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)

Using the cytochrome c method, superoxide anion that is released into the hepatic sinusoid was measured after a lipopolysaccharide challenge in a liver perfusion system. Moreover, damages of epithelial cells of the hepatic sinusoid were estimated with scanning electron microscopic analysis and levels of purine nucleoside phosphorylase/GPT ratio. Lipopolysaccharide administration increased the conversion of oxidized cytochrome c into reduced cytochrome c in the perfusate, indicating that superoxide anion was formed in the hepatic sinusoid. This change was associated with increase in levels of portal tumor necrosis factor-alpha and attenuated by the simultaneous administration of superoxide dismutase. Scanning electron microscope analysis revealed that diameters of sinusoidal fenestrae increased in rats treated with lipopolysaccharide, compared with controls. Moreover, levels of purine nucleoside phosphorylase/GPT ratio was significantly increased in the liver perfusate in lipopolysaccharide-treated rats, compared with controls. Superoxide anion in hepatic sinusoid may be one of the pathogenic factors behind damages of epithelial cells of the hepatic sinusoid caused by lipopolysaccharide.
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PMID:Formation of superoxide anion in the hepatic sinusoid after lipopolysaccharide challenge. 962 90

The inhibitory effects of YM264, a selective platelet activating factor (PAF) receptor antagonist, and 2-(3-methylsulfonylamino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-( 3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide (compound 1), a neutrophil elastase inhibitor, on mortality, and pancreatic, hepatic, renal and pulmonary dysfunction were evaluated in a rat model of multiple organ failure (MOF) accompanying acute pancreatitis. MOF was produced by intraperitoneal injection of lipopolysaccharide (LPS, 30 mg/kg) in rats with cerulein-induced pancreatitis. LPS dose-dependently increased the mortality in rats with or without pancreatitis. The threshold dose which produced death in rats without pancreatitis was 30 mg/kg. This same dose evoked death in more than 40% of rats with pancreatitis. Time-course changes in serum enzyme and organ myeloperoxidase (MPO) levels were first examined in rats with induced MOF, and the results were compared with those in rats treated with only LPS or cerulein. Pancreatic weight, and serum amylase and lipase levels significantly increased in rats with cerulein-induced pancreatitis despite the presence or absence of LPS, but recovery of these pancreatic dysfunctions was slower in the group given LPS. However, serum GOT, GPT, BUN and creatinine levels were significantly elevated only in MOF rats. In the MOF rats, the MPO level in the lung was significantly elevated and arterial oxygen pressure was decreased, indicating that infiltration of neutrophils into the lung might be involved in pulmonary dysfunction. However, the MPO levels in the pancreas and kidney in the MOF rats were not remarkably different from those in normal rats. The inhibitory effects of YM264 and compound 1 on mortality and organ dysfunction were examined in this MOF model. The 24-h survival rate for rats prophylactically and therapeutically treated with an intravenous infusion of YM264 at 0.1 mg/kg h was significantly higher than that of controls. The 24-h survival rate for rats treated prophylactically by intravenous infusion of 2 mg/kg h of compound 1 was significantly higher than that of control, whereas a beneficial dose of compound 1 was 5 mg/kg h in therapeutically treated rats. Prophylactic treatment with YM264 (0.1 mg/kg h) and compound 1 (2 mg/kg h) ameliorated organ dysfunction in rats with MOF. In conclusion, pancreatic, hepatic, renal and pulmonary dysfunctions are observed in this rat MOF model. The PAF receptor antagonist and neutrophil elastase inhibitor reduce the mortality rate in rats with MOF due to their inhibitory effects on organ dysfunction, indicating that PAF and neutrophil elastase may play important roles in the development of MOF. These results in the present model are largely consistent with those in patients with MOF, indicating that this model is suited for MOF in humans and may be used as a model to test new therapeutic approaches.
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PMID:Protective effects of a PAF receptor antagonist and a neutrophil elastase inhibitor on multiple organ failure induced by cerulein plus lipopolysaccharide in rats. 975 12

Hepatoprotective effect of 6-MFA, obtained from fungus Aspergillus ochraceus ATCC 28706, was evaluated by employing three different immunological liver injury mice models. The first liver injury model was induced by injecting anti-basic liver protein (BLP) antibody into mice previously immunised with rabbit IgG (RGG). The other models were simulated by injecting antiliver specific protein (LSP) antibody or by injecting bacterial lipopolysaccharide (LPS) into mice pretreated with Corynebacterium parvum (C. parvum). 6-MFA treatment inhibited the increased transaminases (GOT and GPT) activities and showed a tendency to inhibit the histopathological changes of the liver in all the models studied. Furthermore, 6-MFA treatment inhibited deoxycholic acid induced transaminase release from cultured rat hepatocytes in vitro, but failed to affect the formation of hemolytic plaque forming cells in immunised mice spleens and hemolytic activity of guinea pig complement in immunohemolytic reaction. Our findings, therefore, suggested that the moderate hepatoprotective effect of 6-MFA could be related to it's protective effect on hepatocyte plasma membrane rather than the direct inhibitory effects on the antibody formation and/or complement activity.
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PMID:Moderate protective effect of 6-MFA, a microbial metabolite obtained from Aspergillus ochraceus on immunological liver injury in mice. 1009 25

The methanolic extract from the flowers of Tilia argentea (linden) was found to show a hepatoprotective effect against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. By bioassay-guided separation using in vitro D-GalN-induced damage to hepatocytes, five flavonol glycosides were isolated as the hepatoprotective constituents of the methanolic extract. Tiliroside, the principal flavonol glycoside, strongly inhibited serum GPT and GOT elevations at doses of 25-100 mg/kg (p.o.) in D-GalN/LPS-treated mice. By comparing the inhibitory effects of tiliroside with those of its components alone, the kaempferol 3-O-beta-D-glucopyranoside moiety was found to be essential for the activity, and its effect was suggested to depend on the inhibition of tumor necrosis factor-alpha (TNF-alpha) production, decreased sensitivity of hepatocytes to TNF-alpha, and on the protection of hepatocytes against D-GalN.
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PMID:Hepatoprotective principles from the flowers of Tilia argentea (linden): structure requirements of tiliroside and mechanisms of action. 1181 59

Lipopolysaccharide is strongly associated with septic shock, leading to multiple organ failure. It can activate monocytes and macrophages to release proinflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and nitric oxide (NO). The present experiments were designed to induce endotoxin shock by an intravenous injection of Klebsiella pneumoniae lipopolysaccharide (LPS, 10 mg/kg) in conscious rats. Arterial pressure and heart rate (HR) were continuously monitored for 48 h after LPS administration. N-Acetylcysteine was used to study its effects on organ damage. Biochemical substances were measured to reflect organ functions. Biochemical factors included blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transferase (GOT), alanine transferase (GPT), TNF-alpha, IL-1 beta, methyl guanidine (MG), and nitrites/nitrates. LPS caused significant increases in blood BUN, Cre, LDH, CPK, GOT, GPT, TNF-alpha, IL-1 beta, MG levels, and HR, as well as a decrease in mean arterial pressure and an elevation of nitrites/nitrates. N-Acetylcysteine suppressed the release of TNF-alpha, IL-1 beta, and MG, but enhanced NO production. These actions ameliorate LPS-induced organ damage in conscious rats. The beneficial effects may suggest a potential chemopreventive effect of this compound in sepsis prevention and treatment.
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PMID:N-acetylcysteine ameliorates lipopolysaccharide-induced organ damage in conscious rats. 1496 65

Dextromethorphan (DM), an antitussive agent, has been claimed to have anti-inflammatory and immunomodulatory effects in vitro. Thus, the aim of this study was to evaluate the effects of DM on sepsis induced by intravenous (i.v.) administration of lipopolysaccharide (LPS) in anesthetized Wistar rats and by intraperitoneal administration in conscious ICR mice. Results demonstrated that pretreatment with DM (1, 5 and 10 mg/kg, i.v.) significantly attenuated the deleterious hemodynamic changes (e.g., hypotension and tachycardia) in rats treated with LPS. Meanwhile, DM (5 mg/kg) significantly inhibited the elevation of plasma tumor necrosis factor-alpha and interleukin-10 levels, as well as values of GOT and GPT (as an index of liver function), and BUN and creatinine (as an index of renal function) caused by LPS. The induction of inducible NO synthase and the overproduction of NO and superoxide anions by LPS were also reduced by DM. Moreover, infiltration of neutrophils into the lungs and liver of rats 6 h after treatment with LPS was also reduced by DM. In conclusion, the beneficial effects of DM on LPS-induced sepsis result from its anti-inflammatory and antioxidant effects. Thus, DM can possibly be used as a prophylactic agent for sepsis in the future.
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PMID:Dextromethorphan prevents circulatory failure in rats with endotoxemia. 1559 70

This study addressed the question of whether thaliporphine, a phenolic aporphine alkaloid obtained from Chinese herbs and possessing antioxidant and alpha-1 adrenoceptor antagonistic activity, has protective effects in endotoxaemic rats and we attempted to elucidate the mechanisms contributing to such protective effects. Injection of rats with endotoxin (E. coli lipopolysaccharide, LPS) induced severe hypotension and tachycardia as well as vascular hyporeactivity to noradrenaline. Pretreatment of LPS-treated rats with thaliporphine attenuated the delayed hypotension significantly whilst only a higher dose (1 mg/kg) of thaliporphine decreased LPS-induced tachycardia. LPS significantly increased nitric oxide (NO.) and superoxide anion (O(2).(-)) levels, a response that was reduced by pretreatment with 1 mg/kg thaliporphine. Endotoxaemia for 240 min resulted in a bell-shaped time course for the change of serum tumour necrosis factor-alpha (TNF-alpha) level with a peak at 60 min. Pretreatment of LPS-treated rats with 1 mg/kg thaliporphine significantly reduced the serum TNF-alpha level at 60 min. In addition, LPS caused a biphasic change in blood glucose and thaliporphine attenuated the late-phase decrease in blood glucose. Endotoxaemia induced multiple organ injury in the liver, kidney and heart, as indicated by increases of aspartate aminotransferase (GOT), alanine aminotransferase (GPT), creatinine (CRE), lactate dehydrogenase (LDH) and creatine phosphate kinase muscle-brain (CKMB) levels in serum. These increases of biochemical markers and inflammatory cell infiltration into injured tissues were reduced significantly by treatment with thaliporphine. In addition, thaliporphine increased the survival rate of LPS-treated mice dose-dependently. In conclusion, our results suggest that thaliporphine could be a novel agent for attenuating endotoxin-induced circulatory failure and multiple organ injury and may increase the survival rate. These beneficial effects of thaliporphine may be attributed to the suppression of TNF-alpha, NO. and O(2).(-) production.
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PMID:Thaliporphine increases survival rate and attenuates multiple organ injury in LPS-induced endotoxaemia. 1565 98

N-acetylcysteine (NAC) is an antioxidant and cytoprotective agent with scavenging action against reactive oxygen species and inhibitory effects on pro-inflammatory cytokines. In a previous study, we found that pretreatment with NAC attenuated organ dysfunction and damage, reduced the production of free radicals, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) following endotoxemia elicited by administration of lipopolysaccharide (LPS). In the present study, we tested the effects of post-treatment with NAC on the sepsis-induced change. Post-treatment imitates clinical therapeutic regimen with administration of drug after endotoxemia. Endotoxin shock was induced by intravenous injection of Klebsiella pneumoniae LPS (10 mg/kg) in conscious rats. Mean arterial pressure (MAP) and heart rate (HR) were continuously monitored for 48 h after LPS administration. NAC was given 20 min after LPS. Measurements of biochemical substances were taken to reflect organ functions. Biochemical factors included blood urea nitrogen (BUN), creatinine (Cre), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transferase (GOT), alanine transferase (GPT), TNF-alpha, interleukin-6 (IL-6), and interleukin-10 (IL-10). LPS significantly increased blood BUN, Cre, LDH, CPK, GOT, GPT, TNF-alpha, IL-6, IL-10 levels and HR, and decreased MAP. Post-treatment with NAC diminished the decrease in MAP, increased the HR, and decreased the markers of organ injury (BUN, Cre, LDH, CPK, GOT, GPT) and inflammatory biomarkers (TNF-alpha, IL-6, IL-10) after LPS. We conclude that post-treatment with NAC suppresses the release of plasma TNF-alpha, IL-6, and IL-10 in endotoxin shock, and decreases the markers of organ injury. These beneficial effects protect against LPS-induced kidney, heart and liver damage in conscious rats. The beneficial effects may suggest a potential chemopreventive effect of this compound after sepsis.
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PMID:Post-treatment with N-acetylcysteine ameliorates endotoxin shock-induced organ damage in conscious rats. 1686 Mar 47

Dextromethorphan (DM), an anti-tussive agent, has been claimed to have anti-inflammatory and immunomodulatory effects in vitro. In our preliminary screening test, LK-4, an analog of DM, can afford more protection against circulatory failure induced by LPS than that of DM. Thus, the aim of this study was to evaluate the effects of LK-4 on sepsis induced by intravenous (i.v.) administration of lipopolysaccharide (LPS; 10 mg/kg) in anesthetized Wistar rats and survival rate by intraperitoneal administration of LPS (70 mg/kg) in conscious ICR mice. Results demonstrated that posttreatment with LK-4 (3 and 5 mg/kg, i.v.) significantly attenuated the deleterious hemodynamic changes (e.g., hypotension and tachycardia) in rats treated with LPS. Meanwhile, LK-4 (3 mg/kg) significantly inhibited the elevation of plasma tumor necrosis factor-alpha, as well as values of GOT and GPT, and BUN and creatinine caused by LPS. The induction of inducible NO synthase and the overproduction of NO and superoxide anions by LPS were also reduced by LK-4. Moreover, infiltration of neutrophils into the lungs and liver of rats 8 h after treatment with LPS was also reduced by LK-4. Furthermore, LK-4 increased the survival rate of mice insulted by toxic dose of LPS. In conclusion, the beneficial effects of LK-4 on LPS-induced sepsis result from its anti-inflammatory and anti-oxidant effects. Thus, LK-4 can be potentially used as a therapeutic agent for sepsis in the future.
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PMID:Beneficial effects of LK-4, an analog of dextromethorphan on lipopolysaccharide-induced sepsis in rats. 1709 89

Pretreatment with a low dose of bacterial endotoxin (lipopolysaccharide, LPS) caused the reduction of cytochrome P450 (CYP) enzymes and inflammatory factors which are capable of protecting the liver from a lethal LPS challenge. However, the effects of LPS pretreatment on the expression of transforming growth factor beta1 (TGFbeta1) and leptin in thioacetamide (TAA)-induced liver fibrosis remain unknown. In this study, Sprague-Dawley rats were pretreated intraperitoneally with LPS (5 mg/kg body weight) for 24 h, and subsequently treated with TAA (200 mg/kg body weight/ 3 days) for 1 month to examine the effects of LPS on TAA-injured rats. LPS pretreatment was associated with lower granulation and lower (P < 0.05) GOT/GPT than in TAA-injured rats. The LPS-pretreated group had less collagen (Sirius red histochemical staining). Semiquantitative RT-PCR showed that the levels of collagen 3 and TGFbeta1 mRNAs were lower (P < 0.05) in the liver of LPS-pretreated rats than in TAA-injured rats. TGFbetaRI mRNA in the liver of LPS-pretreated rats exceeded (P < 0.05) that in TAA-injured rats. LPS pretreatment reduced the leptin content (Western blot) below that of TAA-injured rats. These results imply that LPS pretreatment (endotoxin tolerance) alleviates the TAA-induced liver fibrosis of rats by reducing TGFbeta1 and leptin content.
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PMID:Down-regulation of TGFbeta1 and leptin ameliorates thioacetamide-induced liver injury in lipopolysaccharide-primed rats. 1762 60


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