Experimental hepatitis induced by d-galactosamine

Keppler, Dietrich; Lesch, R; Reutter, Werner; Decker, Karl

doi:10.1016/0014-4800(68)90042-7

Cited by 489 publications

(237 citation statements)

References 12 publications

Supporting

Mentioning

220

Contrasting

Unclassified

Order By: Relevance

“…Inasmuch as mice treated with SEBϩD-galN rarely survived longer than 10 hours, histopathologic analyses were performed at 9 hours in the D-galN-sensitized mice. Compared with the normal liver sections from naïve mice, liver sections from mice that received D-galN alone exhibited mild hepatitis with focal areas of infiltration with mononuclear cells, as had been demonstrated in previous studies 34,35 (Figure 5). Mice that received SEB alone also demonstrated perivascular infiltration with mononuclear cells.…”

Section: Distinct Histopathologic Profiles Between Tss With and Withosupporting

confidence: 76%

“…This results in profound reduction in the ability of cells to produce uridine triphosphate, thereby affecting RNA and protein synthesis. 33,34,36 Although D-galN by itself can cause hepatocyte apoptosis and necrosis, 33,34 hepatocytes are also rendered extremely susceptible to the cytotoxic actions of cytokines such as TNF-␣ by D-galN. SAgs induce TNF-␣ production in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…32 D-galN, the commonly used sensitizing agent for inducing TSS, is extremely toxic even when administered alone, 33 and induces liver injury mimicking viral hepatitis. 34,35 D-galN and actinomycin profoundly sensitize hepatocytes to tumor necrosis factor-␣ (TNF-␣)-mediated injury. 36 Therefore, murine TSS is characterized by massive liver failure alone, with dramatically elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations, whereas TSS in humans is characterized by MODS.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Human Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome

Tilahun

Marietta

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Among the exotoxins produced by Staphylococcus aureus and Streptococcus pyogenes, the superantigens (SAgs) are the most potent T-cell activators known to date. SAgs are implicated in several serious diseases including toxic shock syndrome (TSS), Kawasaki disease, and sepsis. However, the immunopathogenesis of TSS and other diseases involving SAgs are still not completely understood. The commonly used conventional laboratory mouse strains do not respond robustly to SAgs in vivo. Therefore, they must be artificially rendered susceptible to TSS by using sensitizing agents such as D-galactosamine (D-galN), which skews the disease exclusively to the liver and, hence, is not representative of the disease in humans. SAg-induced TSS was characterized using transgenic mice expressing HLA class II molecules that are extremely susceptible to TSS without D-galN. HLA-DR3 transgenic mice recapitulated TSS in humans with extensive multiple-organ inflammation affecting the lung, liver, kidneys, heart, and small intestines. Heavy infiltration with T lymphocytes (both CD4 ؉ and CD8؉), neutrophils, and macrophages was noted. In particular, the pathologic changes in the small intestines were extensive and accompanied by significantly altered absorptive functions of the enterocytes. In contrast to massive liver failure alone in the D-galN sensitization model of TSS, findings of the present study suggest that gut dysfunction might be a key pathogenic event that leads to high morbidity and mortality in humans with

show abstract

Section: Distinct Histopathologic Profiles Between Tss With and Withosupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Human Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome

Tilahun

Marietta

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…This review discusses two of the more widely used hepatotoxins, galactosamine [29][30][31][32][33][34][35][36] and acetaminophen. [37][38][39][40][41][42][43][44] Over the past 30 years, acetaminophen overdose has become the most common cause of FHF in the United Kingdom.…”

Section: Chemical Modelsmentioning

confidence: 99%

“…This leads to depletion of intracellular uridine moieties, which in turn disturbs hepatocyte RNA metabolism, ultimately leading to hepatocyte necrosis. 31,[45][46][47][48] Whether necrosis is caused solely by these biochemical changes or whether other factors, such as endotoxin or Kuppfer cell activation, are required is not clear. Models based on both small and large animals ( Table 2) have shown the development of FHF in a reproducible fashion when galactosamine was administered.…”

Section: Galactosamine Modelsmentioning

confidence: 99%

Animal models of fulminant hepatic failure: A critical evaluation

et al. 2000

View full text Add to dashboard Cite

Few conditions in medicine are more dramatic or more devastating than acute liver failure. Our understanding and treatment of this condition have been limited by the lack of satisfactory animal models. The most widely used models consist of surgical anhepatic and devascularization procedures and hepatotoxins, such as galactosamine and acetaminophen. Potential disadvantages with surgical models are their inability to recreate the inflammatory milieu that exists in acute liver failure and their reliance on surgical expertise. Models using hepatotoxins are free of such constraints. Galactosamine-induced hepatotoxicity is more predictable than acetaminophen, but its cost and lack of a human equivalent clinical syndrome has restricted its use. Acetaminophen-based models offer the greatest potential but have proven the most difficult to develop because of difficulties with reproducibility and refractory anemia. Although progress has been made, research must continue in this area to establish an animal model with minimal disadvantages that would accurately reflect the clinical syndrome seen in humans.

show abstract

Effect of an herbal protein, CI-1, purified fromCajanus indicus, in models of liver failure in mice

1999

View full text Add to dashboard Cite

Acute liver damage models in Swiss albino mice (male; 25–30 g) induced by paracetamol (300–500 mg/kg); β‐galactosamine (500 mg/kg); and 40% ethanol (2 ml / 100 g) were studied. Clinical indications of chronic hepatocellular necrosis were manifested within 24 h of toxic doses. Initially, serum transaminases, alkaline phosphatase, lactate dehydrogenase, bilirubin, and triglycerides were markedly increased; in addition, the plasma prothrombin time was prolonged. The total serum protein and serum albumin were significantly decreased in comparison to controls. Treatment of severely liver‐injured mice with a protein, CI‐1, purified from the leaves of Cajanus indicus at a dose of 100 μg/ml i.p. regularly for 14 days significantly lowered the respective serum enzymes such as transaminases (SGOT, SGPT), alkaline phosphatases (ALK), and lactate dehydrogenase (LDH), prevented the loss of liver protein content, and improved the altered plasma coagulability. Histological studies of liver of treated (hepatoxins) mice reveal massive centrilobular necrosis, Kupffer's cells hyperplasia, and periportal fatty changes in contrast to control animals. Treatment with CI‐1 in liver‐damaged animals showed near normal histology. CI‐1 may be a useful approach in the treatment of liver disorders. Drug Dev. Res. 48:76–83, 1999. © 1999 Wiley‐Liss, Inc.

show abstract

Experimental hepatitis induced by d-galactosamine

Cited by 489 publications

References 12 publications

Human Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome

Human Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome

Animal models of fulminant hepatic failure: A critical evaluation

Effect of an herbal protein, CI-1, purified fromCajanus indicus, in models of liver failure in mice

Contact Info

Product

Resources

About