Trypanosoma cruzi: differentiation to metacyclic trypomastigotes in the presence of ADP-ribosyltransferase inhibitors.
The participation of ADP-ribosyltransferase in Trypanosoma cruzi differentiation to the metacyclic stage was evaluated by analyzing morphogenesis blockage by specific enzyme inhibitors: benzamide, 3-aminobenzamide, theophylline, and nicotinamide. In vitro assays showed a statistically significant reduction in the number of metacyclic forms only when any one of the four inhibitors was added during the period of interaction between epimastigote and Triatoma infestans intestinal homogenate or when present throughout the subsequent culture period in Grace's medium. When nicotinamide or benzamide was present during both interaction and culture period, morphogenesis was virtually abolished (less than or equal to 2%). In the in vivo assays, mice inoculated with parasites obtained from the insect vectors fed with trypomastigote-infected blood containing one of the four enzyme inhibitors developed lower parasitemias and showed longer survival in every case, compared with the respective controls. These findings suggest ADP-ribosyltransferase participation in T. cruzi differentiation both in vitro and in vivo.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D014355:Chagas Disease / Q000188:drug therapy; D051379:Mice / Q000469:parasitology; D009536:Niacinamide / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D013806:Theophylline / Q000494:pharmacology; D014224:Triatoma / Q000469:parasitology; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009536:Niacinamide; C037689:benzamide; C025160:3-aminobenzamide; D013806:Theophylline