Modulation of doxorubicin-induced oxidative stress by a grape (Vitis vinifera L.) seed extract in normal and tumor cells

J Med Food. 2012 Jul;15(7):639-45. doi: 10.1089/jmf.2011.0291. Epub 2012 Apr 20.


The major limitation of Doxorubicin (Dox) clinical use is the development of chronic and acute toxic side effects induced through the generation of reactive oxygen species. The present work was designated to investigate in vitro effects of a red grape-seed hydroethanolic extract Burgund Mare (BM), in associated administration with Dox (30 min before drug administration) in normal (Hfl-1) and tumor cell lines (HepG2 and Mls). The BM concentrations administered were below the level of the extract cytotoxiciy threshold (40 μg gallic acid [GA] Eq/mL; 37.5, 25.0, and 12.5 μg GA Eq/mL). The antioxidant capacity of the BM extract was assessed by measuring the acute toxicity at 24 h, lipid peroxides (LP), and protein oxidation. In normal cells, the product statistically decreased cytotoxicity and markedly inhibited LP and protein carbonyl (PC) formation, in a dose-dependent relationship. On contrary, in tumor cells, such treatment resulted in a reversed effect, cell death, malondialdehyde, and PC contents increasing with BM dose enhancement. BM extract treatment prior to subsequent administration of Dox afforded a differential protection against Dox-negative toxic side effects in normal cells without weakening (even enhancing) Dox's antitumor activity.

MeSH terms

  • Antibiotics, Antineoplastic* / adverse effects
  • Antibiotics, Antineoplastic* / therapeutic use
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Cell Death / drug effects
  • Cell Line
  • Dose-Response Relationship, Drug
  • Doxorubicin* / adverse effects
  • Doxorubicin* / therapeutic use
  • Drug Synergism
  • Hep G2 Cells
  • Humans
  • Lipid Peroxidation / drug effects
  • Malondialdehyde / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Oxidants / pharmacology
  • Oxidants / therapeutic use
  • Oxidative Stress / drug effects*
  • Phytotherapy
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Protein Carbonylation / drug effects
  • Seeds
  • Vitis*


  • Antibiotics, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • Oxidants
  • Plant Extracts
  • Malondialdehyde
  • Doxorubicin