Cytotoxicity induced by grape seed proanthocyanidins: Role of nitric oxide

Z. H. Shao, C. W. Hsu, W. T. Chang, G. B. Waypa, J. Li, D. Li, C. Q. Li, T. Anderson, Y. Qin, P. T. Schumacker, L. B. Backer, T. L. Vanden Hoek*

*Corresponding author for this work

Research output: Contribution to journalArticle

34 Scopus citations


Grape seed proanthocyanidin extract (GPSE) at high doses has been shown to exhibit cytotoxicity that is associated with increased apoptotic cell death. Nitric oxide (NO), being a regulator of apoptosis, can be increased in production by the administration of GSPE. In a chick cardiomyocyte study, we demonstrated that high-dose (500 μg/ml) GSPE produces a significantly high level of NO that contributes to increased apoptotic cell death detected by propidium iodide and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. It is also associated with the depletion of intracellular glutathione (GSH), probably due to increased consumption by NO with the formation of S-nitrosoglutathione. Co-treatment with L-NAME, a NO synthase inhibitor, results in reduction of NO and apoptotic cell death. The decline in reduced GSH/oxidized GSH (GSSG) ratio is also reversed. N-Acetylcysteine, a thiol compound that reacts directly with NO, can reduce the increased NO generation and reverse the decreased GSH/GSSG ratio, thereby attenuating the cytotoxicity induced by high-dose GSPE. Taken together, these results suggest that endogenous NO synthase (NOS) activation and excessive NO production play a key role in the pathogenesis of high-dose GSPE-induced cytotoxicity.

Original languageEnglish (US)
Pages (from-to)149-158
Number of pages10
JournalCell Biology and Toxicology
Issue number3
StatePublished - May 1 2006


  • Cardiomyocyte
  • Grape seed proanthocyanidins
  • Nitric-oxide synthase
  • Nitricoxide
  • Oxidant stress

ASJC Scopus subject areas

  • Toxicology
  • Cell Biology
  • Health, Toxicology and Mutagenesis

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    Shao, Z. H., Hsu, C. W., Chang, W. T., Waypa, G. B., Li, J., Li, D., Li, C. Q., Anderson, T., Qin, Y., Schumacker, P. T., Backer, L. B., & Vanden Hoek, T. L. (2006). Cytotoxicity induced by grape seed proanthocyanidins: Role of nitric oxide. Cell Biology and Toxicology, 22(3), 149-158.