Disease relevance of GALACTOSAMINE

• The survival of Lewis rats with D-galactosamine-induced fulminant hepatic failure was prolonged if they were given intraperitoneal injections of single-cell suspensions of liver or bone marrow cells from normal rats [1].
• In the absence of D-galactosamine the toxicity of TNF in C3H/HeJ mice was comparable to that obtained in C3H/TifF mice, being lethal with amounts of the order of 500 micrograms [2].
• Mice deficient in IL-1beta showed unaltered sensitivity to endotoxic shock, with or without pretreatment with D-galactosamine [3].
• To study in detail the role of the liver in GABA metabolism, uptake and catabolism of GABA by isolated perfused liver from normal rats and rats with galactosamine- or carbon tetrachloride-induced liver failure were measured [4].
• The aim of the present study was to determine if brain gamma-aminobutyric acid uptake is increased in rabbits with stage II-III (precoma) hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure [5].

Psychiatry related information on GALACTOSAMINE

• By contrast, single and repeated administrations of the three above-mentioned toxins together at lower doses induced lethargy and coma with visual-evoked potential patterns similar to those observed in galactosamine-induced hepatic coma [6].
• Feeding behavior and ambulatory activity in rats with D-galactosamine-induced hepatic failure [7].
• However, only arabinose and galactosamine were significantly elevated in children with a diagnosis of conduct disorder, while only galactosamine was elevated in children with adjustment disorder [8].

High impact information on GALACTOSAMINE

• Tpl2 knockout mice produce low levels of TNF-alpha when exposed to lipopolysaccharide (LPS) and they are resistant to LPS/D-Galactosamine-induced pathology [9].
• TLR3-deficient (TLR3-/-) mice showed reduced responses to polyinosine-polycytidylic acid (poly(I:C)), resistance to the lethal effect of poly(I:C) when sensitized with d-galactosamine (d-GalN), and reduced production of inflammatory cytokines [10].
• We report here that mice homozygous for a disrupted Tnfr1 allele (Tnfr1(0)) are resistant to the lethal effect of low doses of lipopolysaccharide after sensitization with D-galactosamine, but remain sensitive to high doses of lipopolysaccharide [11].
• The calcium-dependent killing of cultured rat hepatocytes by two different membrane-active hepatotoxins, galactosamine and phalloidin, is potentiated by ethyl alcohol [12].
• Lipoprotein and lecithin: cholesterol acyltransferase changes in galactosamine-induced rat liver injury [13].

Chemical compound and disease context of GALACTOSAMINE

• A highly reproducible model of fulminant hepatic failure was developed by administering intravenously the selective hepatotoxin galactosamine hydrochloride (4.25 mmoles per kg) to genetically uniform rabbits [14].
• These findings are compatible with activation of the gamma-aminobutyric acid inhibitory neurotransmitter system contributing to cerebral neuronal inhibition in hepatic coma due to galactosamine-induced fulminant hepatic failure [15].
• CONCLUSIONS: Both TNF as well as IFN-gamma are critical mediators of liver injury in concanavalin A-treated mice, whereas hepatic DNA fragmentation and liver failure in the D-galactosamine models depend only on TNF [16].
• Finally, the results of this study do not support the hypothesis that hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure is mediated by the synergistic interaction of ammonia, mercaptans, and fatty acids on the brain [17].
• Unlike the "conventional" LTalpha-/- mice, new LTalphaDelta/Delta animals were capable of producing normal levels of systemic TNF upon lipopolysaccharide (LPS) challenge and were susceptible to LPS/D-galactosamine (D-GalN) toxicity [18].

Biological context of GALACTOSAMINE

• The same hydrazine sulfate pretreatment has now been found to protect mice against endotoxin in the D-galactosamine model with an increase in the endotoxin LD50 of approximately four orders of magnitude [19].
• The patterns of visual evoked potentials in these three syndromes were compared with those of rabbits with hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure [17].
• From these results it was concluded that the decrease of the hepatic binding protein induced by galactosamine treatment is probably responsible for the marked accumulation of serum asialoglycoproteins [20].
• Brain edema in rabbits with galactosamine-induced fulminant hepatitis. Regional differences and effects on intracranial pressure [21].
• Of note, d-galactosamine/TNF-induced hepatitis was not affected, showing that imatinib does not directly inhibit TNF-alpha-induced hepatocellular cell death [22].

Anatomical context of GALACTOSAMINE

• In addition, synovial fluid Fn contains N-acetyl galactosamine indicating the presence of O-linked oligosaccharides [23].
• Radiation-resistant spleen cells transferred D-galactosamine sensitivity, suggesting a role for macrophages [24].
• We did not exclude the possibility that lymphocytes can also transfer the response to D-galactosamine [24].
• The bacterial superantigens (SAg), toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin B (SEB), are powerful T-cell stimulators, triggering systemic release of lymphokines causing lethal shock in D-galactosamine (D-Gal)-sensitized mice [25].
• This is due to lack of UDP-D-galactose: D-N-acetyl galactosamine beta-D-galactosyl transferase from part of their red cells and probably from their leukocytes [26].

Associations of GALACTOSAMINE with other chemical compounds

• Suppression of Fas-induced activation of the caspase by IL-1beta was diminished by coadministration with D-galactosamine and reversed by coinjection with an excess amount of uridine [27].
• We studied the effects of acute and chronic ethanol feeding on hepatic regeneration in rats after partial hepatectomy and toxic liver injury produced by D-galactosamine [28].
• Glucosamine- and galactosamine-containing GAG were labeled equivalently by [3H=A1-glucose regardless of culture type, allowing incorporation into the various GAG to be compared under all conditions studied [29].
• Carbon tetrachloride and galactosamine are known to produce different patterns of acute liver injury, with maximal hepatocyte DNA synthesis at 48 hr and 5 days, respectively [30].
• In the present study, we investigated whether HGF could work as an anti-hepatitis agent for acute liver injury caused by D-galactosamine (D-GalN) using transgenic (TG) mice expressing HGF in hepatocytes, compared with wild-type (WT) mice of their siblings [31].

Gene context of GALACTOSAMINE

• In contrast, in similarly perfused liver 24 hours after treatment with D-galactosamine (800 mg/kg intraperitoneally), ET-1 caused rapid and remarkable increases in the leakage of LDH and AST from the liver accompanied by the reduction of perfusion flow to the extent similar to that observed in control livers [32].
• Using the hepatotoxin D-galactosamine (D-GalNH2), we demonstrate that MRL-lpr/lpr mice have an increased susceptibility to staphylococcal enterotoxin B (SEB)-induced lethal shock, which causes them to exhibit the septic shock-like behaviors of fur ruffling and listlessness, and death occurs within 8 to 18 h [33].
• After treating mice with lipopolysaccharide or TNFalpha in the presence of d-galactosamine, Bid was cleaved and translocated to mitochondria in hepatocytes [34].
• It is known that an acute hepatotoxicity is produced in rats by intraperitoneal administration of galactosamine; a consequence of this treatment is a marked deficiency of lecithin:cholesterol acyltransferase (LCAT) activity in the plasma compartment [35].
• Our results also show that, in contrast to expectations, IL4-/- mice are more susceptible to SEB plus low-dose D-galactosamine-induced shock and that this response is TNF-alpha-dependent [36].

Analytical, diagnostic and therapeutic context of GALACTOSAMINE

• Although hydrazine sulfate protection distinguishes between sensitivity brought on, individually, by D-galactosamine and by hypophysectomy, mice sensitized by both hypophysectomy and D-galactosamine are not protected against endotoxin lethality by hydrazine sulfate [19].
• The blood-to-brain transfer of [14C]alpha-aminoisobutyric acid was investigated by quantitative autoradiography in normal rabbits and rabbits with acute liver failure induced by the selective hepatotoxin galactosamine [37].
• Endothelin 1 aggravates acute liver injury in perfused livers of rats after treatment with D-galactosamine [32].
• The blood concentrations of endotoxin were significantly higher after intravenous injection of endotoxin in the D-galactosamine-induced liver failure group (p < 0.05) and decreased much more slowly (p < 0.05) [38].
• The models of experimental liver dysfunction included bile duct ligation (with sham-operated controls), alpha-naphthylisothiocyanate-induced intrahepatic cholestasis and galactosamine-induced diffuse hepatocellular necrosis [39].

References