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ACTIVITIES OF PSILOSTACHYIN A AN CYNAROPICRIN AGAINST TRYPANOSOMA CRUZI IN VITRO AND IN VIVO
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In vitro and in vivo activities against Trypanosoma cruzi were evaluated for two sesquiterpene lactones: psilostachyin A and cynaropicrin.
Cynaropicrin had previously been shown to potently inhibit African trypanosomes in vivo, and psilostachyin A had
been reported to show in vivo effects against T. cruzi, albeit in another test design. In vitro data showed that cynaropicrin was
more effective than psilostachyin A. Ultrastructural alterations induced by cynaropicrin included shedding events, detachment
of large portions of the plasma membrane, and vesicular bodies and large vacuoles containing membranous structures, suggestive
of parasite autophagy. Acute toxicity studies showed that one of two mice died at a cynaropicrin dose of 400 mg/kg of body
weight given intraperitoneally (i.p.). Although no major plasma biochemical alterations could be detected, histopathology demonstrated
that the liver was the most affected organ in cynaropicrin-treated animals. Although cynaropicrin was as effective as
benznidazole against trypomastigotes in vitro, the treatment (once or twice a day) of T. cruzi-infected mice (up to 50 mg/kg/day
cynaropicrin) did not suppress parasitemia or protect against mortality induced by the Y and Colombiana strains. Psilostachyin
A (0.5 to 50 mg/kg/day given once a day) was not effective in the acute model of T. cruzi infection (Y strain), reaching 100% animal
mortality. Our data demonstrate that although it is very promising against African trypanosomes, cynaropicrin does not
show efficacy compared to benznidazole in acute mouse models of T. cruzi infection.
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