Photodinamic inactivation of Trypanosoma Cruzi by the Aminoporphyrin A4

MARTíNEZ, MARIA DEL CARMEN; MORA, J; ALVAREZ, GABRIELA; DURANTINI E; FUKUDA, HAYDéE; BATLLE, ALCIRA; ROSSETTI, MARIA VICTORIA; LOMBARDO ME

Lucerna

Congreso; INTERNATIONAL CONGRESS ON PORPHYRINS AND PORPHYRIAS 2013; 2013

Swiss Medical Association

Trypanosoma cruzi is the causative agent of Chagas ? disease, which is a major endemic disease in Latin America. A nutritional characteristic of trypanosomatid protozoa is an absolute requirement of a heme-compound as a growth factor. However, hemin and related porphyrins have an important cytotoxic action through the generation of reactive oxygen species such as superoxide anion, hydrogen peroxide and the highly reactive hydroxyl radical; this effect is increased by illumination with visible light. Previously, we studied the effect of hemin on growth and the antioxidant defense system in T. cruzi epimastigote, and we demonstrated a correlation between higher hemin concentrations in the culture medium and oxidative damage in the cells. Although transmission of the disease is mainly associated with the feces of several species of triatomine bugs, blood transfusion is also important in the disease propagation. In this work, we evaluated the in vitro antiparasitic activity of the synthetic porphyrin 5,10,15,20-tetrakis[4-(3-N,N-dimethylaminepropoxy) phenyl]porphyrin (A4), on the epimastigote and trypomastigote forms of T. cruzi. Additionally, the spectral properties of A4 were analyzed and an efficient method for its quantification in different solvents, pHs and light conditions was developed. A4 anti-parasitic activity against epimastigote (IC50 10.04 ± 0.4 μ M) was similar to the reference drug, benznidazole (7.40 ± 0.45 μ M). Anti-trypomastigote activity was evaluated in darkness and after 15 minutes of irradiation with a power density of 0.5 mW/cm2. Non-irradiated parasites 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 no fluorescence was detected in plasma and red blood cells. Taking into account that A4 fluorescence is not masked with albumin, lack of signal could be attributed to the generation of a non fluorescent metabolite and/or A4 phagocytosis by some blood cell. Cytotoxic activity was also assayed on Vero cells, and CC50 was 267.4 mM and 22.1 mM for non irradiated and 15 min irradiated cells, respectively. These results suggest that A4 can be used in blood banks to sterilize samples contaminated with T. cruzi.