In Vitro Studies on the Effect of Chloroquine Phosphate on the Metabolism of the Rat Red Blood Cells

Abstract

Evidence is presented to show that in vitro. (1) High levels of chloroquine phosphate can induce hemolysis in the rat red blood cells; and (2) chloroquine-induced hemolysis is characterised by a fall in GSH levels, unless glucose is present in very high concentrations* Chloroquine phosphate is a member of the 4-aminoquinoline series of drugs used for treating acute malaria due to infection fctj Plasmodium vivdx« Plasmodium falciparum. Plasmodium malariae and Plasmodium ovale. In vitro studies were made on red blood cells incubated with chloroquine phosphate to investigate a possible chloroquine-induced hemolysis in rat red blood cells. A wide range of chloroquine phosphate concentrations were tested. After 4 hours incubation of the mixture at 3?°C; 6,3 1 10~% caused only - 2. hemolysis in the rat red blood cells; whereas 2.5 x 10 !-i chloroquine caused 66,5a hemolysis. Complete hemolysis was however observed when 4.2 x 10 chloroquine phosphate was used in the incubation system. -1 -2 Either 3.78 x 10 M glucose or 2,0 x 10 M ATP protected the red _2 blood cells from hemolysis induced by 2.5 x 10 M chloroquine phosphate. Hemolysis induced by chloroquine phosphate was found to be characterised by (a) a fall in GSH level, and (b) an increase in the osmotic fragility of the rat red blood cells. These characteristics are similar to primaquine- induced hemolysis in -.red blood cells. The possibility is discussed that based upon osmotic fragility studies, the site of hemolytic action of chloroquine phosphate could be directly on the red cell membrane where the drug might interfere with sulfhydryl groups.