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Determination of the therapeutic potential of natural antioxidants in experimental Chagas\' disease

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Maiara Voltarelli Providello
Total Authors: 1
Document type: Master's Dissertation
Press: Ribeirão Preto.
Institution: Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC)
Defense date:
Examining board members:
Sérgio de Albuquerque; Fernanda de Freitas Anibal; Carlos Renato Tirapelli
Advisor: Sérgio de Albuquerque

Seven million people are currently afflicted with Chagas\' disease. The endemic pathology in twenty one Latin America countries has as its etiological agent the protozoan Trypanosoma cruzi. It is necessary new therapeutic alternatives for this disease, because the drugs currently used have limited efficacy in the chronic phase, and have toxicity especially related to oxidative damage, due to the active principle of these drugs, in addition to being a natural part of the infection. Antioxidants have been studied in the therapy of the disease and the results seem promising. We evaluated ascorbic acid (AA), cyanocobalamin (B12) and melatonin (MEL) alone and in combination with a subclinical dose of benznidazole (BZ). Our aim was to determine the effects of antioxidants in the development of the acute phase of the disease. For this, we used Swiss mice, infected with T. cruzi, Y strain. Our results showed synergy in the association of AA+BZ10 to reduce parasitemia; concentration of intracellular ROS (Reactive oxygen species) and the levels of TBARS (Thiobarbituric Acid Reactive Substances) in the heart were also decreased. AA and AA+BZ10 were effective in reducing cardiac parasitism detected by qPCR and histological analyzes. The AA+BZ10 group presented reduction in cardiac inflammatory infiltrate. B12 and B12+BZ10 were not effective in reducing parasitemia. B12+BZ10 reduced cardiac parasitism and cardiac inflammatory infiltrate; furthermore it acted against intracellular ROS. In group B12 an increase in SOD (Superoxide dismutase) activity was detected. MEL and MEL+BZ10 reduced parasitemia, but were not effective in decreasing intracellular ROS. Levels of cardiac TBARS were reduced in the MEL group and an increase in SOD activity was observed in MEL and MEL+BZ10. In these groups, reduction in parasitism and inflammatory infiltrate were observed in the heart. Our results show that the use of antioxidants can be benefical, either by trypanocidal action or by attenuation of oxidative damage, which in the long term may result in greater preservation of tissue damage. (AU)

FAPESP's process: 16/03632-6 - Determining the therapeutic potential of natural antioxidants in the experimental Chagas disease
Grantee:Maiara Voltarelli Providello
Support Opportunities: Scholarships in Brazil - Master