Injection Of GalN Research Articles

D-Galactosamine hepatotoxicity : V. Role of free fatty acids in the pathogenesis of fatty liver

The role of free fatty acids (FFA) in the pathogenesis of fatty liver was investigated in female rats who received a single ip injection of d-galactosamine-HCl, (GalN), 750 mg/kg body weight. Groups of rats were either fasted for 14 hr prior to GalN injection and then fasted for the duration of the experiment or were fed ad libitum prior to and after GalN administration. Plasma FFA were determined in groups of fasting or fed rats sacrificed at intervals between 0 and 24 hr after GalN administration. The results revealed a progressive increase in plasma FFA in GalN-injected fasted rats (0 hr, 0.40 μmol/ml; 24 hr, 1.09 μmol/ml) whereas in fed animals only a modest increase in plasma FFA concentrations occurred. Hepatic triglyceride content was determined in groups of fasted and fed rats at 6 and 24 hr after GalN administration. Hepatic triglycerides, in fasted rats, were increased 7-fold at 6 hr (22.4 ± 8.5 mg/g) and were markedly increased at 24 hr (114.8 ± 18.4 mg/g). In contrast, feeding protected the rats from the development of fatty liver since hepatic triglycerides were only twice controls at 6 hr and 4-fold increased 24 hr after GalN. Ultrastructural studies were performed at 15, 24, and 48 hr after GalN in fed and fasted rats. Electron microscopy disclosed hepatocellular necrosis and profound fat accumulation in the fasted animals; however, feeding afforded marked protection against the development of fatty liver and hepatic injury. The results of these studies indicate that the GalN-induced fatty liver is associated with a sustained elevation of plasma FFA. The increase in plasma FFA can be prevented by feeding the animals prior to and after GalN administration suggesting that a stimulus for FFA elevation may be the alterations in carbohydrate metabolism known to be induced by GalN in rat liver.

Lipoprotein Abnormalities in Galactosamine Hepatitis: A Model of Experimental Lecithin:Cholesterol Acyltransferase Deficiency

D-galactosamine (GalN) produces, in the rat, an acute hepatitis, LCAT deficiency, and plasma lipoprotein abnormalities similar to those of human liver disease. Rats were sacrificed at intervals up to 24 h after a single ip injection of GalN, 750 mg/kg. No alpha band was found by plasma lipoprotein electrophoresis 12-24 h after GalN. Plasma LCAT activity was decreased 45% at 6 h and was < 10% of normal at 24 h. Cholesteryl esters decreased to 36% of total cholesterol at 12 h (control 70%) and at 24 h after GalN were only 15% of total cholesterol. Fractionation of plasma phospholipids at 24 h revealed lecithin increased to 68% of total phospholipid (control 46%), and lysolecithin decreased to 12% (control 25%). The increase of the lecithin/lysolecithin ratio to 5.6 after GalN (control 1.8) may reflect decreased LCAT activity. Arachidonyl esters accounted for only 9% of cholesteryl esters after GalN compared to 64% in controls. Lipoproteins were isolated by sequential ultracentrifugation: VLDL (d < 1.006); L...

D-Galactosamine hepatotoxicity : IV. Further Studies of the Pathogenesis of Fatty Liver

Female rats received a single ip injection of d-galactosamine-HCl, (GalN), 750 mg/kg body weight. Groups of animals were sacrificed at intervals until 72 hr after injection and their plasma lipids, lipoproteins, and hepatic triglyceride content determined. The results revealed a progressive increase in hepatic triglycerides, which was apparent within 2 hr of GalN injection, reaching a maximum of 114.8 ± 18.4 mg/g wet wt liver at 24 hr followed by a gradual return toward normal values. Despite the accumulation of fat in the liver, the plasma triglycerides remained normal or were slightly elevated. Striking changes were observed in the plasma lipoprotein pattern on agarose electrophoresis. These changes, observed within 2 hr of injection, were a decrease and then absence of the α- and pre-β-lipoprotein bands and the appearance of an abnormally migrating β-band. Characterization of the plasma lipoproteins by zonal ultracentrifugation resulted in the isolation of a triglyceride-rich lipoprotein of abnormal density. By light microscopy the hepatocytes were enlarged due to massive fatty droplet accumulation. Ultrastructural studies revealed distention of the Golgi zones with lipoprotein droplets and secretion of these lipid droplets into the perisinusoidal space. Studies with Triton WR 1339 disclosed that plasma triglycerides were higher post-Triton in the GalN-treated rats than in the controls. The results of all of these studies indicate that GalN produces a fatty liver although hepatic lipoprotein secretion is not inhibited.

The development of cholangiofibrosis and hepatomas in galactosamine induced cirrhotic rat livers.

Daily injection of GalN leads to the development of cholangiofibrosis and hepatomas in rat liver. This development depends on the metabolization of GalN to GalN-1-P, UDP-hexosamines, N-acetyl-hexosamine-P, and UDP-N-acetyl-hexosamines.