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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pretreatment with the reactive oxygen species scavengers superoxide dismutase (SOD) and catalase or with the xanthine oxidase inhibitor allopurinol protected mice against hepatitis induced by the combined administration of lipopolysaccharide (endotoxin) and D-galactosamine. In the sera of protected animals no tumor necrosis factor (TNF alpha) was detectable in contrast to abundant amounts in the sera of injured control animals. A similar protection by the suppression of systemic TNF alpha was observed following the pretreatment of mice with polystyrene-coupled SOD prior to endotoxic challenge. Both pretreatments were ineffective when hepatitis was evoked by administration of the mediator TNF alpha instead of endotoxin. These findings indicate that the formation of extracellular reactive oxygen species is a condition needed to induce the release of TNF alpha and thus to mediate endotoxin-induced toxicity.
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PMID:A link between extracellular reactive oxygen and endotoxin-induced release of tumour necrosis factor alpha in vivo. 155 88

Tumor necrosis factor (TNF) toxicity was induced in vivo by intravenous administration of 15 micrograms of recombinant murine TNF-alpha per kg to galactosamine-sensitized mice. Within 8 h, the animals developed a fulminant hepatitis. Intravenous administration of 0.5 mg of colchicine per kg at 19 and 4 h prior to TNF challenge protected the animals against hepatitis. Lipopolysaccharide (LPS)-stimulated, bone marrow-derived macrophages from C3H/HeN mice released significant amounts of TNF in vitro. When such macrophages were intravenously given to LPS-resistant galactosamine-sensitized C3H/HeJ mice, these animals died within 24 h. Preincubation of these transferred macrophages with colchicine did not suppress the LPS-inducible TNF release from these cells. Concordantly, administration of macrophages exposed to colchicine in vitro resulted in full lethality. However, in vivo pretreatment of C3H/HeJ mice with colchicine 19 and 4 h prior to the transfer of LPS-stimulated macrophages prevented lethality. In LPS-responsive NMRI mice which had been protected against galactosamine-LPS-induced hepatitis by pretreatment with colchicine, TNF was still released into the blood. We conclude from our findings that the in vivo protection by colchicine is mediated by blocking TNF action on target cells while the effector cells of LPS toxicity, i.e., the macrophages, remain responsive.
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PMID:Colchicine prevents tumor necrosis factor-induced toxicity in vivo. 156 85

E3330 [(2E)-3-[5-(2,3-dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonyl-2- propenoic acid] is a newly synthesized hepatoprotective quinone derivative. We examined the protective effects and possible mechanism of action of E3330 in three different endotoxin (lipopolysaccharide)-induced murine hepatitis models, in which tumor necrosis factor is suggested to play a critical role in the pathogenesis. One of these models was induced by i.v. injection of lipopolysaccharide in combination with D-galactosamine to mice. Oral pretreatment with E3330 improved the survival rate and attenuated the increase in plasma aminotransferase activities of the survivors. The other two models were induced by i.v. injection of lipopolysaccharide or a mixture of D-galactosamine and lipopolysaccharide in Propionibacterium acnes-primed mice. In both of these models, tumor necrosis factor was detected in the plasma within 3 hr of the injection. Oral pretreatment with E3330 attenuated the elevation of plasma tumor necrosis factor activity and protected mice from liver injury. Furthermore, E3330 inhibited the production of tumor necrosis factor from cultured Propionibacterium acnes-elicited murine peritoneal macrophages on stimulation with lipopolysaccharide in vitro. These findings suggest that the inhibition by E3330 of tumor necrosis factor production is the major mechanism of the protective effect of E3330 in these endotoxin-mediated hepatitis models in mice.
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PMID:Protective effects of (2E)-3-[5-(2,3-dimethoxy-6-methyl-1,4- benzoquinoyl)]-2-nonyl-2-propenoic acid on endotoxin-mediated hepatitis in mice. 162 94

The rapid regenerative response of the rat liver to partial hepatectomy is associated with a decline in liver epidermal growth factor receptor numbers which implies that ligand epidermal growth factor receptor interactions maybe important in initiating and/or modulating this process. The proliferative process in toxic hepatitis (where in contrast with partial hepatectomy the majority of hepatocytes have been exposed to damaging influences) has been less widely investigated. We studied the DNA synthetic response of rat livers to toxic injury induced by a 350 or 800 mg/kg ip injection of galactosamine and that caused by 70% hepatectomy, comparing the changes in epidermal growth factor receptor status. Both resulted in down regulation of epidermal growth factor receptors, suggesting similar ligand epidermal growth factor receptor binding occurs during the proliferative response after galactosamine administration and after partial hepatectomy. In vitro studies on isolated hepatocytes showed that epidermal growth factor receptor down regulation was not a direct effect of galactosamine on hepatocyte membranes.
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PMID:Galactosamine induced hepatitis induces a reduction in hepatocyte epidermal growth factor receptors. 164 37

The pharmacokinetics, biodisposition, and neuromuscular blocking properties of 3-desacetylvecuronium were studied in 17 adult cats. Animals were divided into three groups: five cats with kidney failure induced by bilateral ligation of the renal pedicles, six cats with galactosamine-induced fulminant hepatitis, and six control cats. An intravenous bolus of 300 micrograms.kg-1 of 3-desacetylvecuronium was rapidly injected into the jugular vein. Arterial blood, urine, and bile samples were collected at regular intervals for 6 h in control cats and for 8 h in cats with kidney or liver failure. The liver was excised for analysis at the end of the experiment. In cats with renal failure, 3-desacetylvecuronium pharmacokinetic and pharmacodynamic variables did not differ from those in control cats. In cats with liver failure, plasma clearance was significantly less and mean residence time greater than in control cats (2.8 +/- 0.6 vs. 14.1 +/- 6.5 ml.kg-1.min-1 and 334 +/- 225 vs. 49 +/- 29 min, mean +/- SD, respectively). Volume of distribution at steady state in cats with liver failure and in control cats was not different. Also, in cats with liver failure, the duration of action and recovery index of 3-desacetylvecuronium was significantly greater than in control cats (168 +/- 62 vs. 82 +/- 32 min, and 39 +/- 19 vs. 10 +/- 4 min, respectively). Onset time of neuromuscular blockade was similar in all three groups. Total recovery of 3-desacetylvecuronium, for all three groups, in urine, bile, and liver was 90 +/- 11% (mean +/- SD). In control cats, 70 +/- 18% of 3-desacetylvecuronium was recovered in bile and liver and 19 +/- 14% in urine. No 3,17-bidesacetylvecuronium (a putative 3-desacetylvecuronium metabolite) was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacokinetics, neuromuscular effects, and biodisposition of 3-desacetylvecuronium (Org 7268) in cats. 167 40

Mice were fed diets with three different ratios of alpha-linolenate (18:3n-3) to linoleate (18:2n-6), and the severity of hepatitis during endotoxic shock was compared. Dietary enrichment with alpha-linolenate increased the severity of hepatitis and the mortality induced by lipopolysaccharide (LPS) in combination with D-galactosamine (GalN). Differences in the dietary alpha-linolenate/linoleate balance were mainly reflected in the levels of arachidonate and eicosapenatenoate in liver phospholipids. Pretreatment of mice with indomethacin was found to also enhance the severity of GalN/LPS-hepatitis. This indicated that cyclooxygenase products of arachidonate may suppress the development of GalN/LPS-hepatitis. The enhancement by high alpha-linolenate diets was not observed when a lethal dose of LPS in the absence of GalN was given. Our results indicate that there are pathophysiological conditions of endotoxin-induced hepatitis under which cyclooxygenase products of arachidonate play protective roles.
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PMID:Effect of dietary alpha-linolenate/linoleate balance on endotoxin-induced hepatitis in mice. 167 89

To investigate the role of neutrophils (PMNs) and PMN-dependent adhesion molecules in the pathogenesis of liver injury in a model of endotoxin shock, male ICR mice received a dose of 700 mg/kg galactosamine and 100 micrograms/kg Salmonella abortus equi endotoxin. PMNs accumulated continuously in the liver, reaching values of 446 +/- 71 PMNs/50 high-power fields at 9 h (basal value 18 +/- 7). Plasma alanine aminotransferase activities as index of parenchymal cell injury did not change up to 5 h posttreatment (basal value 35 +/- 5 U/l) but increased to 1,950 +/- 460 U/l at 9 h. The formation of glutathione disulfide (GSSG) in plasma as an index of an extracellular oxidant stress also increased only at 9 h. Pretreatment of animals with monoclonal antibodies against the CD11b and CD18 subunits of the CD11/CD18 integrin family on the surface of the PMN reduced the number of PMNs in the liver by 50% and significantly attenuated liver injury and GSSG formation. An anti-CD11a and a nonbinding control antibody were ineffective. It is concluded that PMNs are actively involved in the pathogenesis of galactosamine and endotoxin shock and that at least in part the accumulation of PMNs, the subsequent oxidant stress, and the tissue injury in this model of experimental hepatitis are CD11b/CD18 (Mac-1) dependent.
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PMID:Neutrophil-induced liver cell injury in endotoxin shock is a CD11b/CD18-dependent mechanism. 176 46

The possible involvement of interleukin-1 alpha (IL-1 alpha) in the pathogenesis of murine hepatitis model induced with galactosamine and lipopolysaccharide (LPS) was investigated. The injection of 10 ng/mouse of LPS in combination with 10 mg/mouse of galactosamine into mice induced hepatic damage at 24 hours. Treatment with anti-mouse IL-1 alpha antiserum 30 min before galactosamine/LPS injection showed a tendency to reduce the liver injury, while pretreatment with anti-mouse tumor necrosis factor-alpha (TNF) antiserum significantly protected mice from liver injury. The use of recombinant murine TNF, instead of LPS, in combination with galactosamine could elicit hepatic damage, whereas recombinant murine IL-1 alpha could not substitute for LPS. However, recombinant murine IL-1 alpha enhanced the hepatotoxic effect of recombinant murine TNF in galactosamine-sensitized mice. These results suggest that TNF plays a major role in the pathogenesis of galactosamine/LPS hepatitis in mice and that IL-1 alpha acts synergistically with TNF in this hepatitis model.
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PMID:Interleukin-1 alpha enhances hepatotoxicity of tumor necrosis factor-alpha in galactosamine-sensitized mice. 177 33

Although the shock syndrome is recognized as a form of "mediator poisoning", a plethora of details is hardly converging into a coherent concept of chronological and molecular order. As a model for organ failure in septic shock, three alternative experimental approaches with a common pathology are presented: When galactosamine-sensitized mice receive either lipopolysaccharide or leukotriene D4 or tumor necrosis factor alpha they develop fulminant hepatitis within few hours with a lethal outcome within one day. Detailed pharmacological intervention studies allow to conclude that endotoxin-induced leukotriene D4 release induces a transient ischemia by the known vasoconstrictive action of this eicosanoid. A following reperfusion/reoxygenation phase gives rise to superoxide formation which inactivates alpha 1 proteinase inhibitor. Thus a serine protease becomes active which is responsible for the processing of a monocytic tumor necrosis factor alpha precursor to be released into the circulation after proteolytic cleavage. By this sequence the final central mediator of shock and sepsis becomes systematically abundant. The concept arising from these studies reconciles previously known findings and provides a link between the role of reactive oxygen species in inflammation, the balance of proteases and antiproteases in the extracellular space and the release of the cytokine tumor necrosis factor in sepsis and shock.
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PMID:Reactive oxygen species, antiproteases, and cytokines in sepsis. 179 93

It is known that rodents challenged with a combination of galactosamine and endotoxin develop a fulminant hepatitis within several hours. Until now, no in-vitro correlate for this organ-specific lesion has been described. Here, in-vitro conditions have been developed which allow examination of lipopolysaccharide (endotoxin)-inducible cell injury to hepatocytes. Under these in-vitro conditions (RPMI 1640 supplemented with 10% calf serum, 40% oxygen tension) which require the presence of functionally intact Kupffer cells, a concentration-dependent lactate dehydrogenase release is inducible by different lipopolysaccharides in hepatocyte cultures from Fischer rats. It can be abrogated by polymyxin B. These co-cultures secreted tumor necrosis factor-alpha into the medium upon a lipopolysaccharide stimulus. The presence of a tumor necrosis factor-alpha antiserum reduced the major part of the endotoxin-inducible cytotoxicity. Similarities in vitro and in vivo of the cytotoxic potency of various endotoxin species and the different responsiveness of hepatocytes from two different rat strains support that this co-culture system might be useful for studying endotoxin-inducible lesions in vitro.
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PMID:Endotoxin-inducible cytotoxicity in liver cell cultures--I. 187 97


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