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

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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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A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302
Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays
Mosmann, T. (1983) · Journal of Immunological Methods · doi:10.1016/0022-1759(83)90303-4 · Cited by 56,104
Antioxidant activity applying an improved ABTS radical cation decolorization assay
Re, R., Pellegrini, N., Proteggente, A. R., Pannala, A. S., Yang, M. H., & Rice-Evans, C. A. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(98)00315-3 · Cited by 26,986
A simple technique for quantitation of low levels of DNA damage in individual cells
Singh, N. P., McCoy, M. T., Tice, R. R., & Schneider, E. L. (1988) · Experimental Cell Research · doi:10.1016/0014-4827(88)90265-0 · Cited by 10,828
The Effects of Plant Flavonoids on Mammalian Cells:Implications for Inflammation, Heart Disease, and Cancer
Middleton, E., Kandaswami, C., & Theoharides, T. C. (2000) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01472-8 · Cited by 4,882
Dietary Intake and Bioavailability of Polyphenols
Scalbert, A., & Williamson, G. (2000) · The Journal of Nutrition · doi:10.1093/jn/130.8.2073s · Cited by 3,658
Review of the biology of quercetin and related bioflavonoids
Formica, J. V., & Regelson, W. (1995) · Food and Chemical Toxicology · doi:10.1016/0278-6915(95)00077-1 · Cited by 1,779
Flavonoid intake and risk of chronic diseases
Knekt, P., Kumpulainen, J. T., Järvinen, R., Rissanen, H. A., Heliövaara, M., Reunanen, A., Hakulinen, T., & Aromaa, A. (2002) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/76.3.560 · Cited by 1,765
Interactions of Flavonoids with Iron and Copper Ions: A Mechanism for their Antioxidant Activity
Mira, L., Fernandez, M. T., Santos, M., Rocha, R., Florêncio, M. H., & Jennings, K. R. (2002) · Free Radical Research · doi:10.1080/1071576021000016463 · Cited by 1,055
A comparative evaluation of thiobarbituric acid methods for the determination of malondialdehyde in biological materials
Draper, H. H., Squires, E. J., Mahmoodi, H., Wu, J., Agarwal, S., & Hadley, M. (1993) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(93)90035-s · Cited by 916

Show all 49 references

Research works printed but not linked: 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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(2008) · PubMed Central · Cited by 46
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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: Wätjen, Wim
Chovolou, Yvonni
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: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 6547 d)
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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Low Concentrations of Flavonoids Are Protective in Rat H4IIE Cells Whereas High Concentrations Cause DNA Damage and Apoptosis,

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