A rapid method for testing in vivo the susceptibility of different strains of Trypanosoma cruzi to active chemotherapeutic agents

Abstract

A method is described which permits to determine in vivo and in a short period of time (4-6 hours) the sensitivity of T. cruzi strains to known active chemotherapeutic agents. By using resistant- and sensitive T. cruzi strains a fairly good correlation was observed between the results obtained with this rapid method (which detects activity against the circulating blood forms) and those obtained with long-term schedules which involve drug administration for at least 20 consecutive days and a prolonged period of assessment. This method may be used to characterize susceptibility to active drugs used clinically, provide information on the specific action against circulating trypomastigotes and screen active compounds.

In vitro and in vivo experimental models for drug screening and development for Chagas disease

“…Due to the broad spectrum of bioactivity of various drugs in different stocks of T. cruzi (Brener & Chiari 1967, Brener et al 1976, Andrade et al 1977, Filardi & Brener 1984, Camandaroba et al 2003, it is important to analyse the activity of new compounds against parasites of different lineages, including strains resistant to Bz and nifurtimox (Andrade et al 1985, Filardi & Brener 1987. However, one of the main limitations of such an analysis is the difficulty of using different subpopulations of T. cruzi, including the Y and Colombian strains transfected with β-galactosidase, other enzymes or green fluorescent protein.…”

Biological characterization of Trypanosoma cruzi strains

“…The resistance of T. cruzi to chemotherapeutic drugs varies from 0% to 100% (Filardi & Brener 1984) and it has been related to miotropic preferences of strains and predominance of broad blood forms, while sensitive strains are miotropic or reticulotropic, showing predominance of slender forms (Melo & Brener 1978, Andrade et al 1985, Neal & Van Bueren 1988. Some aspects as variations in absorption and metabolism of drug, incorporation to different infected tissues, synergic intervention of immune system as well as clinic phase of infection or morphological stage can be implicated (De Castro & De Meirelles 1987, Toledo et al 1990).…”

In vitro and in vivo trypanocidal activity of the ethyl esters of N-allyl and N-propyl oxamates using different Trypanosoma cruzi strains

“…Comparative trypanocidal effect of Benznidazole, Nifurtimox, the ethyl ester of N-propyl oxamate and the ethyl ester of N-allyl oxamate on cultured epimastigotes and on parasitaemia using different T. cruzi strains At the peak of maximum parasitaemia, a single dose of the drug (500 mg/kg) was given by the oral route and the parasitaemia was determined before and 2, 4 and 6 h after the treatment, according to Filardi and Brener [14]. T.cruzi strains Figure 4.…”

“…Control (without Bz or Nx). At the peak of maximum parasitaemia, a single dose of the drug (500 mg/kg) was given by the oral route and the parasitaemia was determined before and 2,4 and 6 h after treatment, according to Filardi and Brener [14]. Compostela and Miguz strains were resistant to the treatment with Nx and Bz.…”

“…To test the trypanocidal activity of drugs (Bz, Nx, NPOx, NAOx, Et-NPOx and EtNAOx), at the peak of maximum parasitaemia, a single dose of 500 mg/kg of a drug was given by the oral route and the parasitaemia was determined, before, 2, 4, and 6 h after drug administration, according to the method proposed by Filardy and Brener [14]. To induce parasitaemia, male NIH albino mice, 18 -20 g (ten mice per group) were inoculated intraperitoneally with 1 £ 10 3 blood trypomastigotes.…”