Hydroxymethylnitrofurazone is active in a murine model of Chagas' disease.
The addition of a hydroxymethyl group to the antimicrobial drug nitrofurazone generated hydroxymethylnitrofurazone (NFOH), which had reduced toxicity when its activity against Trypanosoma cruzi was tested in a murine model of Chagas' disease. Four groups of 12 Swiss female mice each received 150 mg of body weight/kg/day of NFOH, 150 mg/kg/day of nitrofurazone (parental compound), 60 mg/kg/day of benznidazole (BZL), or the solvent as a placebo. Treatments were administered orally once a day 6 days a week until the completion of 60 doses. NFOH was as effective as BZL in keeping direct parasitemia at undetectable levels, and PCR results were negative. No histopathological lesions were seen 180 days after completion of the treatments, a time when the levels of anti-T. cruzi antibodies were very low in mice treated with either NFOH or BZL. Nitrofurazone was highly toxic, which led to an overall rate of mortality of 75% and necessitated interruption of the treatment. In contrast, the group treated with its hydroxymethyl derivative, NFOH, displayed the lowest mortality (16%), followed by the BZL (33%) and placebo (66%) groups. The findings of histopathological studies were consistent with these results, with the placebo group showing the most severe parasite infiltrates in skeletal muscle and heart tissue and the NFOH group showing the lowest. The present evidence suggests that NFOH is a promising anti-T. cruzi agent.
Davies
Carolina
C
Instituto de Patología Experimental, Facultad de Ciencias de la Salud, CONICET, Universidad Nacional de Salta, Avda. Bolivia 5150, Salta 4400, Argentina. carolinadavies@yahoo.com
Marino Cardozo
Rubén
R
Sánchez Negrette
Olga
O
Mora
María Celia
MC
Chung
Man Chin
MC
Basombrío
Miguel Angel
MA
D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy*; D005260:Female; D008099:Liver / Q000469:parasitology / Q000473:pathology; D051379:Mice; D015394:Molecular Structure; D018482:Muscle, Skeletal / Q000469:parasitology / Q000473:pathology; D009583:Nitrofurazone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D009593:Nitroimidazoles / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D011897:Random Allocation; D014344:Trypanocidal Agents / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000472:pathogenicity
D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C483719:hydroxymethylnitrofurazone; D009583:Nitrofurazone; C009999:benzonidazole