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Review: the oxidant/antioxidant balance during regular low density lipoprotein apheresis
V Schettler1, H Methe, D Staschinsky
1Department of Nephrology and Rheumatology, Georg-August-University, Göttingen, Germany. vschett@gwdg.de
Insights
Low density lipoprotein (LDL) apheresis is a safe treatment for severe hypercholesterolemia, even in patients with chronic heart disease. This procedure does not increase oxidative stress, as LDL particles become more resistant to oxidation post-treatment.
Area of Science:
- Cardiovascular Medicine
- Biochemistry
- Nephrology
Background:
- Severe hypercholesterolemia is a risk factor for chronic heart disease (CHD).
- Extracorporeal treatments, including LDL apheresis, can induce oxidative stress.
- Oxidative modification of LDL may increase its atherogenic potential.
Purpose of the Study:
- To evaluate the safety of LDL apheresis concerning oxidative stress and LDL oxidation.
- To assess the impact of LDL apheresis on antioxidant levels and radical-mediated injury.
Main Methods:
- Analysis of leukocyte activation and inflammatory markers during LDL apheresis.
- Measurement of antioxidant levels (glutathione, antioxidant enzymes) in plasma, red cells, and granulocytes.
- Assessment of LDL oxidation resistance before and after apheresis.
Main Results:
- LDL apheresis did not lead to significant plasma lipid peroxidation.
- Plasma glutathione concentrations increased post-apheresis.
- Antioxidant enzyme activity remained largely unaffected.
- LDL isolated after apheresis exhibited increased resistance to oxidation.
Conclusions:
- LDL apheresis appears safe regarding radical-mediated injury.
- The procedure does not exacerbate oxidative stress.
- Increased resistance of LDL to oxidation suggests a potentially beneficial effect.
Abstract:
Low density lipoprotein (LDL) apheresis is a safe procedure to treat severe hypercholesterolemia in patients with chronic heart disease (CHD). However, both hypercholesterolemia and extracorporeal treatment have been associated with oxidative stress. Even though LDL lowering has been proven to reduce CHD, the oxidative modification of LDL has been suggested to render these lipoproteins more atherogenic. It is therefore important to know whether LDL apheresis is safe with respect to oxidative stress including LDL oxidation. The contact of living cells such as leukocytes with artificial surfaces during extracorporeal treatment induces the liberation of various chemokines and cytokines as well as oxygen-derived radicals also known as respiratory burst. These effects justify the consideration of leukocyte activation resulting from extracorporeal treatment as an inflammatory reaction. In extracorporeal circuits such as those used for hemodialysis, the release of oxygen radicals has been shown and depends on the fiber material used in the dialyzer membranes. Reactive oxygen radicals can interact with different cell components such as carbohydrates, DNA, proteins, and lipids. Antioxidants in the form of low molecular weight molecules such as glutathione or radical scavenging enzymes such as superoxide dismutase offer protection against the damaging effects of prooxidants. The disturbed balance between prooxidants and antioxidants is considered as oxidative stress. Therefore, either an increase in oxygen radical formation or a decrease of antioxidants will lead to oxidative stress. During LDL apheresis, a decrease of low molecular weight antioxidants has been reported. In contrast, we have observed an increase in plasma glutathione concentrations but no severe reduction in the activity of antioxidant enzymes in plasma, red cells, or granulocytes, which may explain the lack of plasma lipid peroxidation shown during this kind of extracorporeal treatment. In addition, LDL isolated at the end of apheresis procedures are more resistant to oxidation. These findings suggest that LDL apheresis is safe with respect to radical mediated injury.