Mitochondrial Protection by Astaxanthin Reduces Toxicity Caused by H2O2 and Doxorubicin in Human Cardiomyocytes

Astaxanthin (AST) is a xanthophyll carotenoid known for its cardioprotective effects. In this study, we investigated the impact of AST on the survival of AC16 human cardiomyocytes under cardiotoxic conditions induced by hydrogen peroxide (H₂O₂) and doxorubicin (DOX). We assessed a series of parameters associated with cell death signaling, including: changes in cytosolic Ca²⁺ levels and reactive oxygen species (ROS) production; alterations in mitochondrial function (membrane potential ΔΨm and the content of key subunits of complexes I and II); and the levels of key apoptotic and ER stress markers. Our findings show that AST prevented the cytotoxic effects of both H₂O₂ and DOX. In the presence of AST, the number of viable cells increased, while Ca²⁺ levels, ROS production, and ΔΨm remained comparable to those in the control group. Furthermore, AST prevented the H₂O₂-induced decrease in the levels of the main subunits of respiratory chain complexes I and II. AST prevented the H₂O₂-induced increase in the levels of apoptotic caspases-8 and -3. It also protected against ER stress by counteracting the H₂O₂-mediated upregulation of BIP, CHOP, and ERO1α proteins. These results lead us to conclude that AST exerts a protective effect by inhibiting mitochondrial dysfunction.