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Cardiotoxicity induced by doxorubicin in Wistar rats and the cardioprotective potential of Alda-1

Grant number: 14/09740-0
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2014
Effective date (End): February 28, 2019
Field of knowledge:Biological Sciences - Genetics - Mutagenesis
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Daisy Maria Favero Salvadori
Grantee:Leonardo da Cunha Menezes Souza
Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Associated scholarship(s):17/03180-0 - In vitro cardiotoxicity induced by doxorubicin and cardioprotective potential of Alda-1, BE.EP.DR


Cardiotoxicity induced by doxorubicin (DOX), an anthracycline isolated from Streptomyces peucetius, is one of the main secondary pathophisiological events related to this antineoplasic compound. Cell death resulting from the toxic conditions is associated to deregulate metabolic mechanisms. Intracellular calcium flux and mitochondrial permeability seem to be important factors for cell death. Reactive oxygen species can form aldehydes on the cells membranes, which alter the mitochondrial redox state and form adducts with proteins, inhibiting their activities. However, there is a specific class of enzymes, the aldehydes dehydrogenases (ALDH2), which removes the aldehydes from the cells and reduces their deleterious effects. The present study aims to evaluate the mechanism of cardiotoxicity induced by doxorrubicin and also the cardioprotective potential of ALDA-1. We will evaluate: the expression of genes related to polyunsaturated fatty acid oxidation by PCR arrays, and to calcium channels (PPI and C1QBP) and to cell death (Bax and Bcl2) by qPCR-RT; apoptosis and necrosis rates by flow cytometry; activity of ALDH2 gene and its respective enzyme and microRNAS associated with ALDH2 regulation. We expect the set of results may contribute to the elucidation of the cardiotoxic potential of doxorrubicin and also for establishing efficient strategies to reduce the side effects of DOX on the heart. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MENEZES SOUZA, LEONARDO DA CUNHA; FERNANDES, FABIO HENRIQUE; PRESTI, PAULA TORRES; ANJOS FERREIRA, ANA LUCIA; FAVERO SALVADORI, DAISY MARIA. Effect of doxorubicin on cardiac lipid metabolism-related transcriptome and the protective activity of Alda-1. European Journal of Pharmacology, v. 898, . (14/09740-0)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SOUZA, Leonardo da Cunha Menezes. Cardiotoxicity induced by doxorubicin in Wistar rats and the cardioprotective potential of Alda-1. 2019. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu Botucatu.

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