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Mechanisms of beneficial effects of probucol in adriamycin cardiomyopathy

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Stress Adaptation, Prophylaxis and Treatment

Part of the book series: Molecular and Cellular Biochemistry ((DMCB,volume 32))

Abstract

Probucol, a lipid-lowering drug, has been shown to offer protection against adriamycin-induced cardiomyopathy. In order to define the mechanism of this protection, we examined changes in antioxidants and lipid peroxidation in hearts as well as lipids in hearts and plasma from rats treated with either adriamycin or adriamycin and probucol with appropriate controls. Any potential free radical quenching as well as growth inhibitory effects of probucol were also examined using Chinese hamster ovary (CHO) cells in culture. In animal model, adriamycin caused a significant depression in glutathione peroxidase and increased plasma and cardiac lipids as well as lipid peroxidation. Probucol treatment modulated adriamycin-induced cardiomyopathy changes and increased glutathione peroxidase and superoxide dismutase activities. In the presence of adriamycin under hypoxic conditions, formation of adriamycin semiquinone radical was detected by ESR. The cell growth in these cultures was also inhibited by adriamycin in a dose-dependent manner. Probucol had no effect on adriamycin-induced growth inhibition as well as formation of semiquinone radicals. It is proposed that probucol protection against adriamycin cardiomyopathy is mediated by increased antioxidants and lipid-lowering without any effect on free radical production. ((Mol Cell Biochem 196: 43-49, 1999)

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Author information

Authors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Avenue, R3022, Winnipeg, MB, R2H 2A6, Canada

    Pawan K. Singal

  2. Institute of Cardiovascular Sciences, Department of Physiology and St. Boniface General Hospital Research Centre, Faculty of Medicine, Canada

    Natasha Iliskovic, Timao Li, Igor Danelisen & Pawan K. Singal

  3. Faculty of Pharmacy, University of Manitoba, Winnipeg, Canada

    Brian B. Hasinoff & Krisztina L. Malisza

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  1. Natasha Iliskovic
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  2. Brian B. Hasinoff
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  3. Krisztina L. Malisza
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  4. Timao Li
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  5. Igor Danelisen
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  6. Pawan K. Singal
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Editors and Affiliations

  1. Department of Surgery, University of Connecticut School of Medicine, Farmington, CT, 06030-1110, USA

    Dipak K. Das

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Iliskovic, N., Hasinoff, B.B., Malisza, K.L., Li, T., Danelisen, I., Singal, P.K. (1999). Mechanisms of beneficial effects of probucol in adriamycin cardiomyopathy. In: Das, D.K. (eds) Stress Adaptation, Prophylaxis and Treatment. Molecular and Cellular Biochemistry, vol 32. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5097-6_5

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  • DOI: https://doi.org/10.1007/978-1-4615-5097-6_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7319-3

  • Online ISBN: 978-1-4615-5097-6

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