title: The effects of N-acetylcysteine on cisplatin-induced changes of cardiodynamic parameters within coronary autoregulation range in isolated rat hearts.
abstract: The aim of this study was to evaluate the effects of chronic NAC administration along with cisplatin on cisplatin-induced cardiotoxicity by means of coronary flow (CF), cardiodynamic parameters, oxidative stress markers and morphological changes in isolated rat heart. Isolated hearts of Wistar albino rats (divided into four groups: control, cisplatin, NAC and cisplatin+NAC group) were perfused according to Langendorff technique at constant coronary perfusion pressure starting at 50 and gradually increased to 65, 80, 95 and 110 cm H2O to evaluate cardiodynamic parameters within autoregulation range. Samples of coronary venous effluent (CVE) were collected for determination of CF and biochemical assays, and heart tissue samples for biochemical assays and histopathological examination. Cisplatin treatment decreased CF and heart rate, and increased left ventricular systolic pressure and maximum left ventricular pressure development rate. Cisplatin increased H2O2 and TBARS, but decreased NO2(-) levels in CVE. In tissue samples, cisplatin reduced pathological alterations in myocardium and coronary vessels, with no changes in the amount of total glutathione, as well as in activity of glutathione peroxidase and glutathione reductase. NAC coadministration, by reducing oxidative damage, attenuated cisplatin-induced changes of cardiodynamic and oxidative stress parameters, as well as morphological changes in myocardium and coronary vasculature.
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Serbia. Electronic address: grosic@medf.kg.ac.rs.
authors.forename: Gvozden
authors.initials: G
authors.lastname: Rosic
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Serbia. Electronic address: dragica984@gmail.com.
authors.forename: Dragica
authors.initials: D
authors.lastname: Selakovic
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Serbia. Electronic address: jovana_joksimovic@yahoo.com.
authors.forename: Jovana
authors.initials: J
authors.lastname: Joksimovic
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Serbia. Electronic address: ivan_srejovic@hotmail.com.
authors.forename: Ivan
authors.initials: I
authors.lastname: Srejovic
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Serbia. Electronic address: vladimirziv@gmail.com.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Zivkovic
authors.affiliation: Department of Physiology, Institute for Biological Research, University of Belgrade, Serbia. Electronic address: nikola.tatalovic@ibiss.bg.ac.rs.
authors.forename: Nikola
authors.initials: N
authors.lastname: Tatalović
authors.affiliation: Department of Physiology, Institute for Biological Research, University of Belgrade, Serbia. Electronic address: zoranaor@ibiss.bg.ac.rs.
authors.forename: Zorana
authors.initials: Z
authors.lastname: Orescanin-Dusic
authors.affiliation: Department of Pathology, Faculty of Medical Sciences, University of Kragujevac, Serbia. Electronic address: smitrovic@medf.kg.ac.rs.
authors.forename: Slobodanka
authors.initials: S
authors.lastname: Mitrovic
authors.affiliation: Department of Pathology, Faculty of Medical Sciences, University of Kragujevac, Serbia. Electronic address: lena.ilic@gmail.com.
authors.forename: Milena
authors.initials: M
authors.lastname: Ilic
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Serbia. Electronic address: drvladakgbg@yahoo.com.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Jakovljevic
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002945:Cisplatin; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D019610:Cytoprotection; D004195:Disease Models, Animal; D006331:Heart Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects; D006706:Homeostasis; D000067268:Isolated Heart Preparation; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D002316:Cardiotonic Agents; D002945:Cisplatin; D000111:Acetylcysteine
keywords: Cisplatin; Coronary autoregulation; Histology; Isolated rat heart; N-acetylcysteine; Oxidative stress