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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arachidonate metabolism was examined in rats with experimentally induced acute and chronic liver injuries. Acute liver injury was induced by a single administration of D-galactosamine (D-Galn) and lipopolysaccharide (LPS) or carbon tetrachloride (CCl4). Chronic liver injury was produced by several administrations of CCl4 for 5 weeks. Non-parenchymal liver cells from rats with D-Galn/LPS-induced acute liver injury produced prominently leukotriene B4 and 5-hydroxy-arachidonic acid which were hardly synthesized by the normal rat liver. No apparent changes were observed in the arachidonate metabolism of the non-parenchymal cells of the acute CCl4-injured liver. In chronic liver injury, the production of 6-ketoprostaglandin F1 alpha, a stable metabolite of prostaglandin I2, by the non-parenchymal cell fraction was significantly enhanced in contrast with the fixed amount of the other arachidonate metabolites. These results suggested the arachidonate metabolism by non-parenchymal liver cells might change according to the pathogenesis of the liver disease.
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PMID:Arachidonate metabolism in D-galactosamine or carbon tetrachloride-induced acute and chronic liver injuries in rats. 133 Jul 97

In vitro studies were performed to determine the role of metabolic bioactivation in mediating immunosuppression by CCl4. Direct addition of CCl4 to naive spleen cell cultures sensitized with either sheep erythrocytes, DNP-Ficoll or lipopolysaccharide (LPS) resulted in a marked inhibition of the antibody forming cell (AFC) response to all three of the selected antigens at 3.0 mM concentration in culture. However, this inhibition was primarily due to the direct cytotoxic effects of CCl4 on spleen cells following 3-5 days of culture in the presence of the chemical as evidenced by a decrease in cell number and viability and by the absence of selective effects on T-cell dependent humoral responses which is contradictory to the effects observed in vivo. Co-incubation of splenocytes for 1 h with primary hepatocytes, but not with subcellular metabolic activation systems, such as S9 or microsomes, enhanced the immunotoxic effects of CCl4 in vitro. Interestingly, a 3-h co-incubation of spleen cells with metabolically active hepatocytes in primary culture resulted in an even greater potentiation of the immunotoxic effects of CCl4 as determined by the T-cell dependent IgM AFC response. Conversely, under identical conditions, CCl4 did not suppress humoral responses to the polyclonal B-cell activator LPS which is in agreement with the effects produced by in vivo exposure to CCl4. It is important to emphasize that for the metabolic activation studies (i.e. co-incubation with either S9, microsomes or hepatocytes), spleen cells were washed free of CCl4 immediately following the co-incubation period. Control splenocyte cultures (i.e. no metabolic activation system) incubated in the presence of CCl4 alone at 3.0 mM over a 3-h time-period, had no effect on spleen cell function, number or viability. In agreement with our previous findings which indicate that pretreatment of mice with inducers and inhibitors of the mixed function oxygenase system prior to CCl4 administration modulated the immunotoxic effects of CCl4 in vivo, these results lead us to conclude that immunotoxicity by CCl4 requires metabolic activation.
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PMID:The role of metabolism in carbon tetrachloride-mediated immunosuppression. In vitro studies. 146 54

Cell death triggers the release into extracellular spaces of products of chromatin catabolism, particularly of DNA. A sensitive DNA assay has been used to investigate in the mouse whether the quantitation of plasma DNA may be used as an index of in vivo cytotoxicity. It has been found that toxic doses of bacterial lipopolysaccharide, HgCl2, CCl4, cyclophosphamide and hydroxyurea, are responsible for the release of extracellular DNA in plasma, in a dose dependent relationship. In conclusion, quantitation of extracellular DNA may be used for investigating in vivo cell death phenomena induced by toxic agents and drugs. Such a method could be applied to toxicological studies in animals and man.
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PMID:Quantitation of blood plasma DNA as an index of in vivo cytotoxicity. 233 Jun

The role of peptide leukotrienes (p-LTs), especially LTC4 and LTD4 in liver disease, was investigated in mice experimental liver injury models. The liver injury was induced by the injection of bacterial lipopolysaccharide (LPS) into Corynebacterium parvum pretreated mice. Carbon tetrachloride (CCl4)-induced liver injury in mice was used as a standard model. In both injury models, extensive liver parenchymal cell damage was observed by the elevation of glutamate transaminase (GOT and GPT) activity and confirmed by significant histopathological changes in the liver. Moreover, significant elevation of LTC4 in the liver was observed in both models 1 and 6 h after the onset of disease. Administration of AA-861, a selective 5-lipoxygenase inhibitor (0.5, 1, and 2 mg/kg) and LY-171883, a p-LT receptor antagonist (50 and 200 mg/kg) suppressed the elevation of serum GOT and GPT levels and histopathological changes in both experimental liver injury models. In addition, when authentic LTC4 or LTD4 was injected into the mouse, clear elevation of serum GOT and GPT and histopathological changes of the liver were observed. These results suggest that p-LTs play a role in the onset of liver diseases in mice.
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PMID:Role of peptide-leukotrienes in liver injury in mice. 257

We have tested the effects of hyperbaric oxygen on necrosis of rat liver induced by the administration of several toxins. The extent of liver necrosis was determined 24 h after the administration of the toxins by measurement of serum levels of alanine and aspartate amino-transferases and by histologic and ultrastructural analyses. Treatment with hyperbaric oxygen decreases carbon tetrachloride (CCl4)-induced necrosis in a manner dependent upon duration and pressure of oxygen exposure. Pretreatment of rats with phenobarbital diminishes this protective effect. Hyperbaric oxygen treatment before or immediately after CCl4 intoxication is protective. Loss of protection is rapid; hyperbaric oxygen treatment 6 h after CCl4 intoxication augments the liver necrosis. No delayed necrogenic effects of CCl4 are seen in the animals treated with hyperbaric oxygen immediately. Hyperbaric oxygen augments the liver necrosis induced by acetaminophen, bromobenzene, dimethylnitrosamine or thioacetamide. This augmented necrosis is averted by prolonged treatment with hyperbaric oxygen. Hyperbaric oxygen has no effect on liver injury induced by galactosamine or lipopolysaccharide. We conclude that hyperoxia decreases the hepatic necrosis induced by compounds which undergo reductive biotransformation by the cytochrome P-450 monooxygenase system; hyperoxia augments the necrosis induced by compounds which undergo oxidative biotransformation by this system. Biotransformation of toxins appears to be nonspecifically inhibited by hyperoxic exposure of long duration.
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PMID:Effect of hyperoxia on liver necrosis induced by hepatotoxins. 287 23

The effects of carbon tetrachloride (CCl4), following 7 consecutive days of exposure ip at 500, 1000, and 1500 mg/kg, were determined on murine humoral and cell-mediated immune responses, body and organ weights, spleen cell blastogenesis following mitogenic stimulation, and clinical serum parameters for liver injury. In vivo sensitization of CCl4-treated B6C3F1 mice resulted in a dose-dependent suppression of the T-dependent antibody response to sheep red blood cells (sRBC) at all doses--36, 48, and 53%, respectively. The T-independent in vivo antibody response to DNP-Ficoll was suppressed only at 1500 mg/kg, and only by approximately 16%. This dosing regimen also resulted in a significant decrease in thymus weights; however, there were no significant effects on liver, kidney, lung, or body weights. The serum chemistry profile indicated a dose-dependent increase in serum glutamic-pyruvic transaminase (SGPT) levels (34-, 47-, and 55-fold) and a non-dose-dependent increase in serum bilirubin and total protein. Serum glucose and albumin levels were unaffected. Splenocytes from mice treated with 1500 mg/kg and sensitized in vitro with antigen demonstrated a comparably suppressed antibody response to the antigens sRBC and DNP-Ficoll as observed in vivo--66 and 28% respectively. This dose of CCl4 had no effect on the in vitro antibody response to the polyclonal antigen lipopolysaccharide. The mixed lymphocyte response was dose dependently suppressed following CCl4 exposure; however, the delayed-type hypersensitivity response was unaffected. Lymphocyte blastogenesis following mitogenic stimulation with lipopolysaccharide or concanavalin A was also inhibited by CCl4 exposure. These studies demonstrate that exposure to CCl4 results in a marked suppression in both humoral and cell-mediated immune responses at concentrations which also affect the liver as evidenced by the marked increase in SGPT levels.
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PMID:Suppression of humoral and cell-mediated immune responses by carbon tetrachloride. 292 10

The carbohydrate moieties exposed on enterobacteria before and after antibody binding have been tested with fluorescent lectins. Salmonella typhimurium 395 MS (S-type) and its Rd-mutant MR10 were coated with hyperimmune anti-MS and anti-MR 10 IgG, respectively. MR 10 bacteria and Escherichia coli O86 bacteria were coated with human colostral secretory IgA (SIgA). There was a conspicuous binding of some of the lectins to untreated bacteria not always closely related to the sugar composition of the outer membrane lipopolysaccharide (LPS) or other known sugar residues. Antibody IgG and SIgA binding modified the affinity for the lectins. The binding of some lectins was reduced, presumably by masking the bacterial sugars. Antibody IgG binding to S. typhimurium MS and R 10 enhanced the affinity for RCA-I (Gal) and to a smaller extent for WGA (GlcNAc) which may be explained by exposure of IgG oligosaccharide. Antibody SIgA binding to S. typhimurium R 10 and E. coli O86 enhanced the affinity for the above lectins to a larger extent as well as for Con A (Man, Glc). The corresponding sugars N-acetylglucosamine, mannose and glucose are present in the carbohydrate chain of the secretory component as well as in IgA indicating that when SIgA antibody binds its sugar components are exposed.
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PMID:Carbohydrate exposure on salmonella and E. coli bacteria after reaction with antibody IgG and secretory IgA (SIgA) assessed with fluorescent lectins. 643 Jul 89

The survival rate for acute hepatic failure induced by Propionibacterium acnes and lipopolysaccharide (LPS) was increased when a hot water extract from the flowers of Inula britannica L. subsp. japonica Kitam. was injected into the experimental hepatitis mice, and anti-hepatitis substances could be extracted with CHCl3. The CHCl3 extract from I.britannica was fractionated and anti-hepatitis fractions IB-3-2 and IB-3-3 were obtained. IB-3-3 had the most potent anti-hepatitis activity among the fractions but further purification of the active compound was not achieved because of the low yield. IB-3-2 contained only one substance which was identified to be taraxasteryl acetate by 1H- and 13C-NMR and MS. Taraxasteryl acetate showed potent preventive activity against acute hepatic failure induced by P.acnes and LPS in a dose-dependent manner, however deacetylation and modification of the olefinic bonds significantly decreased the anti-hepatitis activity of taraxasteryl acetate. Taraxasteryl acetate also inhibited the increment of plasma transaminase on acute hepatic failure induced by carbon tetrachloride (CCl4) or D-galactosamine. From a histological study it appeared that degeneration and necrosis, which were observed in the liver from CCl4 mice, were not found in the liver cells from taraxasteryl acetate treated mice. These results indicates that taraxasteryl acetate shows preventive effects on experimental hepatitis caused by either immunologically induced injuries or hepatotoxic chemicals.
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PMID:Preventive effect of taraxasteryl acetate from Inula britannica subsp. japonica on experimental hepatitis in vivo. 1725 90

Gentiopicroside (GPS), a main bitter secoiridoid constituent of roots of Gentiana macrophylla Pall., was tested for therapeutic effects on the two hepatic injury models, the CCl4-induced and lipopolysaccharide (LPS)/bacillus Calmette-Guerin (BCG)-induced hepatitides. An increase in serum level of hepatic aminotransferases (GOT: EC 2.6.1.1. and GPT: EC 2.6.1.2.) induced by a p.o. treatment of CCl4 was suppressed by pretreatment with GPS at 30-60 mg/kg/day for 5 consecutive days. An increase of these enzymes triggered by an i.v. treatment with LPS in mice primed with bacillus Calmette-Guerin (BCG) was also inhibited by GPS pretreatment at the same dose of GPS. In the BCG/LPS model, tumor necrosis factor (TNF), a major inflammatory mediator, was increased in serum with a peak at 90-120 min, followed by an increase of serum transaminase activities. GPS treatment significantly suppressed the increase of TNF in serum at the therapeutic doses, suggesting that GPS protected against hepatitis by inhibiting the production of TNF.
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PMID:Suppression of chemically and immunologically induced hepatic injuries by gentiopicroside in mice. 799 67

Earlier studies showed that hepatotoxicant-treated experimental animals were more susceptible than controls to the lethal effects of bacterial endotoxin. The exact mechanisms of this effect were not understood. In this paper we showed that nitric oxide (.NO) was produced in whole blood and in liver tissues of rats that had been treated with a nonlethal dose of CCl4 (1.3 g/kg) followed by a low dose of lipopolysaccharide (LPS) (100 micrograms/kg). EPR spectroscopy was used in this study to detect nitrosyl-protein complexes. Hemoglobin-nitrosyl complexes were detected in both whole blood and liver. By performing analyses of EPR spectra obtained from hepatocytes exposed to .NO, we were able to identify EPR signals attributable to nitrosyl-cytochrome P420 in rat liver. We found that nitrosyl complex formation in red blood cells and liver was inhibited by treatment with NG-mono-methyl-L-arginine, suggesting enzymatic biosynthesis of .NO. A small but significant inhibition of nitrosyl complex formation by gadolinium trichloride pretreatment was found in the liver, suggesting that Kupffer cells were also involved in .NO biosynthesis, because this treatment decreased Kupffer cells. There was a synergistic effect of CCl4 and LPS on the serum levels of the hepatic enzymes aspartate aminotransferase, alanine amino-transferase, lactate dehydrogenase, and sorbitol dehydrogenase, which are indices of parenchymal cell damage. NG-Mono-methyl-L-arginine treatment increased these hepatic enzyme activities, suggesting a protective role for .NO. EPR resonances at g approximately 2.48, 2.29, and 1.91, due to low-spin cytochromes P450/P420 (FE3+), were decreased in the livers of LPS-induced rats that had been previously treated with CCl4, indicating cytochrome P450/P420 destruction or at least a change in the valence state of the cytochrome P450/P420 heme groups to Fe2+ in the presence of .NO. Because nitrosyl-cytochrome P450 is not stable, the concomitant detection of nitrosyl-cytochrome P420 (Fe2+) could account, at least in part, for the decrease of the ferric low-spin heme groups. Our novel observations of hepatic nitrosyl species suggest that .NO plays an important role during hepatic injury caused by CCl4 in hosts exposed to endotoxin.
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PMID:Nitric oxide production during endotoxic shock in carbon tetrachloride-treated rats. 807 2


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