title: The uptake of the trypanocidal drug suramin in combination with low-density lipoproteins by Trypanosoma brucei and its possible mode of action.
abstract: In plasma, a significant part of suramin circulates in tight association with low-density lipoproteins (LDL). At therapeutically obtainable concentrations (100 microM) of suramin, about 85% of the total amount of the drug was bound to proteins, approximately 15% of which was bound to LDL. The molar ratio of suramin bound to LDL in serum was 7.5. The capacity 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 microM) decreased the uptake of host LDL through receptor-mediated endocytosis by Trypanosoma brucei, with approximately 50%. LDL served as the only 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 recovered, in part, in the lysosomal fractions. It is suggested that deprivation of the parasite from cholesterol and phospholipids by an inhibition 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.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Utrecht University, The Netherlands.
authors.forename: E L
authors.initials: EL
authors.lastname: Vansterkenburg
authors.forename: I
authors.initials: I
authors.lastname: Coppens
authors.forename: J
authors.initials: J
authors.lastname: Wilting
authors.forename: O J
authors.initials: OJ
authors.lastname: Bos
authors.forename: M J
authors.initials: MJ
authors.lastname: Fischer
authors.forename: L H
authors.initials: LH
authors.lastname: Janssen
authors.forename: F R
authors.initials: FR
authors.lastname: Opperdoes
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D004359:Drug Therapy, Combination; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D011485:Protein Binding; D013498:Suramin / Q000378:metabolism* / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; D008077:Lipoproteins, LDL; D013498:Suramin