Fenofibrate protects lipoproteins from lipid peroxidation: Synergistic interaction with α-tocopherol
| Autor: | Alan Edgar, Francois Bellamy, Dominique Maubrou-Sanchez, Evelyne Chaput |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
medicine.medical_specialty Very low-density lipoprotein Apolipoprotein B Normal diet Lipoproteins VLDL Biochemistry Rats Sprague-Dawley chemistry.chemical_compound Fenofibrate Internal medicine medicine Animals Vitamin E Lipoprotein oxidation Hypolipidemic Agents Bezafibrate biology Cholesterol Organic Chemistry Drug Synergism Cell Biology Rats Lipoproteins LDL Endocrinology chemistry biology.protein lipids (amino acids peptides and proteins) Lipid Peroxidation Gemfibrozil Lipoprotein medicine.drug |
| Zdroj: | Lipids. 34:497-502 |
| ISSN: | 1558-9307 0024-4201 |
| DOI: | 10.1007/s11745-999-0390-8 |
| Popis: | 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 alpha-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 alpha-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 alpha-tocopherol. Combined VLDL (very low density lipoproteins) and LDL (low density lipoproteins) isolated after fenofibrate treatment were more resistant to copper-mediated 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 alpha-tocopherol alone at the selected dose had no significant effect on lag time, while the propagation rate was slightly decreased. Coadministration of fenofibrate with alpha-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 alpha-tocopherol was significantly more effective in modifying lipoprotein oxidation parameters than what was observed with alpha-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 alpha-tocopherol. |
| Databáze: | OpenAIRE |
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