Toxic and therapeutic effects of Nifurtimox and Benznidazol on Trypanosoma cruzi ex vivo infection of human placental chorionic villi explants.
Nifurtimox (Nfx) and Benznidazole (Bnz) are the only available drugs in use for the treatment of Chagas disease. These drugs are recommended but not fully validated in evidence-based medicine and reports about the differential toxicity of both drugs are controversial. Here, we evaluated the toxic and therapeutic effects of Nfx and Bnz on human placental chorionic villi explants (HPCVE) during ex vivo infection of Trypanosoma cruzi, performing histopathological, histochemical, immunohistochemical as well as immunofluorescence analysis of the tissue. Additionally, we determined the effect of both drugs on parasite load by real time PCR. Bnz prevents the parasite induced tissue damage in ex vivo infected HPCVE compared to Nfx, which is toxic per se. The presence of T. cruzi antigens and DNA in infected explants suggests that these drugs do not impair parasite invasion into the HPCVE. Additionally, our results confirm reports suggesting that Bnz is less toxic than Nfx and support the need for the development of more effective and better-tolerated drugs.
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago de Chile 8380453, Chile.
Gemma
G
Rojo
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago de Chile 8380453, Chile.
Christian
C
Castillo
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago de Chile 8380453, Chile.
Juan
J
Duaso
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago de Chile 8380453, Chile.
Ana
A
Liempi
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago de Chile 8380453, Chile.
Daniel
D
Droguett
Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago de Chile 8380453, Chile.
Norbel
N
Galanti
Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago de Chile 8380453, Chile.
Juan Diego
JD
Maya
Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago de Chile 8380453, Chile.
Rodrigo
R
López-Muñoz
Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago de Chile 8380453, Chile. Electronic address: ukemmerling@med.uchile.cl.
Ulrike
U
Kemmerling
D000977:Antiparasitic Agents / Q000009:adverse effects / Q000494:pharmacology*; D002824:Chorionic Villi / Q000469:parasitology*; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008856:Microscopy, Fluorescence; D009547:Nifurtimox / Q000009:adverse effects / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000009:adverse effects / Q000494:pharmacology*; D059208:Parasite Load; D010920:Placenta / Q000469:parasitology*; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction; D014349:Trypanosoma cruzi / Q000187:drug effects*
D000977:Antiparasitic Agents; D009593:Nitroimidazoles; D009547:Nifurtimox; C009999:benzonidazole
Benznidazole; Human placental chorionic villi explants; Nifurtimox; Toxicity