QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wätjen, W. Articles by Kahl, R. Search for Related Content PubMed PubMed Citation Articles by Wätjen, W. Articles by Kahl, R.

---

Nutrient Interactions and Toxicity

Low Concentrations of Flavonoids Are Protective in Rat H4IIE Cells Whereas High Concentrations Cause DNA Damage and Apoptosis^1,2

Institute of Toxicology, Heinrich-Heine-University, 40001 Düsseldorf, Germany; and ^* Institute of Pharmaceutical Biology, Heinrich-Heine-University, 40225 Düsseldorf, Germany

³To whom correspondence should be addressed. E-mail: wim.waetjen{at}uni-duesseldorf.de.

Dietary flavonoids possess a wide spectrum of biochemical and pharmacological actions and are assumed to protect human health. These actions, however, can be antagonistic, and some health claims are mutually exclusive. The antiapoptotic actions of flavonoids may protect against neurodegenerative diseases, whereas their proapoptotic actions could be used for cancer chemotherapy. This study was undertaken to determine whether a cytoprotective dose range of flavonoids could be differentiated from a cytotoxic dose range. Seven structurally related flavonoids were tested for their ability to protect H4IIE rat hepatoma cells against H₂O₂-induced damage on the one hand and to induce cellular damage on their own on the other hand. All flavonoids proved to be good antioxidants in a cell-free assay. However, their pharmacologic activity did not correlate with in vitro antioxidant potential but rather with cellular uptake. For quercetin and fisetin, which were readily taken up into the cells, protective effects against H₂O₂-induced cytotoxicity, DNA strand breaks, and apoptosis were detected at concentrations as low as 10–25 µmol/L. On the other hand, these flavonoids induced cytotoxicity, DNA strand breaks, oligonucleosomal DNA fragmentation, and caspase activation at concentrations between 50 and 250 µmol/L. Published data on quercetin pharmacokinetics in humans suggest that a dietary supplement of 1–2 g of quercetin may result in plasma concentrations between 10 and 50 µmol/L. Our data suggest that cytoprotective concentrations of some flavonoids are lower by a factor of 5–10 than their DNA-damaging and proapoptotic concentrations.

KEY WORDS: • apoptosis • comet assay • fisetin • quercetin • uptake

This article has been cited by other articles:

				W. Chen, X. Wang, J. Zhuang, L. Zhang, and Y. Lin Induction of death receptor 5 and suppression of survivin contribute to sensitization of TRAIL-induced cytotoxicity by quercetin in non-small cell lung cancer cells Carcinogenesis, October 1, 2007; 28(10): 2114 - 2121. [Abstract] [Full Text] [PDF]

				A. B. Granado-Serrano, M. A. Martin, L. Bravo, L. Goya, and S. Ramos Quercetin Induces Apoptosis via Caspase Activation, Regulation of Bcl-2, and Inhibition of PI-3-Kinase/Akt and ERK Pathways in a Human Hepatoma Cell Line (HepG2) J. Nutr., November 1, 2006; 136(11): 2715 - 2721. [Abstract] [Full Text] [PDF]