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Updated: Aug 15, 2026

Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein
Published on: October 12, 2017
Thiol-containing molecules interact with the myeloperoxidase/H2O2/chloride system to inhibit LDL oxidation
Pierre Van Antwerpen1, Karim Zouaoui Boudjeltia, Sajida Babar
1Laboratory of Pharmaceutical Chemistry, Institute of Pharmacy, Université Libre de Bruxelles, Brussels, Belgium.
Abstract:
Oxidized low-density lipoproteins (LDL) accumulate in the vascular wall and promote a local inflammatory process contributing to the progression of atheromatous plaque. The key role of myeloperoxidase (MPO) in this process has been documented and the enzyme has been involved in the oxidative modification of apolipoprotein B-100 in the intima and at the surface of endothelial cells. As the inhibition of this last phenomenon could be of relevance in pharmacological interventions, thiol-containing molecules such as glutathione, captopril, and N-acetylcysteine (NAC) and its lysinate salt (NAL) were tested in this system and their properties were compared with those of flufenamic acid (control). This last compound already demonstrated an inhibition of the production of HOCl by MPO and a more intense inhibition of MPO activity than glutathione, NAC, NAL, and captopril. However, NAC and NAL inhibited the oxidative modification of LDL more intensively than captopril and glutathione whereas flufenamic acid had no comparable inhibiting effect. This could be related to the presence of LDL close to the catalytic site of the enzyme. NAC and NAL therefore appeared as the most efficient inhibitors probably as a consequence of their relatively small size. The relevance of such effects has to be documented by in vivo studies.
Insights
N-acetylcysteine (NAC) and its lysinate salt (NAL) effectively inhibit oxidized low-density lipoprotein (LDL) modification, a key factor in atheromatous plaque progression. These smaller thiol-containing molecules show greater efficacy than larger ones, suggesting potential therapeutic benefits.
Area of Science:
- Cardiovascular Research
- Biochemistry
- Pharmacology
Background:
- Oxidized low-density lipoproteins (LDL) contribute to vascular inflammation and atheromatous plaque development.
- Myeloperoxidase (MPO) plays a crucial role in LDL oxidative modification within the vascular wall.
- Inhibiting MPO's oxidative activity on apolipoprotein B-100 is a potential therapeutic strategy.
Purpose of the Study:
- To evaluate the efficacy of thiol-containing molecules (glutathione, captopril, N-acetylcysteine (NAC), N-acetylcysteine lysinate (NAL)) in inhibiting MPO-mediated LDL oxidation.
- To compare the inhibitory properties of these molecules with flufenamic acid, a known MPO inhibitor.
Main Methods:
- In vitro assessment of MPO activity and its effect on LDL oxidation.
- Comparison of inhibition efficacy among glutathione, captopril, NAC, NAL, and flufenamic acid.
Main Results:
- Flufenamic acid inhibited MPO activity and HOCl production more effectively than thiol-containing molecules.
- NAC and NAL demonstrated superior inhibition of LDL oxidative modification compared to captopril and glutathione.
- The smaller size of NAC and NAL may contribute to their enhanced inhibitory effect on LDL oxidation.
Conclusions:
- NAC and NAL are potent inhibitors of MPO-driven LDL oxidation.
- The findings suggest NAC and NAL as promising candidates for pharmacological intervention in atherosclerosis.
- Further in vivo studies are warranted to confirm the therapeutic relevance of these findings.
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