Effects of Methylglyoxal bis(Guanylhydrazone) on Trypanosomatid Flagellates: Inhibition of Growth and Nucleoside Incorporation in Trypanosoma brucei*

Publisher Website
Google Scholar
Abstract
Methylglyoxal bis(guanylhydrazone) (MGBG) at 0.5 mM, had little effect in vitro on Blastocrithidia culicis, Crithidia oncopelti and Leishmania spp., but completely inhibited growth of T. brucei. Inhibition became irreversible after a 3 h exposure of T. brucei culture procyclics. Treated organisms remained motile, but failed to divide. Polyamines, spermidine and spermine did not reverse the anti-trypanosome action of MGBG (preloading of cells or concurrent administration). Two i.p. injections of the drug at a concentration of 50 mg/kg body weight at a 1 day interval greatly reduced the parasitemia of T. brucei and T. congolense in rats. Trypanosome infections, however, relapsed and killed the animals in 6 days after treatment. It was evident from the results of tracer experiments with T. brucei that MGBG significantly lowered incorporation of [3H]thymidine by culture procyclics and of [3H]uridine by bloodstream forms; in both stages [3H]leucine incorporation was only slightly inhibited. MGBG probably interferes with nucleoside incorporation by Trypanosoma and its mode of action is probably different in bloodstream and culture procyclics.

This publication has 11 references indexed in Scilit: