) on endotoxemia in rats with obstructive jaundice from the viewpoint of the biliary excretion of lipopolysaccharide (LPS) through hepatocytes. In rats with obstructive jaundice, fluorescein isothiocyanate-labeled LPS was administered via the portal vein and then its biliary excretion was examined. A significant increase in the LPS excretion was thus noticed in UDCA-treated rats at a dose of 0.1 micromol/100 g body wt. per min. In place of UDCA, sodium taurocholate at the same dose also enhanced the biliary excretion of LPS. Secondly, we also examined whether or not UDCA protects against endotoxemia. In this experiment, nonlabeled LPS was administered via the portal vein and its peripheral concentration was then measured. In UDCA-treated rats, the endotoxin concentration was significantly lower. Finally, to elucidate the effect of UDCA on Kupffer cells, serum tumor necrosis factor (TNF-alpha) was measured. But UDCA had no effect on the TNF-alpha level. These findings thus demonstrate that the intravenous administration of UDCA protects against endotoxemia by enhancing the transport of LPS across the hepatocytes from blood to bile without affecting Kupffer cells, and that this biliary excretion of LPS is dependent on bile acids.
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PMID:Protective effect of the intravenous administration of ursodeoxycholic acid against endotoxemia in rats with obstructive jaundice. 901 91

The release of cytokine by Kupffer cells during hypoxia/reoxygenation was studied in vitro in male Wistar rats with obstructive jaundice to investigate the kinetics of interleukin-8 (IL-8) release by Kupffer cells during hypoxia/reoxygenation, and to study the influence of endotoxin during the reoxygenation period. The rats were divided into two groups: one that underwent bile duct ligation (group OJ), and one that underwent a sham operation (group C). Kupffer cells were isolated by collagenase digestion and centrifugal elutriation. The cells were first subjected to hypoxia as 95% nitrogen, after which they were given reoxygenation as 95% oxygen. In addition, they were stimulated with lipopolysaccharide (LPS) 0, 1, and 10 ng/ml. In both groups, the levels of IL-8 became increased during the period of hypoxia/reoxygenation, and reoxygenation after hypoxia further intensified IL-8 production. During the period of hypoxia, the IL-8 levels in group OJ were significantly increased compared with those in group C. With the LPS challenge, there was no significant difference in IL-8 levels in either group. In conclusion, obstructive jaundice induces the activation of Kupffer cells, resulting in increased IL-8 production during hypoxia/reoxygenation.
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PMID:Cytokine release during hypoxia reoxygenation by Kupffer cells in rats with obstructive jaundice. 1048 47

The wound healing process and production of tumour necrosis factor alpha (TNF-alpha) by peritoneal cells of 7-day and 14-day obstructive jaundice (OJ) and sham-operated rats were investigated. In the study the skin wound breaking strength was measured. In addition such histological and biochemical parameters as fibroblast and endothelial cell proliferation, inflammatory cell infiltration and hydroxyproline content were evaluated in polyurethane sponge discs implanted subcutaneously into rats. TNF-alpha production by peritoneal exudate cells (PEC), both spontaneous and lipopolysaccharide (LPS)-induced was determined by a bioassay. In OJ rats the process of both early as well as late phase of healing was impaired. The breaking strength of skin wound was decreased, the fibroblast and endothelial cell proliferation and collagen deposition, as well as hydroxyproline content were diminished. In 7 day OJ the numbers of inflammatory cells in the implants were lowered with a subsequent slight increase on day 14 of OJ. The spontaneous and LPS induced TNF-alpha production by PEC were significantly higher in 7 day OJ as compared with sham-operated controls. On day 14 of OJ the LPS-induced TNF-alpha level was, in contrast, much lower and did not differ much from the spontaneous TNF-alpha production. We conclude that the impairment of wound healing in OJ results from disturbances in functioning of the immune system caused by systemic endotoxaemia.
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PMID:The impairment of wound healing process is correlated with abnormalities of TNF-alpha production by peritoneal exudate cells in obstructive jaundiced rats. 1067 46

We investigated whether rats with obstructive jaundice produced with bile duct ligation for 2 weeks are more susceptible to the additional stress of lipopolysaccharide (LPS) administration than sham-operated rats and also examined the effects of N-acetylcysteine (NAC) on LPS stimulation in rats with bile duct ligation. The effects of LPS on the mitochondrial glutathione pool and on oxidative stress of polymorphonuclear leukocytes were investigated in cholestatic rats. Serum concentrations of alpha-glutathione S-transferase showed that lipopolysaccharide stimulation caused more severe hepatocellular injury in cholestatic rats than in sham-operated rats. In addition, concentrations of mitochondrial reduced and oxidized glutathione and hepatic adenosine triphosphate showed that LPS stimulation decreased mitochondrial function more in cholestatic rats than in sham-operated rats. Intraperitoneal administration of NAC for 2 weeks significantly improved mitochondrial function and decreased hepatocellular injury. However, the oxidative stress of polymorphonuclear leukocytes that had infiltrated hepatic tissue was increased by NAC. The present results indicate that the cholestatic liver is susceptible to the additional stress of LPS, that NAC suppresses the adverse effects of LPS in cholestatic livers, and that the oxidative stress of polymorphonuclear leukocytes is not significantly involved in mitochondrial dysfunction or hepatocellular injury in this model.
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PMID:Susceptibility to lipopolysaccharide of cholestatic rat liver produced with bile duct ligation: assessments of the mitochondrial glutathione pool and the effects of N-acetylcysteine. 1087 55

Gram-negative sepsis is a serious complication for patients with obstructive jaundice. The present study was conducted to elucidate the response of hepatic microcirculation to endotoxin 2 weeks after bile duct ligation (BDL) or sham-operation in rats. Two hours after lipopolysaccharide (LPS) injection (1, 10, or 100 microg/kg, iv.), the hepatic microvasculature was examined using in vivo microscopy. BDL elicited increases in leukocytes adhering to the sinusoidal wall, swelling of sinusoidal endothelial cells as well as phagocytic activity of hepatic macrophages and a decrease in the numbers of perfused sinusoids. LPS (1, 10, 100 microg/kg) further increased leukocyte adhesion and reduced the numbers of perfused sinusoids in a dose-dependent manner. Leukocyte adhesion in response to LPS (1, 10, 100 microg/kg) in BDL rats was increased 6.1-fold, 5.9-fold, and 3.3-fold, respectively when compared with sham-operated rats. The numbers of perfused sinusoids in response to LPS (1, 10, 100 microg/kg) in BDL rats were decreased by 42%, 36%, and 45%. While 1 and 10 microg/kg LPS also elicited an increase in phagocytic activity in BDL rats when compared with sham-operated rats, the response to 100 microg/kg LPS was suppressed. LPS did not affect the numbers of swollen endothelial cell in BDL rats. The present study demonstrated that chronic biliary obstruction enhanced the hepatic microvascular response to low doses of endotoxin. This observation suggests that exaggerated hepatic microcirculatory dysfunction during sepsis contributes to the development of liver injury and a high incidence of morbidity and mortality in biliary obstruction.
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PMID:Biliary obstruction exacerbates the hepatic microvascular inflammatory response to endotoxin. 1113 8

In our experimental study, we investigated the protective effect of 3-aminobenzamide (3-AB), the poly (ADP-ribose) synthetase (PARS inhibitor), on the ileal histopathology and the apoptosis in lipopolysaccharide (LPS)-induced inflammation in rats with obstructive jaundice (OJ). We randomized 40 rats into five groups. Group 1: sham group; Group 2: OJ group; Group 3: OJ+LPS; Group 4: OJ+3-AB+LPS; Group 5: OJ+LPS+3-AB. At the fifth day; the rats were jaundiced. In Group 3; 10 mg kg(-1) LPS was injected intraperitoneally at the fifth day and then after 6h the rats were sacrificed. In Group 4; 10 mg kg(-1) 3-AB was administrated intraperitoneally at the fifth day and repeated daily for 3 days and at the eighth day, 10 mg kg(-1) LPS was injected intraperitoneally. In Group 5, 10 mg kg(-1) LPS was injected intraperitoneally at the fifth day and after 6h 10 mg kg(-1) 3-AB was administrated intraperitoneally and repeated daily for 3 days. At the eighth day, rats were sacrificed. Blood samples were taken for detection of serum MDA levels. Ileum samples were taken after relaparotomy for histopathological examination to evaluate the endotoxin-related intestinal injury and Caspase-3 apoptosis and for detection of tissue MDA and ATPase activities. There was marked destruction of villous and crypt epithelial cells and extensive apoptosis in Groups 3 and 5 in histopathological examination. In Group 4, the scores of intestinal mucosal damage and apoptotic cells were reduced significantly (P<0.05). On the other hand, the scores of intestinal mucosal damage and apoptotic cells were not improved in Group 5. After the administration of 3-AB (Group 4), serum and ileal MDA levels decreased, ileal ATPase increased as compared to Groups 1 and 2. Our study showed that 3-AB prevented the mucosal damage and apoptotic loss of intestinal epithelial cells significantly if it was administrated before LPS. However, 3-AB failed to prevent the mucosal damage and apoptotic loss of intestinal epithelial cells significantly if there was established endotoxemia in OJ.
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PMID:The effect of PARS inhibition on ileal histopathology, apoptosis and lipid peroxidation in LPS-induced obstructive jaundice. 1279 66

Morbidity and mortality rates are very high in obstructive jaundice when it is associated with sepsis and multiple organ failure. Nitric oxide (NO) formation and increased expression of inducible nitric oxide synthase (iNOS) also take place in obstructive jaundice (OJ). N-Acetylcysteine (NAC) has a beneficial effect by demonstrating anti-inflammatory activity such as inhibits cytokine expression/release, inhibiting the adhesion molecule expression and inhibiting nuclear factor kappa B (NFkappaB). The aim of this study was to investigate the effects of NAC on liver and renal tissue iNOS, and liver tissue lipid peroxidation in lipopolysaccharide (LPS) induced obstructive jaundice. We randomized 48 rats into six groups. Group A: Sham group; group B: OJ group; group C: OJ+NAC; group D: OJ+LPS (Escherichia coli LPS serotype L-2630, 100mg, Sigma) group E: OJ+NAC+LPS; group F: OJ+LPS+NAC. NAC was started subcutaneously 100mg/kg. LPS was injected intraperitoneally and then at the tenth day we sacrificed the rats. Liver malondialdehyde (MDA) increased and liver ATPase decreased in groups B-D when compared to group A. After the administration of NAC (groups C-E), liver MDA levels decreased, tissue ATPase levels increased as compared to other groups. The liver and renal tissue iNOS expression was increased in groups B, D, and F. After the administration of NAC (groups C-E) the liver and renal tissue iNOS expression were decreased. Our results indicated that NAC prevented the deleterious effects of LPS in OJ by reducing iNOS expression via lipid peroxidation in liver and renal tissue; if it was administrated before LPS. But NAC failed to prevent the iNOS expression and lipid peroxidation if there was established endotoxemia in OJ.
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PMID:The effect of N-acetylcysteine (NAC) on liver and renal tissue inducible nitric oxide synthase (iNOS) and tissue lipid peroxidation in obstructive jaundice stimulated by lipopolysaccharide (LPS). 1472 17


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