Atherosclerosis 144 (1999) 69 – 72 Oxidizability of low density lipoprotein and total antioxidative capacity of plasma are differently altered during induction and regression of hypercholesterolemia in rabbits W. Schneider a , P. Dalferth b , O. Kelber a , G. Friedemann b , R. Haasis c , H. Heinle b, * a Steigerwald Arzneimittel GmbH, Darmstadt, Germany b Physiological Institute, Uniersity of Tu ¨bingen, Gmelinstr, 5, 72076 Tu ¨bingen, Germany c Clinics of Internal Medicine III, Uniersity of Tu ¨bingen, Tu ¨bingen, Germany Received 11 February 1998; accepted 4 September 1998 Abstract Oxidizability of isolated low density lipoprotein (LDL) and total antioxidative capacity of plasma were measured in rabbits fed for 6 weeks a cholesterol-rich diet and for further 34 weeks a normal diet. Whereas the time to induce copper ion-mediated lipid peroxidation in LDL was prolonged during hypercholesterolemia, total antioxidative capacity as determined by a radical-trapping assay was increased at 6 weeks, but decreased during the time when the plasma cholesterol levels declined slowly to normal. Since aortic plaque progression was continued also during the first 15 weeks of normal diet, increased atherogenicity of hypercholes- terolemia might be better reflected by the antioxidant capacity of plasma rather than by oxidation of isolated LDL. © 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Antioxidative capacity of plasma; Hypercholesterolemia; Intimal plaque progression; Oxidation of isolated LDL; Regression 1. Introduction Oxidation of low density lipoprotein (LDL) and its chemical modification within the arterial intima seem to represent crucial primary steps in atherogenesis [1 – 3]. Among other effects, intimal accumulation of mono- cytes, macrophage-foam cell formation, induction of endothelial dysfunction, intimal proliferation of smooth muscle cells as well as development of atheromatous lesions are supposed actions of modified LDL, or are at least supported by its activity [4 – 6]. Although oxidized and modified LDL could be demonstrated in human and experimentally induced atherosclerotic plaques [7 – 9], little is known about the reaction conditions and the molecular mechanisms involved in the arterial vessel wall in vivo. In vitro, however, there exist several established methods by which oxidation and modifica- tion of isolated LDL can be studied. Catalysis of oxidation by copper ions as introduced by Esterbauer [2] is generally accepted and widely used for the deter- mination of oxidizability of LDL. In this test, the lag time of dien-formation or production of thiobarbituric acid-reactive substances (TBARS) is measured, which is often used for characterization of the atherogenicity of LDL or of the therapeutic usefulness of antioxidants [10,11]. Yet, the question is whether the oxidation under these conditions reflects the situation in the vessel wall. Since one can assume that antioxidants present in blood plasma are in equilibrium with the extracellular fluid of the vessel wall, the determination of the antiox- idative resistance of plasma or serum might provide more information. This parameter can be measured * Corresponding author. Tel.: +49-7071-297-3420; fax: +49- 7071-29-3073. E-mail address: helmut.heinle@uni-tuebingen.de (H. Heinle) 0021-9150/99/$ - see front matter © 1999 Elsevier Science Ireland Ltd. All rights reserved. PII:S0021-9150(99)00047-7