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Doxorubicin-induced behavioral disturbances in rats: protective effect of melatonin and captopril
S. Aziriova, K. Repova Bednarova, K. Krajcirovicova, J. Hrenak, R. Rajkovicova, K. Arendasova, N. Kamodyova, P. Celec, S. Zorad, M. Adamcova, L. Paulis, F. Simko,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- antagonismus léků MeSH
- biologické markery metabolismus MeSH
- chování zvířat účinky léků MeSH
- doxorubicin farmakologie MeSH
- kaptopril farmakologie MeSH
- krevní tlak účinky léků MeSH
- krysa rodu rattus MeSH
- melatonin farmakologie MeSH
- oxidační stres účinky léků MeSH
- potkani Wistar MeSH
- protinádorová antibiotika farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
3rd Clinic of Medicine School of Medicine Comenius University Bratislava Slovak Republic
Center of Excellence NOREG Slovak Republic
Department of Pathophysiology School of Medicine Comenius University Bratislava Slovak Republic
Institute of Experimental Endocrinology Slovak Academy of Sciences Bratislava Slovak Republic
Institute of Molecular Biomedicine School of Medicine Comenius University Bratislava Slovak Republic
Citace poskytuje Crossref.org
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- $a 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.
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