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 hypotonic medium or
ferriprotoporphyrin IX (FP). Reticulocyte counts and concentrations of
ATP and GSH were also determined. The percentage of
hemolysis induced by H2O2 or FP was significantly less in
riboflavin-deficient than in control animals. By contrast, hemolytic response to a hypotonic medium was enhanced during
riboflavin deficiency. Despite diminished activity of
glutathione reductase and normal
glutathione peroxidase activity during
riboflavin deficiency, the erythrocyte concentration 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
riboflavin deficiency. Thus, diminished malarial
parasitemia in
riboflavin-deficient animals occurs despite greater resistance of RBC to either H2O2- or FP-induced
hemolysis, and in the presence of a normal reticulocyte count and erythrocytes
ATP concentration. Results of this study raise the possibility that Plasmodium parasites have greater requirements for
flavin coenzymes, GSH or
ATP than those of host erythrocytes, which may explain the apparent protection of the
riboflavin-deficient host from
malaria.