Hydroximethylnitrofurazone: in vivo evaluation of its trypanocidal and leishmanocidal activity

DAVIES, CAROLINA; GARCÍA BUSTOS, MARÍA FERNANDA; CHUNG MANCHIN; BASOMBRÍO MIGUEL ANGEL

Armação dos Búzios, Rio de Janeiro, Brasil.

Congreso; XIII International Congress of Protistology, XXV Meeting of the Brazilian Society of Protozoology, XXVI Annual Meeting on Basic Research in Chagas Disease.; 2009

Sociedade Brasileira de Protistologia

Chagas disease is treated with Benznidazol (BZL) or Nifurtimox, both toxic and ineffective in patients during the chronic phase. Similarly, meglumine antimoniate (MA) which cures American Tegumentary Leishmaniasis (ATL) presents adverse effects and numerous cases of resistance. In completely randomized murine models of Chagas disease and ATL we evaluated the new compound hydroximethylnitrofurazone (NFOH) as an alternative to current treatment to these maladies. For Chagas disease, 48 Swiss female mice were infected intraperitoneally ith 1000 trypomastigote forms/mouse. From day 5 post-infection, they received 60 oral doses of 60 mg/Kg/day BZL, 150 mg/Kg/day NF (parental compound), or 150 mg/Kg/day NFOH, in 5% NaCl - 9 % Tween 80 suspension (control group). At 30 and 240 days post-infection conventional PCR and ELISA were performed. Circulating parasites were detected in the control group, causing 66% mortality, compared to 0% NFOH and 10% BZL. PCR and IgG titres were negative at 240 days post-treatment in treated mice; the control group remained positive. While NF was lethal at the administered dose, NFOH caused lower mortality than BZL being also effective in controlling the disease. For ATL model, 35 Swiss male mice were subcutaneously infected in the right footpad with 10000 Leishmania (L) amazonensis promastigote forms/mouse. At 5 days post-infection, they received 30 doses of 300 mg/Kg/day, 150 mg/Kg/day NFOH, or 200 mg/Kg/day MA in 5% NaCl - 9 % Tween 80 (control group). Granulome size was measured from days 49 to 126 post-infection. Lesion development was inhibited between days 49 - 69 (NFOH, 150 mg/Kg/day), and 49 – 63 (MA). At later dates, lesions were similar to those of the untreated mice. 300 mg/Kg/day NFOH was similar to the control group. Although NFOH showed promising results as an anti-chagasic, its effect as a leishmanocidal drug is not so clear. Grants: Bunge y Born, Florencio Fiorini, CONICET.