Related Experiment Video
Updated: May 3, 2026
A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish
Published on: June 7, 2018
The decrease of NAD(P)H:quinone oxidoreductase 1 activity and increase of ROS production by NADPH oxidases are early
Ricardo Lagoa1, Carlos Gañán, Carmen López-Sánchez
1ESTG-Polytechnic Institute of Leiria , Leiria , Portugal .
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.
Insights
Early changes in doxorubicin cardiotoxicity involve increased lipid oxidation and hydrogen peroxide production, preceding mitochondrial dysfunction. These oxidative stress markers signal the onset of heart damage.
Area of Science:
- Biochemistry
- Cardiology
- Toxicology
Background:
- Doxorubicin-induced cardiotoxicity is a complex condition with multifactorial progression.
- Understanding early biochemical events is crucial for mitigating cardiac damage.
Purpose of the Study:
- To identify early biochemical mechanisms driving sustained cellular bioenergetic imbalance in doxorubicin cardiotoxicity.
- To establish early diagnostic biomarkers for doxorubicin-induced heart damage.
Main Methods:
- Rats were treated with doxorubicin (20 mg/kg).
- Temporal evolution of selected biochemical markers was measured.
- Key markers included oxidative stress indicators and bioenergetic parameters.
Main Results:
- Doxorubicin increased lipid oxidation, catalase activity, and hydrogen peroxide (H₂O₂) production via Nox-NADPH oxidases.
- Quinone oxidoreductase-1 (NQO1) was downregulated early.
- Changes in reduced glutathione, protein carbonyls, and protein nitrotyrosines followed.
- Mitochondrial and myofibrillar bioenergetic alterations were detected only after oxidative imbalance was established.
Conclusions:
- Downregulation of quinone oxidoreductase-1 activity and increased hydrogen peroxide production by NADPH oxidases are early biomarkers.
- These oxidative stress markers precede detectable changes in mitochondrial and myofibrillar bioenergetics.
- Identifying these early events may allow for timely intervention against doxorubicin cardiotoxicity.
