The Trypanocidal Action of Homidium, Quinapyramine and Suramin

Abstract

Homidium, quinapyramine, and suramin (Group 1I compounds) produce their trypanocidal effect in vivo only after a latent period of 24 hr. or more, during which time the trypanosomes may continue to multiply; this is in contrast to trivalent arsenical and diamidine compounds (Group I compounds), which begin to act immediately. Group 11 compounds also differ from Group I compounds in that (a) they have only a slight tendency to combine with trypanosomes, (b) they have little trypanocidal action in vitro, but (c) they make trypanosomes non-infective to fresh subinoculated mice. To explain these features it is postulated that homidium, quinapyramine, and suramin first combine in small amounts with some receptor on the trypanosome and then block some biochemical system which produces a hypothetical substance X which is needed for cell division of the trypanosome; the trypanosome is supposed to contain a preformed store of this substance X sufficient for several divisions to take place; and it is only when this store is exhausted that cell division is prevented and the trypanosome eventually dies.The purpose of this paper is to describe certain characteristics of the trypanocidal action of homidium (Ethidium; B.Vet.C. Supp. 1959, p. 27), quinapyramine (Antrycide; B.Vet.C., 1955, p. 553), and suramin, and to offer a hypothesis to explain them. These compounds differ from other trypanocidal compounds such as trivalent arsenicals and diamidines in that their trypanocidal action in vivo is manifested only after a long latent period. Experiments were undertaken to study quantitatively the behaviour of the trypanosomes during this latent period. METHODSRats or mice were infected with trypanosomes by intraperitoneal inoculation When the blood contained scanty trypanosomes, blood from the tail was diluted in a W.B.C. or R.B.C. pipette with a fluid which lysed the erythrocytes and stained the trypanosomes; the trypanosomes were then counted in a haemocytometer slide under the microscope. A suitable fluid for this purpose was: 1% methylene blue, 2 ml.; glacial acetic acid, 0.25 ml.; water, 50 ml. In the case of Trypanasoma evansi, the number of trypanosomes in a drop of blood from the tail was probably the same as that in the main volume of circulating blood. T. congolense, on the other hand, tends to accumulate in the capillaries of the tail, and the count recorded may often have been much greater than that in the circulating blood; presumably, however, the two were proportional, and this discrepancy would not affect the general argument. The animal was then treated intraperitoneally with a dose of the drug approximately double the dose which was sufficient to remove all visible trypanosomes from the blood within four days. Counts of the trypanosomes were made at suitable intervals (usually morning and evening) until no further trypanosomes were found.The trypanosomes used were T. evansi, Mathura strain, described in a previous paper (Sen, Sharma, and Hawking, 1960) which was studied in rats; and T. congolense (N.I.M.R. strai...

Effect of Repeated Administration of Berenil on Urinary Enzyme Excretion with Corresponding Tissue Pattern in Rats

“…Berenil (diminazene aceturate B. vet C) is widely used in Africa, primarily for the treatment of Trypanosoma congolense and 7: vivax infections of livestock (Williamson 1970;Holmes & Scott 1982). It has also been shown to have some values in the treatment of T gambiense and T rhodesiense infections, the human sleeping sickness, especially at the early stages of infection when the parasites are confined to the blood stream (Bailey 1968;Ogada et al 1973).…”

“…It is actively absorbed by the parasites and host cells, leading to a high concentration of drug in the cells within a short time, and it is excreted from the host system through the kidney (Hawking & Sen 1960). Some toxic effects reported for berenil include tremor, ataxia, albuminuria, nephritis and interference with carbohydrate metabolism of parasites and host (Williamson 1962(Williamson & 1970.…”

In Vitro Uptake of Isometamidium and Diminazene by Trypanosoma brucei

“…Two criteria on which Hawking and Sen (3) based their classification of trypanocides were the degree of drug uptake by the parasite under study and the effect of the drug on infectivity. They found the diamidines to be well taken up but with little effect on infectivity, whereas the inappreciably absorbed phenanthridines readily abolished infectivity.…”

In vitro effects of suramin on Trypanosoma cruzi

“…3B-D). This fact can be explained by the effect of suramin on parasite proliferation as described in other trypanosomatids [14] and is reinforced by the presence of cell debris in the host cell cytoplasm, which is indicative of amastigote degeneration and death (Fig. 3E and F).…”