Thiol-containing molecules interact with the myeloperoxidase/H2O2/chloride system to inhibit LDL oxidation.
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.
Van Antwerpen
Pierre
P
Laboratory of Pharmaceutical Chemistry, Institute of Pharmacy, Université Libre de Bruxelles, Brussels, Belgium.
Boudjeltia
Karim Zouaoui
KZ
Babar
Sajida
S
Legssyer
Ilham
I
Moreau
Patrick
P
Moguilevsky
Nicole
N
Vanhaeverbeek
Michel
M
Ducobu
Jean
J
Nève
Jean
J
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000737:chemistry; D000975:Antioxidants / Q000737:chemistry*; D002216:Captopril / Q000737:chemistry; D002712:Chlorides / Q000737:chemistry; D005439:Flufenamic Acid / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000737:chemistry*; D008239:Lysine / Q000031:analogs & derivatives / Q000737:chemistry; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D000975:Antioxidants; D002712:Chlorides; D008077:Lipoproteins, LDL; C086501:N-acetylcysteine lysinate; D013438:Sulfhydryl Compounds; C099252:oxidized low density lipoprotein; D005439:Flufenamic Acid; D002216:Captopril; D006861:Hydrogen Peroxide; D009195:Peroxidase; D005978:Glutathione; D008239:Lysine; D000111:Acetylcysteine