THE UPTAKE OF THE TRYPANOCIDAL DRUG SURAMIN IN COMBINATION WITH LOW-DENSITY LIPOPROTEINS BY TRYPANOSOMA-BRUCEI AND ITS POSSIBLE MODE OF ACTION

In plasma, a significant part of suramin circulates in tight associati on with low-density lipoproteins (LDL). At therapeutically obtainable concentrations (100 muM) of suramin, about 85% of the total amount of the drug was bound to proteins, approximately 15% of which was bound t o LDL. The molar ratio of suramin bound to LDL in serum was 7.5. The c apacity of the high-affinity binding sites of LDL were 6.6 x 10(6) M-1 , both in Tris buffer and in ultrafiltrate of serum. Suramin (100 muM) decreased the uptake of host LDL through receptor-mediated endocytosi s by Trypanosoma brucei, with approximately 50%. LDL served as the onl y carrier for suramin uptake. Serum albumin, another important carrier for suramin in blood, was not able to promote suramin uptake, neither was delipidified plasma. The suramin taken up by T. brucei was recove red, in part, in the lysosomal fractions. It is suggested that depriva tion of the parasite from cholesterol and phospholipids by an inhibiti on of the uptake of LDL, contributes to the mode of action of suramin, in addition to the many other effects that the drug may exert on the parasite. The toxic side-effects of suramin on the host are discussed in the light of its association with circulating lipoproteins.