Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In previous studies of rats with portacaval shunts, elevated gamma-globulin levels 2 weeks after shunt were attributed to antibodies to bacterial lipopolysaccharide, which were normally filtered by the liver. This study was designed to determine the tempo of this rise and the magnitude of hepatocellular damage within the first 4 days of the operation. Acute reversible hepatocellular damage was shown by elevated levels of aspartate aminotransferase which returned to normal within 48 hours. This was confirmed on histology. There was no rise in gamma-globulin during this study but levels of albumin were better maintained in shunted rats than in sham-operated rats. Levels of alpha2 and beta-globulin in the former fell in comparison with the latter animals.
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PMID:Acute biochemical and histological effects of portacaval shunt in the normal rat. 5 Jun 26

Mice infected with Schistosoma mansoni were highly sensitive to the lethal effects of bacterial lipopolysaccharide (LPS). The hyper-reactive state of LPS coincided with the development around the parasite eggs of multiple granulomas in the liver. Elevated aspartate transaminase levels in blood and severe hypoglycaemia in LPS-challenged animals indicated extensive liver parenchymal cell damage. There was also a complete depletion of glycogen in hepatocytes of these animals. From this work and studies on other hepatitis models, it is suggested that individuals affected with granulomatous disorders may be at risk because of everyday exposure to LPS from the gut.
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PMID:Increased hepatotoxicity of bacterial lipopolysaccharide in mice infected with Schistosoma mansoni. 55 82

Neutrophil (PMN) infiltration is an early occurrence in the liver after exposure to hepatotoxic doses of endotoxin lipopolysaccharide (LPS). The purpose of this study was to test the hypothesis that PMNs contribute to the pathogenesis of LPS hepatotoxicity. The immunoglobulin fraction from serum of rabbits immunized with rat PMNs (anti-PMN Ig) was administered intravenously to rats 18 and 6 hours before exposure to an hepatotoxic dose of LPS (Escherichia coli 0128:B12). This protocol caused a greater than 95% reduction in circulating PMNs, which was maintained for the duration of the study. The immunoglobulin fraction from nonimmunized rabbits was used as a control (control Ig). Rats pretreated with control Ig exhibited a marked increase in the number of PMNs in the liver 1.5 hours after LPS exposure. This increase in hepatic PMNs was significantly reduced by pretreatment with anti-PMN Ig. Marked elevations in both alanine and aspartate aminotransferase activities (1086 +/- 311 and 880 +/- 183 SF units/ml, respectively) were observed in plasma from control Ig-treated rats 6 hours after intravenous administration of LPS (3.0 mg/kg). The response to LPS was greatly attenuated in animals receiving anti-PMN Ig (145 +/- 111 and 224 +/- 49 SF units/ml alanine and aspartate aminotransferase activities, respectively). Pretreatment of rats with immunoglobulins to rat lymphocytes reduced numbers of circulating lymphocytes but did not afford protection against the hepatotoxic effects of LPS. These results suggest that PMNs contribute to the pathogenesis of LPS hepatotoxicity.
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PMID:Neutrophil depletion protects against liver injury from bacterial endotoxin. 153 88

Lead markedly augments the lethality of endotoxin lipopolysaccharide (LPS) in rats. In this model of LPS toxicity, the liver is severely injured. Much of the tissue injury produced by LPS is thought to be mediated by the cytokine tumor necrosis factor (TNF). Tumor necrosis factor recently has been speculated to be a mediator of several models of liver injury such as that produced by galactosamine. To investigate the possible role of TNF in the lead-enhanced LPS toxicity model, we administered doses of lead acetate (15 mg/kg), LPS (100 micrograms/kg), or TNF (6.25 x 10(6) U/kg) that produced minimal changes in liver enzymes. However, when lead was administered simultaneously with either LPS or TNF, serum aspartate transaminase, alanine transaminase, alkaline phosphatase, glutamyl transpeptidase, and plasma triglyceride levels were markedly increased. Lead + LPS treatment increased both peak serum TNF concentrations and TNF "area under the curve" as compared with LPS alone. We conclude that lead not only enhances LPS lethality but also LPS liver injury. Furthermore, lead enhances TNF liver injury and increases LPS-stimulated serum TNF levels. These data suggest that the lead-enhanced LPS model offers a system for studying TNF-induced liver injury.
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PMID:Lead enhances lipopolysaccharide and tumor necrosis factor liver injury. 167 39

Intravenous injection of lipopolysaccharide and D-galactosamine, at doses of 0.2 micrograms/kg and 800 mg/kg, respectively, elicited massive hepatic necrosis within 24 hr in C3H/HeN mice. The plasma L-alanine aminotransferase (ALT, E.C. 2.6.1.2) or L-aspartate aminotransferase (AST, E.C. 2.6.1.1) activities at this point reached more than 2,000 IU/L. However, overt hepatic injury as evaluated by the plasma aminotransferase activities did not develop in mice in which only lipopolysaccharide or only D-galactosamine was injected. No tumor necrosis factor-like activities could be detected in the plasma of galactosamine- and lipopolysaccharide-injected mice as determined by the assay of cytotoxicity to highly tumor necrosis factor-sensitive L-P3 cells through the experimental period of 24 hr. However, passive immunization against mouse tumor necrosis factor-alpha with polyvalent rabbit anti-mouse tumor necrosis factor-alpha antiserum, which was able to neutralize the cytotoxic effects of recombinant mouse tumor necrosis factor-alpha on L-P3 cells, could protect the mice from the development of hepatic injury in a dose-dependent manner. Simultaneous injection of recombinant human tumor necrosis factor-alpha, instead of lipopolysaccharide, with 800 mg/kg of D-galactosamine in lipopolysaccharide-resistant C3H/HeJ mice sensitized the animals more than one thousand-fold to the development of hepatic injury. The livers appeared to be morphologically similar to those of galactosamine- and lipopolysaccharide-injected C3H/HeN mice.
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PMID:Involvement of tumor necrosis factor-alpha in development of hepatic injury in galactosamine-sensitized mice. 222 17

Acute hepatic necrosis was induced by a single i.v. injection of lipopolysaccharide (LPS) into C57BL/6 mice following immunization with syngeneic liver protein and adjuvant. Sixty percent of the mice died of massive hepatocyte necrosis within 48 hours of LPS injection. The serum lactate dehydrogenase and aspartate aminotransferase levels were markedly elevated. The fatal and hepatotoxic action of LPS was prevented by pretreatment with FUT-175 (1.6 mg/kg), a synthetic protease-inhibitor. The inhibitory effects of FUT-175 was not demonstrated when the agent was given to the mice 2 h after the administration of LPS. These results seem to indicate that the hepatotoxic effects of LPS are mediated by endogenous host mechanisms in which proteases play an important role.
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PMID:[Effects of FUT-175 on mouse model of acute hepatic necrosis induced by endotoxin following immunological procedure]. 238 83

Activated macrophages convert L-arginine to citrulline and unstable nitrogen oxides that have cytotoxic properties. We recently have shown that the inhibition of protein synthesis in Kupffer cell (KC):hepatocyte (HC) coculture, following exposure to gram-negative bacterial endotoxin (lipopolysaccharide), is due to the metabolism of L-arginine by this cytotoxic pathway. Although this finding supports a role for activated KCs and the L-arginine-dependent mechanism in the HC dysfunction seen in sepsis, it and previous studies have failed to demonstrate direct damage to HCs by adjacent KCs. The current study was undertaken to determine if KCs exposed to lipopolysaccharide could directly damage HCs and, if so, whether the damage was dependent on the metabolism of L-arginine. By using the release of aspartate aminotransferase as a marker of HC damage, it was found that a significant aspartate aminotransferase release by KC:HC cocultures in response to lipopolysaccharide occurred only if L-arginine was present. In addition, requirements for significant aspartate aminotransferase release included KC:HC ratios of 7.5:1 or greater and L-arginine concentrations of 1 mmol or more. Although the KC-induced damage was mild, these results show that in vitro HC damage in KC:HC coculture does require the metabolism of L-arginine and supports a hypothesis that toxic L-arginine metabolites may contribute to liver cell damage in patients with sepsis.
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PMID:Kupffer cell cytotoxicity to hepatocytes in coculture requires L-arginine. 258 66

Reversible endotoxic shock was induced in adult rats by i.v. injection of Escherichia coli O111:B4 lipopolysaccharide (1.6 mg/100 g). The shock progression was evaluated by measuring serum glucose levels as well as activities of aspartate aminotransferase (GOT) and alkaline phosphatase in serum. A rapid increase of serum glucose levels occurs, after LPS injection, followed by hypoglycaemia (minimum values at 6 h) with progressive reversion to control values. Serum GOT activity increased (twofold) 6 h after endotoxin administration and returned to control values at 72 h. No appreciable changes occurred in serum alkaline phosphatase activity. Endotoxaemia produced a decrease in the cytochrome P-450 levels in all target organs considered: lung, adrenal glands and liver. The progressive decrease in the serum albumin concentration as well as changes of the physical properties of the plasma membranes observed in vivo, can not be explained only by direct interaction of endotoxin with the target organs, underlining the importance of serum mediators in the induction of the shock response.
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PMID:Induction of reversible shock by Escherichia coli lipopolysaccharide in rats. Changes in serum and cell membrane parameters. 306

The biphasic behaviour observed in endotoxin-induced shock attributed to a direct interaction of bacterial lipopolysaccharides with the cell membrane and an indirect activation of multiple homeostatic regulatory mechanisms, cannot be completely elucidated with in vivo studies. In primary cultures of adult rat hepatocytes, lipopolysaccharide from Escherichia coli 0111:B4 affects the cytochrome P450 levels directly; however, albumin and aspartate aminotransferase secretion are induced by some mediators present in the sera of animals in acute-phase shock.
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PMID:Direct and mediated Escherichia coli lipopolysaccharide action in primary hepatocyte cultures. 329 5

Rats and mice infected with Trypanosoma lewisi and Trypanosoma musculi, respectively, showed hyperreactivity to lipopolysaccharide (LPS) from gram-negative bacteria. Fatal shock could be precipitated with a dose of LPS 100 to 1,000 times less in infected compared with noninfected animals. In trypanosome-infected rats and mice, extensive liver damage was evident after LPS challenge. These animals showed a pronounced hypoglycemia, marked elevation of blood aspartate transaminase level, and diffuse severe degeneration and total depletion of glycogen in hepatocytes. Only minor changes were observed in noninfected animals given the same dose of LPS. No mononuclear phagocytic cell infiltration was observed in the liver of infected animals. The most striking change was the great increase in size and the probable increase in phagocytic activity and number of sinusoidal Kupffer cells. We suggest that elevated Kupffer cell activity in trypanosome-infected animals may play a role in LPS-induced hepatotoxicity.
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PMID:Lipopolysaccharide hyperreactivity of animals infected with Trypanosoma lewisi or Trypanosoma musculi. 650 Jul


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