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Cited by 240Phytochemicals and Antioxidant ActivitiesFlavonoids in Medical ResearchBioactive Compounds and Antitumor Agents

The DOI matches its Crossref record; 48 of the 49 references it cites were found in a registry or an index.

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

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Wätjen, Wim, Michels, Gudrun, Steffan, Bärbel, Niering, Petra, Chovolou, Yvonni, Kampkötter, Andreas, Tran-Thi, Quynh-Hoa, Proksch, Peter, Kahl, Regine·2005·The Journal of Nutrition
DOI 10.1093/jn/135.3.525
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Abstract

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 H(2)O(2)-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 H(2)O(2)-induced cytotoxicity, DNA strand breaks, and apoptosis were detected at concentrations as low as 10-25 micromol/L. On the other hand, these flavonoids induced cytotoxicity, DNA strand breaks, oligonucleosomal DNA fragmentation, and caspase activation at concentrations between 50 and 250 micromol/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 micromol/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.

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  1. Wittig, 2000, Beta-glucuronidase activity in human endothelial tissues in an in-vitro model using primary monolayer cultures of human umbilical vein endothelial cells (HUVEC), Polyphenols Commun., 2, 459

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Metadata

Authors
Wätjen, W., Michels, G., Steffan, B., Niering, P., Chovolou, Y., Kampkötter, A., Tran-Thi, Q.-H., Proksch, P., & Kahl, R.
Affiliations
Heinrich Heine University Düsseldorf (DE)
Corresponding author
Wätjen, Wim
ORCID
Venue
The Journal of Nutrition
Publisher
Elsevier BV
Published
2005-03
Volume
135
Issue
3
Pages
525-531
ISSN
0022-3166 (ISSN-L)
DOI
10.1093/jn/135.3.525
OpenAlex
W1912855510
Cited by
240
References
49
Citations by year
2026: 6 · 2025: 7 · 2024: 7 · 2023: 6 · 2022: 14 · 2021: 12 · 2020: 9 · 2019: 14 · 2018: 8 · 2017: 17 · 2016: 18 · 2015: 8 · 2014: 26 · 2013: 10 · 2012: 15
FWCI
5.76
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Nutrition (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
  • Health Sciences › Medicine › Pharmacology (medical) › Flavonoids in Medical Research
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
Keywords
flavonoids, quercetin, fisetin, H4IIE cells, hydrogen peroxide-induced cytotoxicity, DNA strand breaks, apoptosis, caspase activation, oligonucleosomal DNA fragmentation, cellular uptake, antioxidant activity, dose-dependent effects, cytoprotection, hepatoprotection, dietary flavonoids
MeSH terms
Animals, Cell Line, Cell-Free System, DNA Damage, Flavonoids, Carcinoma, Hepatocellular, Hydrogen Peroxide, Kinetics, Liver Neoplasms, Apoptosis, Cell Line, Tumor, Rats

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