title: Doxorubicin-induced behavioral disturbances in rats: protective effect of melatonin and captopril.
abstract: OBJECTIVE
  Doxorubicin is a recognized chemotherapeutic agent widely employed in human malignancies. The limiting factor of its use is a number of side effects. The aim of this work was to show, whether administration of doxorubicin could induce behavioral disturbances in rats, and whether angiotensin-converting enzyme inhibitor captopril or melatonin can modify these potential alterations.
  
  
  METHODS
  Four groups of 3-month-old Wistar rats (twelve per group) were treated for 4 weeks: control (placebo-treated), doxorubicin (DOX) (5mg/kg i.v. in a single intravenous dose), DOX rats treated with either melatonin (10mg/kg/24h) or captopril (100mg/kg/24h). Systolic blood pressure (SBP) and the level of oxidative stress were investigated and behavioral tests of anxiety-open field test (OF), elevated plus maze (EPM) and light-dark box (LDB) were accomplished.
  
  
  RESULTS
  Doxorubicin increased significantly systolic blood pressure and parameters of oxidative stress. Moreover, doxorubicin enhanced the level of anxiety in the tests of OF, EPM, and LDB. Captopril and melatonin prevented the blood pressure rise and the enhancement of oxidative load. Importantly, both substances reduced the parameters of anxiety.
  
  
  CONCLUSIONS
  Chronic administration of captopril or melatonin has shown anxiolytic effect in the model of doxorubicin-induced anxiety. It does not seem unreasonable to suppose that this protective effect of captopril or melatonin against anxiety development might have been related to the antioxidative effects of both substances.
authors.affiliation: Department of Pathophysiology, School of Medicine, Comenius University, Bratislava, Slovak Republic.
authors.forename: S
authors.initials: S
authors.lastname: Aziriova
authors.affiliation: Department of Pathophysiology, School of Medicine, Comenius University, Bratislava, Slovak Republic.
authors.forename: K
authors.initials: K
authors.lastname: Repova Bednarova
authors.affiliation: Department of Pathophysiology, School of Medicine, Comenius University, Bratislava, Slovak Republic.
authors.forename: K
authors.initials: K
authors.lastname: Krajcirovicova
authors.affiliation: Department of Pathophysiology, School of Medicine, Comenius University, Bratislava, Slovak Republic.
authors.forename: J
authors.initials: J
authors.lastname: Hrenak
authors.affiliation: Department of Pathophysiology, School of Medicine, Comenius University, Bratislava, Slovak Republic.
authors.forename: R
authors.initials: R
authors.lastname: Rajkovicova
authors.affiliation: Department of Pathophysiology, School of Medicine, Comenius University, Bratislava, Slovak Republic.
authors.forename: K
authors.initials: K
authors.lastname: Arendasova
authors.affiliation: Institute of Molecular Biomedicine, School of Medicine, Comenius University, Bratislava, Slovak Republic.
authors.forename: N
authors.initials: N
authors.lastname: Kamodyova
authors.affiliation: Department of Pathophysiology, School of Medicine, Comenius University, Bratislava, Slovak Republic; Institute of Molecular Biomedicine, School of Medicine, Comenius University, Bratislava, Slovak Republic.
authors.forename: P
authors.initials: P
authors.lastname: Celec
authors.affiliation: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: S
authors.initials: S
authors.lastname: Zorad
authors.affiliation: Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Adamcova
authors.affiliation: Department of Pathophysiology, School of Medicine, Comenius University, Bratislava, Slovak Republic.
authors.forename: L
authors.initials: L
authors.lastname: Paulis
authors.affiliation: Department of Pathophysiology, School of Medicine, Comenius University, Bratislava, Slovak Republic; Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovak Republic; 3rd Clinic of Medicine, School of Medicine, Comenius University, Bratislava, Slovak Republic; Center of Excellence, NOREG, Slovak Republic. Electronic address: fedor.simko@fmed.uniba.sk.
authors.forename: F
authors.initials: F
authors.lastname: Simko
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D004336:Drug Antagonism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D004317:Doxorubicin; D002216:Captopril; D008550:Melatonin
keywords: Anxiety; Captopril; Doxorubicin; Melatonin; Oxidative stress; Protection