piperidines and Methemoglobinemia

Heinz body anemia was induced in dogs by consecutive oral administration of 200 mg/kg and 60 mg/kg of aminopyrine, 200 mg/kg of phenacetin and 5 mg/kg of acetylphenylhydrazine, for either 8 or 16 weeks. Biochemical analysis showed a decrease of haptoglobin in plasma and reduced-glutathion in red blood cells in association with anemia. Hematologically, an increase in osmotic fragility and cell volume of erythrocytes were also noted. Pathological examination revealed marked erythrophagia and hemosiderosis in the reticuloendothelial system of treated animals. A new anti-inflammatory analgesic 31252-S (3-(1-hydroxy-2-piperidinoethyl)-5-phenylisoxazole citrate) was also tested for the hemolytic effects in dogs. Blood analyses revealed a slight increase of Heinz bodies and a decrease of reduced-glutathion in red blood cells without anemia. These findings suggest that 31252-S have weaker oxidant properties than those of aminopyrine and phenacetin. The present studies showed that the concentration of reduced-glutathion in red blood cells of non-treated dogs was approximately 50% lower than that of the erythrocytes of normal human beings. This finding appeared to correspond with high susceptibility of red blood cells to hemolytic effects of oxidant-drugs in dogs.

Topics: Aminopyrine; Anemia, Hemolytic; Animals; Bilirubin; Blood Cell Count; Blood Proteins; Dogs; Female; Glucosephosphate Dehydrogenase; Glutathione; Isoxazoles; Liver; Male; Methemoglobinemia; Osmotic Fragility; Oxazoles; Phenacetin; Phenylhydrazines; Piperidines; Spleen