RESUMEN
Trypanosoma cruzi is the causative agent of Chagas' disease, a parasitic disease that remains a serious health concern with unsatisfactory treatment. Drugs that are currently used to treat Chagas' disease are partially effective in the acute phase but ineffective in the chronic phase of the disease. The aim of the present study was to evaluate the antitrypanosomal activity and morphological, ultrastructural and biochemical alterations induced by a new molecule, 4-nitrobenzaldehyde thiosemicarbazone (BZTS), derived from S-(-)-limonene against epimastigote, trypomastigote and intracellular amastigote forms of T. cruzi. BZTS inhibited the growth of epimastigotes (IC50 = 9·2 µ m), intracellular amastigotes (IC50 = 3·23 µ m) and inhibited the viability of trypomastigotes (EC50 = 1·43 µ m). BZTS had a CC50 of 37·45 µ m in LLCMK2 cells. BZTS induced rounding and distortion of the cell body and severely damaged parasite mitochondria, reflected by extensive swelling and disorganization in the inner mitochondrial membrane and the presence of concentric membrane structures inside the organelle. Cytoplasmic vacuolization, endoplasmic reticulum that surrounded organelles, the loss of mitochondrial membrane potential, and increased mitochondrial O2 â¢- production were also observed. Our results suggest that BZTS alters the ultrastructure and physiology of mitochondria, which could be closely related to parasite death.
Asunto(s)
Ciclohexenos/química , Estadios del Ciclo de Vida/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Terpenos/química , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacos , Animales , Benzaldehídos/química , Benzaldehídos/farmacología , Línea Celular , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/patología , Retículo Endoplásmico/ultraestructura , Células Epiteliales/efectos de los fármacos , Células Epiteliales/parasitología , Estadios del Ciclo de Vida/fisiología , Limoneno , Macaca mulatta , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/patología , Mitocondrias/ultraestructura , Superóxidos/agonistas , Superóxidos/metabolismo , Tiosemicarbazonas/química , Tiosemicarbazonas/farmacología , Tripanocidas/química , Trypanosoma cruzi/crecimiento & desarrollo , Trypanosoma cruzi/metabolismo , Trypanosoma cruzi/ultraestructuraRESUMEN
Cancer chemotherapy is associated with neutropenia and impaired neutrophil function. This study aimed to investigate whether supplementation with low dose fish oil (FO), providing n-3 polyunsaturated fatty acids, in cancer patients receiving chemotherapy after surgical tumor (mainly gastrointestinal) removal is able to improve the function of blood neutrophils. Patients (n = 38) receiving chemotherapy (5-fluorouracil and leucovorin) were randomized into two groups; one group (control) did not receive a supplement, while the other group (FO) received 2 g FO/day for 8 weeks; the FO provided 0.3 g eicosapentaenoic acid plus 0.4 g docosahexaenoic acid per day. Patients in the control group lost an average of 2.5 kg of weight over the 8 weeks of the study. The number of blood polymorphonuclear cells (PMNC), mainly neutrophils, and their functions (phagocytosis and hydrogen peroxide production) decreased in the control group (average decreases of approximately 30, 45 and 17%, respectively). FO prevented these decreases and actually increased body weight (average of 1.7 kg weight gain; p < 0.002 vs. control group), PMNC number (average 29% increase), phagocytosis (average 14% increase) and superoxide production (average 28% increase). FO may be useful in preventing chemotherapy-induced decline in neutrophil number and function.