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

Abstract

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)