EVALUATION OF OXIDATIVE STRESS IN PATIENTS WITH HYPERLIPIDEMIA

An antioxidant defense system consisting of enzymes and non-enzymatic compounds prevents oxidative damage of lipoproteins in the plasma. Whe n the activity of this system decreases or the reactive oxygen species (ROS) production increases, an oxidative stress may occur. Since fatt y acids and triglyceride-rich emulsions can stimulate leukocytes to pr oduce ROS, it is conceivable that raised plasma triglyceride-rich lipo proteins such as very low density lipoprotein (VLDL) may overload the antioxidant system. To test this hypothesis, we selected 14 patients w ith combined hyperlipidemia (HLP). in whom low density lipoprotein (LD L) and VLDL levels are elevated, as well as 18 hypercholesterolemic pa tients (HCH) with increased LDL levels and 19 controls (NL) to examine the trend for an imbalance between the production of oxidative specie s and the antioxidant defense system as challenged by increased plasma lipids. With this goal, plasma lipoprotein lipid fractions were deter mined and correlated with the release of ROS by leukocytes monitored b y luminol-enhanced chemiluminescence. Plasma beta-carotene, alpha-toco pherol, lycopene and the lipoprotein lipid hydroperoxides were determi ned by high pressure liquid chromatography with electrochemical detect ion. HLP had lower plasma superoxide dismutase (SOD) activity (0.04 an d 0.11 U/mg protein; P < 0.05) as well as lower concentrations of lyco pene (0.1 and 0.2 nmol/mg cholesterol; P < 0.05) and beta-carotene (0. 8 and 2.7 nmol/mg cholesterol; P < 0.05) in the plasma, as compared wi th NL. Moreover, HLP showed the highest ROS production by resting mono nuclear leukocytes (MN) among the three study groups, When the results of the subjects of the three groups were taken together, the plasma t riglyceride concentration was positively correlated to ROS release by resting polymorphonuclear leukocytes (PMN, r = 0.38, P = 0.04) and MN (r = 0.56, P < 0.005). Moreover, ROS release by resting MN was positiv ely correlated with VLDL (r = 0.47, P = 0.02) and LDL (r = 0.57, P = 0 .01) triglycerides. There was also a positive correlation between ROS release by stimulated PMN and VLDL (r = 0.44, P = 0.03) as well as LDL (r = 0.53, P = 0.01) triglycerides. High density lipoprotein (HDL) ch olesterol showed a negative correlation with ROS release by resting MN (r = -0.48, P = 0.02) and resting PMN (r = -0.49, P = 0.01). VLDL sus ceptibility to copper (II) oxidation was not different among the three groups. Regarding LDL, there was an increased oxidizability in HLP gr oup. Plasma ferritin, which may act as a source of catalytic iron for lipid peroxidation, was found to be greater in HLP and HCH than in con trols (P < 0.05). These results suggest that oxidative stress is more likely to occur in HLP than in NL and HCH, since in HLP the release of ROS by leukocytes was greater, while some components of their antioxi dant defense system were also decreased. Our finding that the leukocyt e ROS production is positively correlated with either VLDL or LDL trig lycerides sheds light on a new aspect of the leukocyte activation and oxidative stress in hyperlipidemia.