INACTIVACIÓN FOTODINÁMICADE Trypanosoma cruzi POR EL TRATAMIENTO CON UNA AMINOPORFIRINA

VANESA PUENTE; MARIA DEL CARMEN MARTINEZ; GABRIELA ALVAREZ; ALCIRA BATLLE; FERNANDA M. FRANK; ELISA LOMBARDO

Rosario

Congreso; XXVI REUNION ANUAL DE LA SOCIEDAD ARGENTINA DE PROTOZOOLOGIA; 2013

SOCIEDAD ARGENTINA DE PROTOZOOLOGIA

Trypanosoma cruzi is the causative agent of Chagas ? disease, whichis a major endemic disease in Latin America. A nutritional characteristicof trypanosomatid protozoa is an absolute requirement of aheme-compound as a growth factor. However, hemin and relatedporphyrins have an important cytotoxic action through the generationof reactive oxygen species such as superoxide anion, hydrogenperoxide and the highly reactive hydroxyl radical; this effect isincreased by illumination with visible light. Previously, we studiedthe effect of hemin on growth and the antioxidant defense systemin T. cruzi epimastigote, and we demonstrated a correlation betweenhigher hemin concentrations in the culture medium and oxidativedamage in the cells. Although transmission of the disease is mainlyassociated with the feces of several species of triatomine bugs, bloodtransfusion is also important in the disease propagation. In this work, we evaluated the in vitro antiparasitic activityof the synthetic porphyrin 5,10,15,20-tetrakis[4-(3-N,N-dimethylaminepropoxy)phenyl]porphyrin(A4), on the epimastigote and trypomastigoteforms of T. cruzi. Additionally, the spectral propertiesof A4 were analyzed and an efficient method for its quantificationin different solvents, pHs and light conditions was developed. A4anti-parasitic activity against epimastigote (IC50 10.04 ± 0.4 μ M) wassimilar to the reference drug, benznidazole (7.40 ± 0.45 μ M). Anti-trypomastigoteactivity was evaluated in darkness and after 15 minutesof irradiation with a power density of 0.5 mW/cm2. Non-irradiatedparasites showed an IC50 of 11.64 ± 0.48 μ M, and after irradiation,this value was lower than 11.6 nM. Whole blood treatment with A4  +light did not affect red blood cells integrity, and after irradiation nofluorescence was detected in plasma and red blood cells. Takinginto account that A4 fluorescence is not masked with albumin, lackof signal could be attributed to the generation of a non fluorescentmetabolite and/or A4 phagocytosis by some blood cell. Cytotoxicactivity was also assayed on Vero cells, and CC50 was 267.4 mM and22.1 mM for non irradiated and 15 min irradiated cells, respectively. These results suggest that A4 can be used in blood banks tosterilize samples contaminated with T. cruzi.