title: The decrease of NAD(P)H:quinone oxidoreductase 1 activity and increase of ROS production by NADPH oxidases are early biomarkers in doxorubicin cardiotoxicity.
abstract: BACKGROUND
  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
  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
  
  quinone oxidoreductase-1 activity and increase of hydrogen peroxide production by NADPH oxidases are early biomarkers in doxorubicin cardiotoxicity.
authors: ESTG-Polytechnic Institute of Leiria , Leiria , Portugal .
authors: Ricardo
authors: R
authors: Lagoa
authors: Carlos
authors: C
authors: Gañán
authors: Carmen
authors: C
authors: López-Sánchez
authors: Virginio
authors: V
authors: García-Martínez
authors: Carlos
authors: C
authors: Gutierrez-Merino
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000201:enzymology; D004317:Doxorubicin / Q000633:toxicity*; D004734:Energy Metabolism / Q000187:drug effects; D015227:Lipid Peroxidation; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D050050:Protein Carbonylation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D004317:Doxorubicin; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat