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Feb 28, 2008, 9:58:04 AM2/28/08

Radical-scavenging and iron-chelating properties of carvedilol, an
antihypertensive drug with antioxidative activity1

Karl Oettl, , a, Joachim Greilbergera, Klaus Zanggerb, Ernst
Haslingerb, Gilbert Reibneggera and Günther Jürgensa
a Institute for Medical Chemistry and Pregl Laboratory, Karl-Franzens-
University Graz, Harrachgasse 21/II, A-8010 Graz, Austria
b Institute of Pharmaceutical Chemistry, Karl-Franzens-University
Graz, Universitätsplatz 1, A-8010 Graz, Austria
Received 19 October 2000; accepted 2 February 2001 Available online 31
May 2001.

Abstract
Carvedilol, an antihypertensive agent, has been in clinical use for
several years. In addition to its function as a β-blocker, carvedilol
has been shown to act as an antioxidant. However, there is some
controversy as to how carvedilol achieves its antioxidative ability:
by radical scavenging or ion chelation? We therefore used a method of
radical generation independent of metal ions to investigate the
antioxidative properties of carvedilol. We showed that carvedilol
decreased low-density lipoprotein (LDL) oxidation induced by a peroxyl
radical-generating system [2,2′-azobis(2-
amidinopropane)hydrochloride]. Formation of thiobarbituric acid-
reactive substances, lipid hydroperoxides, and newly generated
epitopes on oxidised LDL was used to monitor LDL oxidation. We further
showed that carvedilol was consumed during reaction with peroxyl
radicals. However, carvedilol showed no reaction with nitrogen-
centered radicals (1,1-diphenyl-2-picrylhydrazyl and 2,2′-azino-di-[3-
ethylbenzthiazoline sulphonate]), which are often used in assays for
determining antioxidative properties. On the other hand, we found that
carvedilol acted as a chelator of ferric ions. Using mass spectrometry
and NMR spectroscopy, we observed complex formation with free and
acetylacetonate-complexed ferric ions. The binding constant with Fe3+
was in the range of 105 L/mol. From our data, we concluded that
carvedilol acts as both a metal chelator and a radical scavenger in
vitro. However, it is selective in reacting with different radicals
and is not an electron-donating radical scavenger as is α-tocopherol.
Therefore, taking into account the low physiological concentration,
the antioxidative properties reported earlier may not solely be
explained by its radical-scavenging activity.

Author Keywords: Carvedilol; Antioxidant; Free radicals; Radical
scavenger; Chelator; LDL

1 Abbreviations: ABTS, 2,2′-azino-di-[3-ethylbenzthiazoline
sulphonate]; AAPH, 2,2′-azobis(2-amidinopropane) hydrochloride; DPPH,
1,1-diphenyl-2-picrylhydrazyl; IgG, immunoglobulin G; LDL, low-density
lipoprotein; LPO, lipid peroxide; TBARS, thiobarbituric acid-reactive
substance; and apo B, apolipoprotein B.

Corresponding author. Tel.: +43-316-380-7544; fax: +43-316-380-9610;
email: karl....@kfunigraz.ac.at

Biochemical Pharmacology
Volume 62, Issue 2, 15 July 2001, Pages 241-248

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