Toxicology Letters 151 (2004) 105–111 The thiol reactivity of the oxidation product of 3,5,7-trihydroxy-4H-chromen-4-one containing flavonoids G. Michels a , G.R.M.M. Haenen b , W. Wätjen a , S. Rietjens b , A. Bast b,∗ a Institute of Toxicology, University of Düsseldorf, P.O. Box 101007, 4001 Düsseldorf, Germany b Department of Pharmacology and Toxicology, University of Maastricht, Postbus 616, Maastricht, NL-6200, The Netherlands Received 5 January 2004; received in revised form 6 January 2004; accepted 6 January 2004 Dedicated to the late Christian Hodel Available online 17 April 2004 Abstract Flavonoids are assumed to have beneficial effects due to their antioxidant properties. The catechol moiety present in numerous flavonoids is oxidized during the antioxidative reaction yielding a quinone. Quinones are toxic due to their ability to react, e.g. with thiol groups. The 3,5,7-trihydroxy-4H-chromen-4-one group is another antioxidant pharmacophor in certain flavonoids. During the antioxidative reaction this group is also oxidized. The aim of the present study is to determine the thiol reactivity of this oxidized group. Galangin is a flavonoid that only contains the 3,5,7-trihydroxy-4H-chromen-4-one group as the antioxidant pharmacophor. Incubation of galangin with horseradish peroxidase/H 2 O 2 leads to an oxidation product which after addition of glutathione is instantaneously converted to an adduct. Based on these results it is expected that—similar to the catechol containing antioxidants—the 3,5,7-trihydroxy-4H-chromen-4-one containing antioxidants shift the damage provoked by oxidative stress from lipid peroxidation to thiol arylation. This should be considered in application of these types of antioxidants. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Flavonoids; Galangin; Reactive oxygen species; Glutathione adduct; Quinones; Quinone formation 1. Introduction More than 6000 flavonoids are known as polyphe- nolic components of vegetables and fruits. The an- Abbreviations: HRP, horseradish peroxidase; DAD, diode ar- ray detector; GSH, glutathione; GSTP1-1, GSH transferase P1-1; DMEM, Dulbecco’s modified Eagles’s medium; H 2 O 2 , hydrogen peroxide; HPLC, high-performance liquid chromatography ∗ Corresponding author. Tel: +31-43-3881418; fax: +31-43-3881419. E-mail address: a.bast@farmaco.unimaas.nl (A. Bast). tioxidative effects of flavonoids are claimed to provide protection against diseases like cancer, coronary heart disease or neurodegenerative diseases. Flavonoids can contain two different pharmacophors, a catechol structure and a 3,5,7-trihydroxy-4H-chromen-4-one group. During the antioxidative action, the antioxidant is converted into an oxidized product. In general, or- tho and para diols are easily oxidized to quinones, as seen with flavonoids with a catechol structure in the B-ring, e.g. quercetin, luteolin, naringenin and api- genin (Galati et al., 1999, 2001). Subsequently, glu- 0378-4274/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.toxlet.2004.01.017