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Abstract
An antioxidant defense system consisting of enzymes and non-enzymatic compounds prevents
oxidative damage of lipoproteins in the plasma. When the activity of this system decreases
or the reactive oxygen species (ROS) production increases, an oxidative stress may
occur. Since fatty acids and triglyceride-rich emulsions can stimulate leukocytes
to produce ROS, it is conceivable that raised plasma triglyceride-rich lipoproteins
such as very low density lipoprotein (VLDL) may overload the antioxidant system. To
test this hypothesis, we selected 14 patients with combined hyperlipidemia (HLP),
in whom low density lipoprotein (LDL) and VLDL levels are elevated, as well as 18
hypercholesterolemic patients (HCH) with increased LDL levels and 19 controls (NL)
to examine the trend for an imbalance between the production of oxidative species
and the antioxidant defense system as challenged by increased plasma lipids. With
this goal, plasma lipoprotein lipid fractions were determined and correlated with
the release of ROS by leukocytes monitored by luminol-enhanced chemiluminescence.
Plasma β-carotene, α-tocopherol, lycopene and the lipoprotein lipid hydroperoxides
were determined by high pressure liquid chromatography with electrochemical detection.
HLP had lower plasma superoxide dismutase (SOD) activity (0.04 and 0.11 U/mg protein;
P < 0.05) as well as lower concentrations of lycopene (0.1 and 0.2 nmol/mg cholesterol;
P < 0.05) and β-carotene (0.8 and 2.7 nmol/mg cholesterol; P < 0.05) in the plasma, as compared with NL. Moreover, HLP showed the highest ROS
production by resting mononuclear leukocytes (MN) among the three study groups. When
the results of the subjects of the three groups were taken together, the plasma triglyceride
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 positively 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) cholesterol 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 susceptibility to copper (II) oxidation was not different among the
three groups. Regarding LDL, there was an increased oxidizability in HLP group. 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 controls (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 antioxidant defense system were also decreased. Our finding
that the leukocyte ROS production is positively correlated with either VLDL or LDL
triglycerides sheds light on a new aspect of the leukocyte activation and oxidative
stress in hyperlipidemia.
Keywords
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Article info
Publication history
Accepted:
February 28,
1995
Received in revised form:
January 26,
1995
Received:
June 6,
1994
Identification
Copyright
© 1995 Published by Elsevier Inc.
