The decrease of NAD(P)H:quinone oxidoreductase 1 activity and increase of ROS production by NADPH oxidases are early biomarkers in doxorubicin cardiotoxicity

Context: Doxorubicin cardiotoxicity displays a complex and multifactorial progression. Objective: Identify early biochemical mechanisms leading to a sustained imbalance of cellular bioenergetics. Methods: Measurements of the temporal evolution of selected biochemical markers after treatment of rats with doxorubicin (20 mg/kg body weight). Results: Doxorubicin treatment increased lipid oxidation, catalase activity and production of H2O2 by Nox-NADPH oxidases, and down-regulated NAD(P)H: quinone oxidoreductase-1 prior eliciting changes in reduced glutathione, protein carbonyls and protein nitrotyrosines. Alterations of mitochondrial and myofibrillar bioenergetics biomarkers were detected only after this oxidative imbalance was established. Conclusions: NAD(P) H: quinone oxidoreductase-1 activity and increase of hydrogen peroxide production by NADPH oxidases are early biomarkers in doxorubicin cardiotoxicity.