Xylitol was investigated for its ability to ameliorate
hemolytic anemia induced by
acetylphenylhydrazine in rabbits. Animal experiments were performed using two different concentrations of
xylitol, a 5% and
a 10%
solution with a total dose of 2 g/kg
body weight and infusion rates of 10 mg and 20 mg
xylitol per kg
body weight per minute respectively. Two doses of
acetylphenylhydrazine (APH), 5 and 10 mg per kg, were injected intraperitoneally as hemolytic inducers in different groups of rabbits. All the rabbits infused with
xylitol showed significantly less acute APH-induced
hemolysis. The isotonic 5%
xylitol solution was found to maintain and restore the hematological parameters (packed cell volume,
hemoglobin concentration,
reduced glutathione (GSH) content, and reticulocyte counts) better than the 10%
xylitol solution. Increased 51CR-red cell survival confirmed the beneficial effect of
xylitol. The survival of erythrocytes as represented by
chromium-labeling in rabbits infused with 5%
xylitol after treatment with 10 mg/kg APH increased from about 33% (the survival of red cells in rabbits injected with APH alone) to 67% of normal rabbits' red cell survival. Erythrocytes in APH-treated animals took up
xylitol more readily than erythrocytes from control animals. Our results in rabbits suggest that (1) non-toxic dosage of
xylitol is effective in ameliorating the hemolytic episode induced by
APH, (2) there is a dose relationship between the hemolytic effect induced by APH and the preventive effect offered by
xylitol, (3)
drug-challenged cells effectively acquired two to three fold more
xylitol to compensate for the cellular needs than that of the normal cells, and (4) sufficient
xylitol (55 mg/dl) to act as substrate for
xylitol dehydrogenase was recovered intracellularly in
drug-challenged rabbit erythrocyte in vivo, in spite of a low plasma (less than 30 mg/dl) concentration of the substrate. This antihemolytic affect of
xylitol is likely accomplished through
NADPH generation, which maintains the level of GSH and protects the
hemoglobin and other structural and functional
proteins against peroxidative damage.