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.

Nad(p)h: quinone oxidoreductase-1 activity and increase of hydrogen peroxide production by NADPH oxidases are early biomarkers in doxorubicin cardiotoxicity.