Influence of probucol on enhanced LDL oxidation after fish oil treatment of hypertriglyceridemic patients.

Abstract

The susceptibility of low-density lipoprotein (LDL) to oxidation was studied in hypertriglyceridemic men (5 with type III and 5 with type IV) at baseline on a low-saturated-fat, low-cholesterol diet, after 6 weeks of dietary supplementation with fish oil (Promega, 12 g/d), and after 6 weeks of fish oil combined with probucol (500 mg BID). The relative content of n-3 polyunsaturated fatty acids in plasma and LDL was increased during the two treatment periods, and a low a-tocopherol to n-3 polyunsaturated fatty acids ratio was observed. Plasma thiobarbituric acid-reactive substances (TBARS) levels were unchanged after 6 weeks of fish oil, but the ratio of lipid peroxides to the reduced triglyceride (TG) levels (MDA: TG) was significantly higher (P<.01). Addition of probucol lowered both absolute levels of TBARS (P<.01) and the MDA to TG ratio (P<.001). The susceptibility of LDL to Cu 2+ -catalyzed oxidation was evaluated over a 5-hour time course by determining TBARS formation, free amino group levels, and changes in LDL electrophoretic mobility. TBARS levels that were higher in native LDL (1.019«/< 1.050 g/mL) after 6 weeks offish oil than at baseline (P<.0l) were reduced 52.3±11.3% by the addition of probucol (P<.001). With fish oil alone, TBARS production after exposure of LDL to Cu

Influence of fish oil supplementation on in vivo and in vitro oxidation resistance of low-density lipoprotein in type 2 diabetes

“…However, these studies may have been underpowered due to the relatively large analytical variance of the assays that they employed. Other studies also using alternative methods found similar to us a decreased resistance of LDL to oxidation (Lussier-Cacan et al, 1993;Suzukawa et al, 1995;Higdon et al, 2001). Studies in which plasma concentrations of lipid peroxidation products were determined as a measure for in vivo lipid peroxidation found either no change or increased peroxidation after fish oil consumption.…”

“…Fish oil supplementation and LDL H Pedersen et al no effect of fish oil on plasma TBARS, while others showed increased plasma TBARS concentrations after fish oil supplementation (Lussier-Cacan et al, 1993;Suzukawa et al, 1995;Tsai & Lu, 1997). Higdon et al (2000) found no effect of fish oil supplementation on plasma MDA in nondiabetic subjects.…”

Can We Recommend Fish Oil for Hypertension?

“…In view of the atherogenic potential of oxidized LDL in man, an increase in LDL oxidation by fish oil in vivo may tend to diminish the overall anti-atherogenic effect of fish oil. Coadministration of probucol has been shown to prevent LDL oxidation by fish oil (Lussier-Cacan 1993) and Drevon (1992) suggests that the potential of high n-3 PUFA intakes to oxidize lipids may increase the requirement for Vitamin E. Thus addition of adequate amounts of Vitamin E or other antioxidants to the fish oil supplements may be necessary to offset this potentially adverse effect.…”

Effects of fish oil fatty acids on plasma lipids and lipoproteins and oxidant-antioxidant imbalance in healthy subjects

“…There was no reduction of arachidonic acid in plasma nor in LDL. Suzukawa [5], in hypertensive subjects, and LussierCacan [38], in hypertriglyceridaemic subjects, found a decrease in arachidonic acid in LDL, but n-3 PUFA intake was higher and supplementation duration was longer (3.4 and 4.8 g/day n-3 fatty acids for 6 and 8 weeks, respectively).…”

“…Indeed, vitamin E supplementation has been shown to counteract the ®sh oil-induced increase in LDL oxidizability [29,44]. Panzetta & Lussier-Cacan observed the same effects, but their ®sh oil preparation contained retinol with vitamin E [45] or probucol [38].…”