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The quercetin paradox

Journal Article · · Toxicology and Applied Pharmacology
 [1];  [2];  [2];  [2];  [3];  [1]
  1. Department of Pharmacology and Toxicology, Faculty of Medicine, University of Maastricht, PO Box 616, 6200 MD Maastricht (Netherlands)
  2. Institut fuer Umweltmedizinische Forschung (IUF), Heinrich-Heine Universitaet Duesseldorf, Auf 'm Hennekamp 50, 40255 Duesseldorf (Germany)
  3. Department of Biochemistry, Faculty of Health Sciences, University of Maastricht, PO Box 616, 6200 MD Maastricht (Netherlands)

Free radical scavenging antioxidants, such as quercetin, are chemically converted into oxidation products when they protect against free radicals. The main oxidation product of quercetin, however, displays a high reactivity towards thiols, which can lead to the loss of protein function. The quercetin paradox is that in the process of offering protection, quercetin is converted into a potential toxic product. In the present study, this paradox is evaluated using rat lung epithelial (RLE) cells. It was found that quercetin efficiently protects against H{sub 2}O{sub 2}-induced DNA damage in RLE cells, but this damage is swapped for a reduction in GSH level, an increase in LDH leakage as well as an increase of the cytosolic free calcium concentration. To our knowledge, this is the first study that indicates that the quercetin paradox, i.e. the exchange of damage caused by quercetin and its metabolites, also occurs in living lung cells. Following depletion of GSH in the cells by BSO pre-treatment, this quercetin paradox becomes more pronounced, confirming that the formation of thiol reactive quercetin metabolites is involved in the quercetin paradox. The quercetin paradox in living cells implies that the anti-oxidant directs oxidative damage selectively to thiol arylation. Apparently, the potential toxicity of metabolites formed during the actual antioxidant activity of free radical scavengers should be considered in antioxidant supplementation.

OSTI ID:
20976975
Journal Information:
Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 222; ISSN TXAPA9; ISSN 0041-008X
Country of Publication:
United States
Language:
English

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