Riboflavin Deficiency and Glutathione Metabolism in Rats: Possible Mechanisms Underlying Altered Responses to Hemolytic Stimuli

Riboflavin deficiency suppresses parasitic growth in malaria. Three possible mechanisms have been proposed previously to explain the survival advantage of riboflavin-deficient hosts: a) enhanced fragility of red blood cells (RBC), b) decreased formation of reticulocytes and/ or c) decreased concentrations of reduced glutathione (GSH) and ATP. The validity of these proposed mechanisms was tested by investigating whether riboflavin deficiency alters the hemolytic response to three stimuli: hydrogen peroxide (H2O2), a hypotonie medium or ferriprotoporphyrin IX(FP). Reticulocyte counts and concentrations of ATP and GSH were also determined. The percentage of hemolysis in duced by H2O2 or FP was significantly less in riboflavindeficient than in control animals. By contrast, hemolytic response to a hypotonie medium was enhanced during riboflavin deficiency. Despite diminished activity of gluta thione reducA-aseand normal glutathione peroxidase activ ity during riboflavin deficiency, the erythrocyte concentra tion of GSH was increased over that in control animals. Concentrations of ATP and hemoglobin in erythrocytes as well as the reticulocyte count were unaltered during ribo flavin deficiency. Thus, diminished malarial parasitemia in riboflavin-deficient animals occurs despite greater resist ance of RBC to either H2O2or FP-induced hemolysis, and in the presence of a normal reticulocyte count and eryth rocytes ATP concentration. Results of this study raise the possibility that Plasmodium parasites have greater require ments for flavin coenzymes, GSH or ATP than those of host erythrocytes, which may explain the apparent protec tion of the riboflavin-deficient host from malaria. J. Nutr. 118: 1149-1157, 1988.