Doxorubicin-induced mitochondial changes and Alda-1 protective potential in cardiac cells

• Grant number: 21/14056-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2022
• End date: December 31, 2022
• Field of knowledge: Biological Sciences - Genetics - Mutagenesis
• Principal Investigator: Daisy Maria Favero Salvadori
• Grantee: Leandro Lopes Silva
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Doxorubicin (DOX) is an anthracycline isolated from the actinobacteria Streptomyces peucetius and is widely used in anticancer therapy. However, despite its effectiveness, DOX can promote cardiotoxicity that limits chemotherapy and reduces the quality of life of patients. Scientific literature suggests that DOX-induced toxicity may be associated with mitochondrial dysfunction, which results in increased production of reactive oxygen species (ROS), mitochondrial DNA damage, and decreased energy production. In this context, the mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2) plays an important role, as it acts in protection against the effects of oxidative stress. However, it is known that DOX can reduce the activity of ALDH2, making the cardiac tissue susceptible to alterations resulting from processes such as lipoperoxidation. Recognized as an important activator of ALDH2, Alda-1 is a potential therapeutic agent that has been tested against the side effects of DOX. Given these premises, this study aims to investigate whether mitochondrial mechanisms are associated with DOX-induced cardiotoxicity and the possible protective action of Alda-1. More specifically, cell viability, mitochondrial DNA damage, mitochondrial ROS generation, and mitochondrial membrane mass and potential will be evaluated in cardiomyoblasts treated in vitro with DOX and Alda-1. It is expected that the results can contribute to the understanding of the mechanism of cardiotoxicity of DOX, as well as the potential of Alda-1 for the protection of cardiac cells.(AU)