Ferriprotoporphyrin IX binding substances and the mode of action of chloroquine against malaria.

Bovine serum albumin and preparations of cell sap from malaria parasites and normal erythrocytes were tested for ability to protect cellular membranes against the toxicity of ferriprotoporphyrin IX (FP) and a chloroquine-FP complex. Suspensions of Plasmodium berghei (approximately 7 X 10(6) parasites per ml, isolated from saponin-lysed, infected erythrocytes) were used as a test system. Toxicity was monitored by measuring changes in turbidity of these suspensions at 700 nm. Parasite cell sap (0.56 mg protein per ml) and albumin (1 mg per ml) completely prevented the toxicity of 40 micrometers FP. Erythrocyte cell sap (8.6 mg of hemoglobin per ml). Provided only partial protection from 40 micrometers FP. Neither the cell sap preparations nor albumin eliminated the toxicity of a chloroquine-FP complex formed from 20 micrometers chloroquine and 40 micrometers FP. These observations suggest that the cell sap preparations contain FP binding substances and that the mode of action of chloroquine may be to shunt FP away from a nontoxic complex with these substances and into a toxic chloroquine-FP complex.