LIPOPROTEIN COMPOSITION AND OXIDATIVE MODIFICATION DURING THERAPY WITH GEMFIBROXIL AND LOVASTATIN IN PATIENTS WITH COMBINED HYPERLIPIDEMIA

Aims To evaluate the resistance to oxidation of human lipoproteins aft er hypolipidaemic therapy. Methods VLDL and LDL samples were obtained from patients with Familial Combined Hyperlipidaemia included in a ran domized, double-blind, cross-over study, with 8 weeks of active treatm ent (gemfibrozil, 600 mg twice daily, or lovastatin, 40 mg daily) and a 4-week wash-out period. Oxidation related analytes after Cu-induced oxidation of VLDL and LDL have been investigated. Further, in order to relate possible changes in oxidative behaviour to lipoprotein composi tion, the proportion of the lipid species transported by lipoproteins (triglycerides, phospholipids, and cholesteryl esters), the molar comp osition of fatty acids for each lipoprotein lipid, and the content of antioxidant vitamins in plasma (vitamin C) and Lipoproteins (vitamin E ) have been studied. Results Both drugs reduced the plasma concentrati on of apo-B lipoproteins (-23% gemfibrozil, -26% lovastatin), but wher eas lovastatin affected mainly LDL-cholesterol (-30%), gemfibrozil red uced triglycerides (-49%) and VLDL-cholesterol (-48%). Lovastatin trea tment had no effect on the lipid and protein composition, the fatty ac id profile, or the vitamin E content of either VLDL or LDL; Likewise, lipoprotein oxidation markers (Cu-induced conjugated dienes, thiobarbi turic acid reactive substances formation, and lysine residues) were si milar before and after lovastatin treatment. Gemfibrozil therapy also had no effect on Lipoprotein oxidation; nevertheless, it consistently: a) decreased the proportion of LDL-triglycerides (-32%), and b) incre ased the proportion (molar%) of 18:3 n-6 in VLDL triglycerides (+140%) , phospholipids (+363%) and cholesteryl esters (+53%). Conclusions Bas ed on these results, lovastatin and gemfibrozil do not adversely affec t Lipoprotein oxidation in patients with mixed dyslipidaemia. In the c ase of gemfibrozil, this occurs in spite of an increased proportion of some polyunsaturated fatty acids in VLDL. In the context of a fixed d ietary intake, such modifications suggest that the drug influences liv er enzyme activities involved in fatty acid chain synthesis (elongases and desaturases).