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.
CONTEXT: Doxorubicincardiotoxicity 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 doxorubicincardiotoxicity.
Authors: Beshay N Zordoky; M Judith Radin; Lois Heller; Anthony Tobias; Ilze Matise; Fred S Apple; Sylvia A McCune; Leslie C Sharkey Journal: Cardiooncology Date: 2016-03-15
Authors: Judit C Sági; Bálint Egyed; Andrea Kelemen; Nóra Kutszegi; Márta Hegyi; András Gézsi; Martina Ayaka Herlitschke; Andrea Rzepiel; Lili E Fodor; Gábor Ottóffy; Gábor T Kovács; Dániel J Erdélyi; Csaba Szalai; Ágnes F Semsei Journal: BMC Cancer Date: 2018-07-03 Impact factor: 4.430
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