Cardiovascular Toxicology

, Volume 12, Issue 2, pp 158–165 | Cite as

Grape Seed and Skin Extract Protects Against Acute Chemotherapy Toxicity induced by Doxorubicin in Rat Heart

  • Meherzia MokniEmail author
  • Sonia Hamlaoui-Guesmi
  • Mohamed Amri
  • Lamjed Marzouki
  • Ferid Limam
  • Ezzedine Aouani


Doxorubicin (Dox), an antitumor anthracycline antibiotic, plays a key role in the treatment of many neoplastic diseases. However, its chronic administration induces cardiomyopathy. Increased oxidative stress is a major factor implicated in Dox-induced cardiotoxicity. We hypothesized that a pre-treatment with grape seed and skin extract (GSE), commonly used as an antioxidant agent, may alleviate this cardiotoxicity. Rats were treated with GSE (500 mg/kg bw) by intraperitoneal injection during 8 days. On the 4th day, rats were administered a single dose of Dox (20 mg/kg). At the end of the treatment, their hearts were Langendorff-perfused, subjected to ischemia/reperfusion (I/R) injury, and left ventricular functions as heart rate and developed pressure measured. Hearts were also used to determine free iron, H2O2, Ca2+, lipoperoxidation, carbonylation and antioxidant enzymes such as superoxide dismutase (SOD), catalase and peroxidase. Doxorubicin drastically affected heart activity as evidenced after I/R experiments. This effect was associated with an increase in heart free iron and a decrease in Ca2+ concentrations. This effect may have contributed to oxidative stress as assessed by high lipoperoxidation and carbonylation level. GSE counteracted Dox-induced disturbances of hemodynamic parameters, alleviated oxidative stress as assessed by normalized iron and Ca2+ levels and increased SOD activity especially the Mn isoform.


Dox GSE Heart activity Ca2+ levels SOD CAT POD 



We gratefully acknowledge the financial support of the Tunisian Ministry of High Education, Scientific Research and Technology.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Meherzia Mokni
    • 1
    Email author
  • Sonia Hamlaoui-Guesmi
    • 1
  • Mohamed Amri
    • 1
  • Lamjed Marzouki
    • 1
  • Ferid Limam
    • 2
  • Ezzedine Aouani
    • 2
  1. 1.Laboratoire de Neurophysiologie Fonctionnelle et Pathologies, Département des Sciences Biologiques, Faculté des Sciences de TunisCampus Universitaire El Manar IITunisTunisia
  2. 2.Laboratoire des Substances Bioactives, Centre de BiotechnologieTechnopole Borj-CedriaHammam-LifTunisia

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