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)

The ability of carbonaceous particles (AST-120), originally developed as an enteral adsorbent of uremic toxins, to quench nitric oxide (NO) was tested. NO in solutions prepared by two methods [NO gas bubbling and NO generating system, i.e., decomposition of 1-hydroxy-2-oxo-3-(aminopropyl)-3-isopropyl-1-triazene] were determined by a NO-specific reduction of carboxy-2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide using an electron paramagnetic resonance spectrometry. NO concentrations were less in samples containing increasing concentrations of AST-120. In a separate study, nitrite concentrations in lipopolysaccharide-treated RAW264 cells were significantly less in incubation medium containing AST-120. Thus, AST-120 may be applicable as an enteral anti-NO agent.
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PMID:Quenching of nitric oxide by an oral carbonaceous adsorbent. 924 31

To evaluate the role of nitric oxide (NO) in hepatic microcirculation and liver injury during endotoxemia, we studied O2 transport in the hepatic microcirculation of endotoxin-infused rats. Rats were continuously infused with Escherichia coli lipopolysaccharide (LPS) (0.8 mg/kg/h) for 7 hours. LPS increased the plasma levels of NO2- + NO3- and aspartate transaminase (AST), and decreased the bile flow rate and hepatic adenosine triphosphate (ATP) level. Hepatic microcirculation was evaluated by two methods: reflectance spectrophotometry showed a decrease in the oxygenation of hemoglobin (Hb) in the liver, and dual-spot microspectroscopy indicated that LPS administration decreased blood velocity, the oxygenation of Hb, and O2 release from sinusoids to hepatocytes. The observed decreases in the O2 transport parameters were prominent in pericentral sinusoids. All of these phenomena were further aggravated by the administration of N(w)-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg/h) plus LPS, and by aminoguanidine (AMG) (5 mg/kg/h) plus LPS, and these could be reversed by the concomitant administration of L-arginine (L-Arg) (100 mg/kg/h). These results suggest that deterioration of hepatic oxygen transport and liver function induced by endotoxin can be ameliorated by NO.
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PMID:Role of nitric oxide in oxygen transport in rat liver sinusoids during endotoxemia. 925 43

1 Here we compared the effects of various inhibitors of the activity of protein tyrosine kinase on (i) the expression of the activity of the inducible isoform of nitric oxide (NO) synthase (iNOS) caused by endotoxin (lipopolysaccharide, LPS) in cultured macrophages, (ii) the induction of iNOS and cyclooxygenase 2 (COX-2) protein and activity in rats with endotoxaemia, and (iii) the circulatory failure and organ dysfunction caused by LPS in the anesthetized rat. 2 Activation of murine cultured macrophages with LPS (1 microgram ml-1) resulted, within 24 h, in a significant increase in nitrite (an indicator of the formation of NO) in the cell supernatant. This increase in nitrate was attenuated by the tyrphostins AG126, AG556, AG490 or AG1641 or by genistein in a dose-dependent fashion (IC50: approximately 15 microM). In contrast, tyrphostin A1 (an analogue of tyrphostin AG126) or daidzein (an analogue of genistein) had no effect on the rise in nitrite caused by LPS. 3 Administration of LPS (E. coli, 10 mg kg-1, i.v.) caused hypotension and a reduction of the pressor responses elicited by noradrenaline (NA, 1 microgram kg-1, i.v.). Pretreatment of rats with the tyrphostins AG126, AG490, AG556, AG1641 or A1 attenuated the circulatory failure caused by LPS. Although genistein attenuated the vascular hyporeactivity to NA, it did not affect the hypotension caused by LPS. Daidzein did not affect the circulatory failure caused by LPS. 4 Endotoxaemia for 360 min resulted in rises in the serum levels of (i) urea and creatinine (indicators of renal failure), (ii) alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin and gamma-glutamyl transferase (gamma GT) (indicators of liver injury/dysfunction), lipase (an indicator of pancreatic injury) as well as lactate (an indicator of tissue hypoxia). None of the tyrosine kinase inhibitors tested had a significant effect on the rise i the serum levels of urea, but the tyrphostins AG126, AG556 or A1 significantly attenuated the rises in the serum level of creatinine caused by LPS. In addition, all tyrphostins and genistein attenuated the liver injury/failure, the pancreatic injury, the hypoglycaemia and the lactic acidosis caused by LPS. In contrast, daidzein did not reduce the organ injury/dysfunction or the lactic acidosis caused by LPS. 5 Injection of LPS resulted (within 90 min) in a substantial increase in the serum level of tumor necrosis factor alpha (TNF alpha), which was attenuated by pretreatment of LPS-rats with any of the tyrphostins used. Genistein, but not daidzein, also reduced the rise in the serum levels of TNF alpha caused by LPS. Endotoxaemia for 6 h also resulted in a substantial increase in the expression of iNOS and COX-2 protein and activity in the lung, which was attenuated by pretreatment of LPS-rats with the tyrphostins AG126, AG556 or genistein, but not by daidzein. 6 Thus, tyrphostins (AG126, AG556, AG1641 or A1) and genistein, but not daidzein (inactive analogue of genistein), prevent the (i) circulatory failure, (ii) the multiple organ dysfunction (liver and pancreatic dysfunction/injury lactacidosis, hypoglycaemia), as well as (iii) the induction of iNOS and COX-2 protein and activity in rats with endotoxic shock.
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PMID:Effects of tyrphostins and genistein on the circulatory failure and organ dysfunction caused by endotoxin in the rat: a possible role for protein tyrosine kinase. 929 29

Injection of guinea pigs with a single dose of Escherichia coli lipopolysaccharide (3.2 mg/100 g) induces a reversible endotoxic shock that was evaluated by measuring plasma glucose levels and aspartate aminotransferase activity at 24 h after lipopolysaccharide injection. The hypoglycaemia and the increase in plasma aminotransferase activity observed, correlated with the alterations found during the recovery phase of endotoxic shock. When lipid peroxidation and some antioxidant systems were measured in lungs from treated animals, we only found differences in ascorbic acid content, that was decreased by 50%. Lipopolysaccharide treatment results in a depression of pulmonary phosphatidylcholine synthesis, that correlates with the surfactant deficiencies associated with respiratory illnesses in septic shock. Guinea pigs fed on a diet with a low content in ascorbic acid were more sensitive to endotoxin. In these animals we found no detectable levels of ascorbic acid in lung, whereas both vitamin E lung levels and pulmonary phosphatidylcholine synthesis were significantly decreased. Our results point out the significance of ascorbic acid in the protection against oxidative lung injury associated to endotoxaemia, and validate our shock model for further studies on the mechanisms of this pathological condition.
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PMID:Impaired phosphatidylcholine biosynthesis and ascorbic acid depletion in lung during lipopolysaccharide-induced endotoxaemia in guinea pigs. 935 41

Propagermanium is an organic germanium compound with immunopotentiating activity. We examined the hepatoprotective effect of propagermanium and its mechanism in an experimental animal model of acute liver injury induced with Corynebacterium parvum (C. parvum) and lipopolysaccharide (LPS) injection. Oral pretreatment with propagermanium decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in a dose-dependent manner. Significant attenuation of ALT and AST activity was obtained at a dose of 3 mg/kg. Administration of propagermanium also inhibited the infiltration of mononuclear cells into the liver of mice induced by C. parvum/LPS. Immunohistochemical examination revealed infiltration of the liver by CD4-, CD8-, CD11b- and Gr-1-positive cells. Propagermanium prevented CD4- and CD11b-positive cells from infiltrating the liver. In this animal model, blood cytokine levels increased rapidly after LPS injection, causing severe hepatitis. Notably, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are important mediators of the progress of liver injury. We demonstrated that propagermanium reduced IFN-gamma production by 53% at a dose of 3 mg/kg and also significantly inhibited the production of interleukin-12 (IL-12). These results indicate that propagermanium inhibits cell infiltration in the liver and cytokine production, and improves massive liver injury in C. parvum/LPS mice.
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PMID:Hepatoprotective effect of propagermanium on Corynebacterium parvum and lipopolysaccharide-induced liver injury in mice. 971 10

We investigated the effect of rebamipide, a novel antiinflammatory agent, on liver damage in a rat model of circulatory shock induced by bacterial endotoxin (E. coli lipopolysaccharide, LPS). Endotoxemia for 6 hr resulted in a 5.9-fold rise in the serum levels of nitrite (P < 0.05) with a significant rise in the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactic dehydrogenase (LDH), suggestive of liver dysfunction. The increased activities of serum ALT, AST, and LDH, but not serum nitrite were significantly inhibited by rebamipide (100 mg/kg, orally for five days). Myeloperoxidase activity in the liver was significantly elevated in the rats with endotoxemia by 2.4-fold (P < 0.05), which was also significantly inhibited by rebamipide. Upon LPS injection, serum TNF-alpha levels peaked at 1 hr after LPS (from 167.4 +/- 20.0 to 1570.0 +/- 100.0 pg/ml) and thereafter rapidly declined. The increased TNF-alpha level measured at 1 hr was significantly inhibited by pretreatment with rebamipide (100 mg/kg for five days). It is suggested that rebamipide exerts a strong protective effect on the LPS-induced liver damage through inhibition of activation of neutrophils and TNF-alpha production.
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PMID:Effect of rebamipide on liver damage and increased tumor necrosis factor in a rat model of endotoxin shock. 975 43

This study investigated whether dietary choline can prevent endotoxin shock. Female Sprague-Dawley rats fed chow or chow plus choline chloride (0.025-0.4%) for 3 days were given lipopolysaccharide (LPS) via the tail vein. Eighty-three percent and 56% of chow-fed rats survived after 2.5 or 5.0 mg/kg LPS, respectively. Choline increased survival in a dose-dependent manner, with maximal effects observed at 0.4%; this dose of choline prevented mortality completely after 2.5 or 5 mg/kg LPS. Choline also improved the microscopic appearance of the lungs and blunted increases in serum aspartate aminotransferase levels. Intracellular Ca2+ was monitored in liver and lung macrophages during LPS exposure. Ca2+ increases in macrophages from choline-fed rats were blunted by 40-60% compared with chow-fed controls. Feeding choline also blunted tumor necrosis factor-alpha production. Feeding glycine, which prevents macrophage activation via a chloride channel, in addition to choline was even more effective than feeding choline alone, suggesting that glycine and choline act via distinct sites. These data are consistent with the hypothesis that choline diminishes endotoxin shock by preventing macrophage activation.
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PMID:A choline-rich diet improves survival in a rat model of endotoxin shock. 975 19

Antioxidant action of various molds, which are traditionally used for the production of foods or alcoholic beverages in Japan, was studied in vitro and in vivo. Antioxidant action was evaluated by scavenging stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) and lipid peroxidation of rat liver microsomes. Among 40 molds, 16 species showed the DPPH scavenging action, and the molds that can scavenge the DPPH radical inhibited lipid peroxidation. The mold with the strongest action, Monascus anka, was chosen for the investigation of a protective action against liver injury of rats. When galactosamine (GalN, 400 mg/kg) or GalN plus lipopolysaccharide (LPS, 0.5 microg/kg) was given intraperitoneally to rats (Sprague-Dawley), aspartate aminotransferase (AST) and glutathione (GSH) S-transferase (GST) activities in serum were significantly increased. However, such hepatotoxicities seen in the increase in serum enzyme levels were depressed when the extract prepared from M. anka was given 1 and 15 h before the toxic insultant. Liver microsomal GST activity, which is known to be activated by oxidative stress, was increased by GalN or GaIN plus LPS treatment and the increase was also inhibited by pretreatment with the extract. Pathomorphological changes in the liver caused by GalN treatment also were prevented by the mold extract. These results indicate that the extract of M. anka has radical scavenging action and ameliorates chemically induced hepatotoxicity.
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PMID:Screening of antioxidant action of various molds and protection of Monascus anka against experimentally induced liver injuries of rats. 1018 24

Suppressive effects of naringin on lipopolysaccharide-induced tumor necrosis factor (TNF) release followed by liver injury were investigated. Intraperitoneal (i.p.) treatment with naringin prior to an intravenous (i.v.) challenge of lipopolysaccharide significantly reduced serum TNF levels in a dose-dependent manner and was the most effective when administered 60 min prior to lipopolysaccharide challenge. Treatment with naringin 3 h prior to lipopolysaccharide challenge resulted in complete protection from lipopolysaccharide lethality in D-galactosamine-sensitized mice. Histological estimation revealed that massive cell infiltration followed by severe injury developed in the livers of lipopolysaccharide-treated and D-galactosamine-treated mice unless they had been pretreated with naringin. Appearance of apoptotic cells was also found to decrease by treatment with naringin. Increases in serum levels of aspartate aminotransferase, alanine aminotransferase and creatine kinase, responsible for lipopolysaccharide-induced liver injury, blocked by naringin administration and the levels were nearly to the normal level. These results indicate that action of naringin is mediated through suppression of lipopolysaccharide-induced TNF production.
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PMID:Suppression of lipopolysaccharide-induced tumor necrosis factor-release and liver injury in mice by naringin. 1019 61

The continuous intragastric in vivo enteral feeding model in the rat developed by Tsukamoto and French has been very useful; however, it requires surgical expertise. Recently, we found that Kupffer cells isolated from rats treated only once with ethanol were sensitized to endotoxin 24 hours later. Accordingly, these experiments were designed to determine if a new, simple animal model of ethanol hepatotoxicity could be developed based on Kupffer cell sensitization. Female Wistar rats were given ethanol (5 g/kg body weight) once every 24 hours intragastrically. Livers were stained with hematoxylin-eosin to assess steatosis, inflammation, and necrosis, and tissue triglycerides, serum transaminases, and plasma endotoxin were measured. Kupffer cells were isolated 0 to 24 hours after one intragastric dose of ethanol daily, and intracellular Ca2+ ([Ca2+]i) was measured using fura-2, while tumor necrosis factor alpha (TNF-alpha) was measured by enzyme-linked immunosorbent assay. CD14 was evaluated by Western and Northern analysis. Ethanol caused steatosis, necrosis, and inflammation in only a few weeks, and after 8 weeks, serum aspartate transaminase (AST) levels were doubled. Values were similar to levels achieved in the enteral feeding model. Triglycerides were also increased significantly by ethanol as expected, and endotoxin levels were increased to 70 to 80 pg/mL. This latter increase was prevented (<20 pg/mL) by antibiotics implicating endotoxin. In isolated Kupffer cells from untreated control rats, [Ca2+]i increased to 82 +/- 7 nmol/L after addition of lipopolysaccharide (LPS) (100 ng/mL), and levels were elevated about twofold by ethanol given 24 hours earlier (174 +/- 15 nmol/L). In addition, TNF-alpha production by Kupffer cells was increased fourfold in cells isolated from rats treated with ethanol 24 hours earlier. Sterilization of the gut with antibiotics blocked all effects of ethanol on [Ca2+]i and TNF-alpha release completely. Moreover, 4 weeks after ethanol, CD14 in Kupffer cells was elevated about twofold. A new, simple chronic model of ethanol hepatotoxicity has been developed here based on sensitization of Kupffer cells to endotoxin.
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PMID:Development of a new, simple rat model of early alcohol-induced liver injury based on sensitization of Kupffer cells. 1034 8


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