DECREASED SUSCEPTIBILITY TO COPPER-INDUCED OXIDATION OF RAT-LIPOPROTEINS AFTER FIBRATE TREATMENT - INFLUENCE OF FATTY-ACID COMPOSITION

1 The effect of clofibrate (CFB), bezafibrate (BFB), and gemfibrozil ( GFB) on plasma lipoprotein (VLDL and LDL) concentration, composition a nd resistance to copper-induced oxidation has been studied in male Spr ague-Dawley rats after a 15 day treatment. 2 Plasma triglyceride level s were reduced by CFB (41%) and BFB (39%). This effect was related to a significant reduction (67% for CFB and 56% for BFB) in the amount of circulating VLDL-protein. 3 Plasma total cholesterol was reduced by 2 8% and 45% in CFB- and BFB-treated animals, respectively, mainly by mo dification of the cholesteryl ester fraction. In contrast, GFB signifi cantly increased total cholesterol (27%). No modification in the LDL p rotein or lipid content was introduced by fibrates, although GFB decre ased the proportion of LDL-triglycerides, at the expense of an increas e in total cholesterol. 4 The fatty acid species carried by VLDL and L DL were affected after fibrate treatment. In general, both particles s howed an increase in monounsaturated fatty acids (MUFA) (18:1) and a d ecrease in polyunsaturated fatty acids (PUFA) species (18:2 n-6, 20:4 n-6, 18:3 n-3, 20:5 n-3). As a consequence, the ratio of PUFA/(SFA + M UFA) for the whole lipoproteins was markedly reduced. 5 The degree of copper-induced VLDL- and LDL-oxidation was assessed by means of the an alysis of lysine content, thiobarbituric acid reactive substances (TEA RS) production and conjugated dienes formation. Lipoproteins obtained from fibrate-treated rats were more resistant to the oxidative challen ge. For each lipoprotein, BFB was the most effective drug, followed by CFB and GFB. 6 The observed antioxidant effect can be ascribed to two independent phenomena produced by fibrates: the reduction of the amou nt of substrate for the oxidation process due to their hypolipidemic a ctivity, and the alteration in the type of fatty acids transported by the lipoproteins towards an enrichment in species resistant to the oxi dation process. 7 As similar lipoprotein fatty acid changes have been reported after fibrate treatment in human subjects, an antioxidant eff ect of fibrates in human therapy, independent of their well known hypo lipidaemic activity, should be expected.