S Aziriova1, K Repova Bednarova1, K Krajcirovicova1, J Hrenak1, R Rajkovicova1, K Arendasova1, N Kamodyova2, P Celec3, S Zorad4, M Adamcova5, L Paulis1, F Simko6. 1. Department of Pathophysiology, School of Medicine, Comenius University, Bratislava, Slovak Republic. 2. Institute of Molecular Biomedicine, School of Medicine, Comenius University, Bratislava, Slovak Republic. 3. Department of Pathophysiology, School of Medicine, Comenius University, Bratislava, Slovak Republic; Institute of Molecular Biomedicine, School of Medicine, Comenius University, Bratislava, Slovak Republic. 4. Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovak Republic. 5. Department of Physiology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic. 6. 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.
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. DESIGN AND 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. CONCLUSION: 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.
OBJECTIVE:Doxorubicin is a recognized chemotherapeutic agent widely employed in humanmalignancies. 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. DESIGN AND 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), DOXrats 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. CONCLUSION: 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.