Acute administration of epirubicin induces myocardial depression in isolated rat heart and production of radical species evaluated by electron spin resonance spectroscopy.
The aim of our study was to evaluate the acute effect of epirubicin (EPI), an anthracycline anticancer drug, on the evolution of cardiac functional parameters and production of reactive oxygen/nitrogen species (RONS). Isolated perfused rat hearts were subjected to 70 minutes of EPI (10.3 microM) infusion and to 5 minutes of isoproterenol (ISO, 0.1 microM) at the end of the protocol. Coronary flow (CF), left ventricular developed pressure (LVDP), and lactate dehydrogenase (LDH) release in the coronary effluents were evaluated throughout the protocol. RONS were detected in the coronary effluents by electron spin resonance spectroscopy with a spin probe, 1-hydroxy-3-carboxy-pyrrolidine (CP-H, 0.1 mM). EPI induced a reduction in CF and in LVDP (P < 0.001). ISO infusion enhanced CF and RPP in the control group; in the EPI group, these increases were significantly impaired. Release of LDH was significantly increased during EPI infusion (P < 0.001). RONS was 2.5 times greater in the EPI group than in the control group (P < 0.05). In conclusion, a significant deterioration in cardiac function was observed after EPI perfusion and was associated with cellular injury and the generation of myocardial RONS. Further investigations are now needed to determine whether new cardioprotective agents targeting oxidative stress may reduce the incidence of anthracycline-induced cardiotoxicity.
Delemasure
Stéphanie
S
Laboratory of Cardiovascular Experimental Pharmacology and Physiopathology, IFR n 100, Faculties of Medicine and Pharmacy, University of Burgundy, Dijon, France. stephanie.delemasure@gmail.com
Sicard
Pierre
P
Lauzier
Benjamin
B
Moreau
Daniel
D
Vergely
Catherine
C
Rochette
Luc
L
D000704:Analysis of Variance; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D015251:Epirubicin / Q000008:administration & dosage / Q000494:pharmacology*; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010477:Perfusion / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D005609:Free Radicals; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D015251:Epirubicin; D007770:L-Lactate Dehydrogenase; D007545:Isoproterenol