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

AbstractContext: 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.