2-Deoxy-D-galactose, in a dose of 3 mmol/kg, was administered intraperitoneally twice daily to young rats for periods up to 12 weeks. This dosage schedule resulted in recurrent
phosphate trapping predominantly in liver.
UTP deficiency was excluded by simultaneous
uridine injections.
Phosphate trapping was caused by the rapid accumulation of
2-deoxy-D-galactose 1-phosphate and was most pronounced in liver but also demonstrated in small intestine, brain, spleen, and thymus. The marked, although transient, drop in the hepatic content of
inorganic phosphate triggered the catabolism of
adenine nucleotides and a loss of
ATP. Other metabolic pathways affected by
phosphate deficiency include glycogenolysis and glycolysis. Increasing with time, repeated doses of the
galactose analog led to retardation and arrest of growth,
hepatomegaly, and
splenomegaly. The average relative liver and spleen weights were elevated 2.5- and 4.5-fold, respectively, after 12 weeks of treatment. Liver damage was indicated by hyperbilirubinaemia and a progressive rise in the activity in plasma of
sorbitol dehydrogenase,
alkaline phosphatase, and
gamma-glutamyltransferase. Examination by light and electron microscopy showed increasing numbers of vacuoles, surrounded by a single membrane, in hepatocytes, sinusoidal endothelial cells, and Kupffer cells. Focal cytoplasmic degeneration in hepatocytes was occasionally indicated by formation of autophagic vacuoles and finger print lysosomes. Hepatocytes of 2-deoxy-D-galactose-treated rats showed a dissociation and fragmentation of the rough endoplasmic reticulum. Sinusoidal endothelial cells and Kupffer cells were markedly enlarged, the latter contained a PAS-positive but
amylase resistant substance. Extrahepatic changes included an increased occurrence of vacuolated cells in thymus.
Phosphate trapping and its metabolic consequences are common phenomena in the experimental injury induced b
2-deoxy-D-galactose and in some
hereditary diseases such as uridylyltransferase deficiency galactosaemia,
fructose intolerance and
glucose-6-phosphatase deficiency.