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Nogueira 2014 Abstract IOC 2014-04 Schroecken

From Bioblast
Nogueira NP, Baldow QCS, Costa DSS, Domingos J, Laranja GAT, Costa PRR, Dias AG, Paes MC (2014) The effect of nitrones upon clinically relevant forms of Trypanosoma cruzi. Mitochondr Physiol Network 19.02.

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Nogueira NP, Baldow QCS, Costa DSS, Domingos J, Laranja GAT, Costa PRR, Dias AG, Paes MC (2014)

Event: MiPNet19.02 IOC88

Trypanosoma cruzi, the etiological agent of Chagas disease, is transmitted during the triatomine vector blood meal in the vertebrate host. This parasite has a complex life cycle which alternates between its insect vector, and vertebrate hosts, including humans. Along its path through different compartments to the final region of the triatomine digestive tract, the rectum, T. cruzi experiences extreme environmental changes as it alternates between insect and mammalian hosts. Therefore, the parasite must survive changes in pH, nutrients and osmolality as well as redox status that can modulate the parasite life cycle, as well as precisely and quickly respond to a wide spectrum of stressors and modulators. Moreover, unlike other organisms, T cruzi, has a single mitochondrion. Mitochondria are organelles implicated not only in aerobic ATP synthesis, but are also involved in the cellular redox balance, representing one of the major sources of reactive oxygen species (ROS) in the cell. Due to its complex life cycle and its different hosts and various host environments, T. cruzi is constantly exposed to reactive oxygen species (ROS). However, despite the efforts, deficiencies in the treatment justify the search for new chemotherapeutic options against Chagas disease. Nitrones have been widely used in biochemistry to trap and stabilize free radicals for the purpose of their identification and characterization. Many studies have demonstrated that nitrones present potent pharmacologic activities in models of a number of aging and oxidative stress-related diseases, most notably the neurodegenerative diseases of stroke and Alzheimer's disease. Yet, although these molecules present antioxidant properties as well as protective role against pathogen infections, little is known about the effects of these molecules in the parasites energy metabolism modulation. Therefore, we intent to test the effect of nitrones upon mitochondrial respiration in digitonin-permeabilized parasites using high-resolution respirometry (HRR). We will test OXPHOS in various parasite forms, performing oxygen consumption measurements in Routine conditions, as well as in the presence of ET-pathway substrates and inhibitors. Using this approach, we aim to provide information on the mode of action of selected nitrones with trypanocial action against important forms of the parasite life cycle, without harming mammal cells.

Keywords: Trypanosoma cruzi, ROS, chemotherapy, bioenergetics, nitrone

O2k-Network Lab: BR Rio de Janeiro Paes MC


Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Infectious  Stress:Oxidative stress;RONS  Organism: Mouse, Protists  Tissue;cell: Macrophage-derived  Preparation: Intact organism, Intact cells, Permeabilized cells 



HRR: Oxygraph-2k 


Nogueira NP (1), Baldow QCS (1), Costa DSS (2),Domingos J (2), Laranja GAT (1), Costa PRR (3), Dias AG (2) and Paes MC (1)

1 Instituto de Biologia Roberto Alcântara Gomes - Departamento de Bioquímica – Universidade do Estado do Rio de Janeiro – RJ - Brasil. 2 Departamento de Química Orgânica - Universidade do Estado do Rio de Janeiro- RJ - Brasil. 3 NPPN-Universidade Federal do Rio de Janeiro-RJ-Brasil

Supported by CNPq, INCT-EM and FAPERJ