Efficacy of the bisbenzylisoquinoline alkaloids in acute and chronic Trypanosoma cruzi murine model

We have shown previously that daphnoline and cepharanthine are active against Trypanosoma cruzi and inhibited trypanothione reductase. The effects of oral treatments with daphnoline, cepharanthine and benznidazole were examined in Balb/c mice infected with T. cruzi acutely and chronically. In acute...

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Bibliographic Details
Published in:International journal of antimicrobial agents 2000, Vol.13 (3), p.189-195
Main Authors: Fournet, Alain, Rojas de Arias, Antonieta, Ferreira, Maria Elena, Nakayama, Hector, Torres de Ortiz, Susana, Schinini, Alicia, Samudio, Margarita, Vera de Bilbao, Ninfa, Lavault, Maria, Bonté, Frédéric
Format: Article
Language:English
Subjects:
Acute Disease
Administration, Oral
Alkaloids - administration & dosage
Alkaloids - pharmacology
Animals
benznidazole
Benzylisoquinolines
Bisbenzylisoquinoline
bisbenzylisoquinoline alkaloids
Cepharanthine
Chagas Disease - drug therapy
Chagas’ disease
Chronic Disease
Daphnoline
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Experimental treatment
Female
Immunoblotting
Isoquinolines - administration & dosage
Isoquinolines - pharmacology
Male
Mice
Mice, Inbred BALB C
Nitroimidazoles - administration & dosage
Nitroimidazoles - pharmacology
Parasitemia - drug therapy
Trypanocidal Agents - administration & dosage
Trypanocidal Agents - pharmacology
Trypanosoma cruzi
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Summary:We have shown previously that daphnoline and cepharanthine are active against Trypanosoma cruzi and inhibited trypanothione reductase. The effects of oral treatments with daphnoline, cepharanthine and benznidazole were examined in Balb/c mice infected with T. cruzi acutely and chronically. In acute infections, parasitaemia was significantly reduced in the daphnoline-treated mice compared with controls and benznidazole-treated mice. The parasitological cure rate was increased in mice treated with daphnoline. Fifty days after infection, the negative serological response in both models was significantly different for the three tested drugs. Daphnoline showed the highest negative serological rate (48%). In chronically infected mice treated with daphnoline, we were unable to detect parasites in 70% of mice. The results obtained of oral treatment of daphnoline suggest that this bisbenzylisoquinoline may be useful in the treatment of acute and chronic Chagas’ disease. This was not seen with cepharanthine, an excellent trypanothione reductase inhibitor.
ISSN:0924-8579
1872-7913
DOI:10.1016/S0924-8579(99)00117-X