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Antiparasitic activity of risedronate in a murine model of acute Chagas' disease.

Abstract：

:We report the results of a study on the activity of the farnesyl-pyrophosphate synthase inhibitor risedronate (Ris) in a murine model of acute Chagas' disease. This compound displays rapid, cytocidal activity in vitro against Trypanosoma cruzi, but its in vivo activity had not been investigated previously. A murine model of acute Chagas' disease was used, in which experimental animals were infected with 10(3) trypomastigotes and intravenous treatment was started 24 h post-infection. In this model, Ris, at doses as low as 1 mg/kg per day given for 7 days, induced > 90% reductions in parasitaemia and increased very significantly (P = 0.001) the survival of treated animals. Higher doses (up to 10 mg/kg per day) led to further reductions in parasitaemia and mortality, with no deleterious effects on weight gain and general physical condition of the treated animals. There was no relapse of parasitaemia after discontinuation of treatment, suggesting trypanocidal, rather than trypanostatic, activity. This interpretation was confirmed by the almost complete disappearance of amastigote nests in the hearts of treated animals. However, no parasitological cures were observed in infected animals that received the bisphosphonate, probably due to the short treatment period. Taken together, these results indicate that Ris could be a useful lead compound for the development of new drugs effective against Chagas' disease.

journal_name

Int J Antimicrob Agents

journal_title

International journal of antimicrobial agents

authors

Garzoni LR,Waghabi MC,Baptista MM,de Castro SL,Meirelles Mde N,Britto CC,Docampo R,Oldfield E,Urbina JA

doi

10.1016/j.ijantimicag.2003.07.019

subject

Has Abstract

pub_date

2004-03-01 00:00:00

pages

286-90

issue

3

eissn

0924-8579

issn

1872-7913

pii

S0924-8579(03)00407-2

journal_volume

23

pub_type

杂志文章

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