Dados do Trabalho

Título

Schistosomicidal evaluation of 13-methyl-(1,3)benzodioxol(5,6-c)-1,3-dioxolane(4,5i)phenanthridinium (Sanguinarine - Alkaloid) against different evolutionary stages of Schistosoma mansoni

Introdução

Praziquantel (PZQ) is the only drug to control/treatment schistosomiasis, but it targets adult worms, not being effective against schistosomula and young worms. Alkaloids have broad biological and pharmacological activity, including antiparasitic.

Objetivo (s)

We aimed to explore the in vitro schistosomicidal action of sanguinarine (SA) against different evolutionary stages of S. mansoni.

Material e Métodos

Cercariae from S. mansoni (BH strain) were mechanically transformed into schistosomula. Mice were infected with cercariae to obtain young worms and adult couples recovered through perfusion of the hepatic portal system/mesenteric vessels after the 21st and 45th day of infection, respectively. The different evolutionary stages were distributed in culture plates (70 schistosomula, 30 young worms or 2 adult couples/well in sextuplicate) and incubated at 1 to 25 μM of SA. The worms were monitored after 3, 6, 12 and 24h to assess mortality, change in motility and cell viability of the worms by the MTT assay. The different phases were incubated in RPMI medium or 10 µM PZQ to form negative and positive controls, respectively.

Resultados e Conclusão

For all evolutionary stages the negative control exhibited typical motility and topography and peristalsis. PZQ did not cause mortality in schistosomula and young worms, only reduced motility, whereas against adult worms mortality was 94% after 24h. On the other hand, between 7.5 and 25 μM SA caused 100% mortality in schistosomula and young worms just after 3h, for this interval mortality in adults was 87 and 69% at 25 and 20 μM, respectively. Soon after 3h, 4 and 5 μM caused 26 and 100% of mortality in schistosomula, respectively, and
after 24h total lethality in 4, 3, 2 and 1 μM. After 24h, 4 and 5 μM of SA caused mortality of 90% of young worms and 3, 2 and 1 μM caused 46, 33 and 0%. Total couple mortality was only achieved after 6h in 25 μM SA, 12h with 20 μM and 24h in 15 μM. For adult couples lower concentrations did not cause mortality. SA reduced the cell viability of different stages in a dose-dependent manner between 93 and 20%, where for higher concentrations the reduction was greater than PZQ, which reduced in 32 and 75% for young worms and adult couples, respectively. SA caused mortality, in vitro, at low concentrations and short incubation period especially against the immature stages of schistosomula and young worms of S. mansoni, stages that PZQ has no activity.

Palavras-chave

Alkaloids, schistosomicidal, immature stages

Agradecimentos

CAPES, FACEPE