The in vivo trypanocidal effect of the diterpene 5-epi-icetexone obtained from Salvia gilliesii.
The search for new compounds with trypanocidal activity is crucial for the treatment of Chagas' disease. Previous in vitro studies have shown that the diterpene 5-epi-icetexone (ICTX) is active against Trypanosoma cruzi. The aim of this work was to evaluate the effect of ICTX on the parasites in infected mice, in an experimental model that mimics the acute phase of the disease. Swiss albino mice were infected with T. cruzi and treated daily with 10mg/kg/day ICTX (i.p.). Infected mice and mice injected with either saline or the vehicle DMSO were used as controls. Animals' survival and parasitemia were monitored once a week and histological studies were made at necropsy by the 5th week after infection. It was observed that the administration of ICTX increased the survival of mice infected, and induced a significant decrease in the parasitemia, as compared to controls. A similar protective effect was observed when animals were treated orally with benznidazole (BZN, used as a control of antiparasitic effect). By the 5th week post-infection, the presence of amastigote nests was observed within the fibers of the cardiac and skeletal muscle in controls, but not in animals treated with either ICTX or BZN. In addition, inflammatory infiltrates were observed in the tissues of controls, but not in animals treated with the drugs. We conclude that ICTX has an antiparasitic effect against T. cruzi, thus constituting an interesting option for the treatment of Chagas' disease, alone or combined with other drugs.
Laboratorio de Biología y Fisiología Celular, Instituto de Histología y Embriología - CONICET, Facultad de Ciencias Médicas, UNCuyo, Argentina.
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Lozano
Instituto de Investigaciones en Ciencias de la Salud (INICSA), CONICET - Cátedra de Física Biomédica and Centro de Estudios e Investigación de la Enfermedad de Chagas y Leishmaniosis, Facultad de Ciencias Médicas, UNC, Córdoba, Argentina.
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Strauss
Laboratorio de Biología y Fisiología Celular, Instituto de Histología y Embriología - CONICET, Facultad de Ciencias Médicas, UNCuyo, Argentina.
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Spina
INTEQUI-CONICET, FQByF, UNSL, San Luis, Argentina.
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Cifuente
INTEQUI-CONICET, FQByF, UNSL, San Luis, Argentina.
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Tonn
Instituto de Investigaciones en Ciencias de la Salud (INICSA), CONICET - Cátedra de Física Biomédica and Centro de Estudios e Investigación de la Enfermedad de Chagas y Leishmaniosis, Facultad de Ciencias Médicas, UNC, Córdoba, Argentina.
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Rivarola
Laboratorio de Biología y Fisiología Celular, Instituto de Histología y Embriología - CONICET, Facultad de Ciencias Médicas, UNCuyo, Argentina. Electronic address: msosa@fcm.uncu.edu.ar.
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Sosa
D000284:Administration, Oral; D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage; D004195:Disease Models, Animal; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D006321:Heart / Q000469:parasitology; D051379:Mice; D018482:Muscle, Skeletal / Q000469:parasitology / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009593:Nitroimidazoles / Q000008:administration & dosage / Q000627:therapeutic use; D018512:Parasitemia / Q000188:drug therapy; D027544:Salvia / Q000737:chemistry*; D014344:Trypanocidal Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000187:drug effects*
D004224:Diterpenes; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C512853:icetexone; C009999:benzonidazole; D004121:Dimethyl Sulfoxide
Chagas' disease; Diterpenes; Natural compounds; Trypanosoma cruzi