Azasterols impair Giardia lamblia proliferation and induces encystation.

Biochem Biophys Res Commun

Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Published: November 2007

The effects of sterol biosynthesis inhibitors on growth and fine structure of Giardia lamblia P1 strain cultures were analyzed. Azasterols demonstrated high efficacy in killing cells. The IC(50) values for 22,26-azasterol and 24(R,S),25-epiminolanosterol were 7muM and 170nM, respectively. Morphological analysis showed that azasterols induced changes in G. lamblia ultrastructure. The most significant alterations were: (a) considerable increase of the size of the peripheral vesicles, which are part of the parasite endosomal-lysosomal system; (b) appearance of autophagosomal structures; and (c) induction of differentiation, followed by an abnormal enlargement of encystation secretory vesicles. We propose that azasterols are effective chemotherapeutic drugs against Giardia lamblia in vitro and may have another target in cells besides sterol biosynthesis.

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http://dx.doi.org/10.1016/j.bbrc.2007.08.174DOI Listing

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