Inhibition of heme aggregation by chloroquine reduces Schistosoma mansoni infection.
Adult Schistosoma mansoni digest large amounts of host hemoglobin and release potentially toxic heme inside their guts. We have previously demonstrated that free heme in S. mansoni is detoxified through aggregation, forming hemozoin (Hz). Possible mechanisms of heme aggregation and the effects of chloroquine (CLQ) on formation of Hz and on the viability of this parasite have now been investigated. Different fractions isolated from S. mansoni, such as crude whole-worm homogenates, total lipid extracts, and Hz itself promoted heme aggregation in vitro in a CLQ-sensitive manner. Treatment of S. mansoni-infected mice with CLQ led to remarkable decreases in total protein, Hz content, and viability of the worms, as well as in parasitemia and deposition of eggs in mouse livers. These results indicate that inhibition of formation of Hz in S. mansoni, by CLQ, led to an important decrease in the overall severity of experimental murine schistosomiasis. Taken together, the results presented here suggest that formation of Hz is a major mechanism of heme detoxification and a potential target for chemotherapy in S. mansoni.
Oliveira
Marcus F
MF
Departamento de Bioquimica Medica, Universidade Federal do Rio de Janeiro, Cidade Universitaria, Rio de Janeiro, Brazil. maroli@bioqmed.ufrj.br
d'Avila
Joana C P
JC
Tempone
Antonio J
AJ
Soares
Juliana B R Correa
JB
Rumjanek
Franklin D
FD
Ferreira-Pereira
Antonio
A
Ferreira
Sergio T
ST
Oliveira
Pedro L
PL
D000818:Animals; D002458:Cell Fractionation; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use*; D015331:Cohort Studies; D004195:Disease Models, Animal; D015195:Drug Design; D005260:Female; D006418:Heme / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006420:Hemeproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D008099:Liver / Q000469:parasitology; D051379:Mice; D010270:Parasite Egg Count; D018512:Parasitemia; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D012552:Schistosomiasis / Q000188:drug therapy*
D006420:Hemeproteins; C020753:hemozoin; D006418:Heme; D002738:Chloroquine