Fenofibrate protects lipoproteins from lipid peroxidation: Synergistic interaction with α‐tocopherol

• Published in: Lipids 1999-05, Vol.34 (5), p.497-502
• Main Authors: Chaput, Evelyne, Maubrou‐Sanchez, Dominique, Bellamy, François D., Edgar, Alan D.
• Format: Article
• Language: English
• Subjects: Animals; Bezafibrate - pharmacology; Drug Synergism; Fenofibrate - pharmacology; Gemfibrozil - pharmacology; Hypolipidemic Agents - pharmacology; Lipid Peroxidation - drug effects; Lipoproteins, LDL - blood; Lipoproteins, VLDL - blood; Male; Rats; Rats, Sprague-Dawley; Vitamin E - pharmacology
• ISSN: 0024-4201; 1558-9307
• DOI: 10.1007/s11745-999-0390-8

One of the earliest steps of atherosclerotic plaque formation is an increase of circulating apolipoprotein B‐containing lipoproteins which, after infiltrating the subendothelial space, undergo oxidative modification. Fenofibrate is an effective cholesterol‐ and triglyceride‐lowering agent which has been shown to be beneficial in the treatment of atherosclerosis. Vitamin E, or α‐tocopherol, is a powerful antioxidant which has been shown in a variety of studies to prevent lipoprotein peroxidation. The purpose of the present study was to investigate the effect of fenofibrate treatment, either alone or in combination with α‐tocopherol, in reducing the susceptibility of lipoproteins to oxidative modification. Rats fed a normal diet were treated for up to 27 d with fenofibrate, either alone or in combination with equimolar doses of α‐tocopherol. Combined VLDL (very low density lipoproteins) and LDL (low density lipoproteins) isolated after fenofibrate treatment were more resistant to coppermediated oxidation, as assessed by conjugated diene formation. Lag time was prolonged up to 3.2‐fold, while the maximal rate of diene production was significantly decreased by up to 2.2‐fold. Treatment of rats with α‐tocopherol alone at the selected dose had no significant effect on lag time, while the propagation rate was slightly decreased. Coadministration of fenofibrate with α‐tocopherol prolonged the lag phase to a greater extent than fenofibrate alone, showing a synergistic interaction between the two compounds. Finally, the combination of fenofibrate and α‐tocopherol was significantly more effective in modifying lipoprotein oxidation parameters than what was observed with α‐tocopherol and bezafibrate or gemfibrozil. Thus, in addition to its well‐established effects on lipoprotein concentrations and atherogenic parameters, fenofibrate reduces the susceptibility of VLDL and LDL to oxidative modification and exerts its action synergistically with α‐tocopherol.