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Beneficial role of aminoguanidine on acute cardiomyopathy related to doxorubicin-treatment

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Abstract

Doxorubicin (DOX) is a broad-spectrum anthracycline antibiotic that has cardiotoxicity as a major side effect. One mechanism of this toxicity is believed to involve the reactive oxygen radical species (ROS); these agents likely account for the pathophysiology of DOX-induced cardiomyopathy. Aminoguanidine (AG) is an effective antioxidant and free radical scavenger which has long been known to protect against ROS formation. We investigated the effects of AG on DOX-induced changes in thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) content. The rats were divided into four groups:1) Control; 2) DOX group; injected intraperitoneally (i.p.) with DOX 20 mg/kg in a single dose 3) AG-treated group; injected i.p. in single dose of 20 mg/kg DOX plus 100 mg/kg AG 1 h before the DOX for 3 days, 4) AG group; injected i.p. with AG 100 mg/kg for 3 days. DOX administration to control rats increased TBARS and decreased GSH levels. AG administration before DOX injection caused significant decrease in TBARS and increase in GSH levels in the heart tissue when compared with DOX only. Morphological changes, including severe myocardial fibrosis and inflammatory cell infiltration were clearly observed in the DOX-treated heart. AG reversed the DOX-induced heart damage. Therefore AG could protect the heart tissue against free radical injury. The application of AG during cancer chemotherapy may attenuate tissue damage and improve the therapeutic index of DOX.

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Abbreviations

DOX:

doxorubicin

AG:

aminoguanidine

ROS:

reactive oxygen radical species

GSH:

reduced glutathione

TBARS:

thiobarbituric acid reactive substances

NO:

nitric oxide

iNOS:

inducible nitric oxide synthase

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Authors and Affiliations

  1. Department of Biology, Faculty of Art and Science, Kafkas University, Kars, Turkey

    Yilmaz Cigremis

  2. Department of Pharmacology, Faculty of Medicine, Inonu University, Malatya, Turkey

    Hakan Parlakpinar MD & Ahmet Acet

  3. Department of Physiology, Faculty of Medicine, Inonu University, Malatya, Turkey

    Alaadin Polat

  4. Republic of Turkey Prime Ministry, Under Secretariat of Customs Directorate General of Customs, Ankara, Turkey

    Cemil Colak

  5. Department of Histology, Faculty of Medicine, Inonu University, Malatya, Ankara, Turkey

    Feral Ozturk

  6. Department of Pharmacology, Faculty of Medicine, Firat University, Elazig, Turkey

    Engin Sahna

  7. Department of Cardiology, Faculty of Medicine, Inonu University, Malatya, Turkey

    Necip Ermis

  8. Department of Pharmacology, Faculty of Medicine, Inonu University, 44280, Malatya, Turkey

    Hakan Parlakpinar MD

Authors
  1. Yilmaz Cigremis
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  2. Hakan Parlakpinar MD
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  3. Alaadin Polat
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  4. Cemil Colak
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  5. Feral Ozturk
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  6. Engin Sahna
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  8. Ahmet Acet
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Correspondence to Hakan Parlakpinar MD.

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Cigremis, Y., Parlakpinar, H., Polat, A. et al. Beneficial role of aminoguanidine on acute cardiomyopathy related to doxorubicin-treatment. Mol Cell Biochem 285, 149–154 (2006). https://doi.org/10.1007/s11010-005-9072-8

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  • DOI: https://doi.org/10.1007/s11010-005-9072-8

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