Kinetics of lipid radical formation in lipoproteins from β-thalassemia: Implication of cholesteryl esters and α-tocopherol

• Published in: Biomedicine & pharmacotherapy Vol. 154; p. 113624
• Main Authors: Lerksaipheng, Pakawit, Paiboonsukwong, Kittiphong, Sanvarinda, Pimtip, Leuchapudiporn, Rataya, Yamada, Ken-Ichi, Morales, Noppawan Phumala
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.10.2022; Elsevier
• Subjects: Cholesteryl esters; Iron overload; Lipid peroxidation; Lipid radicals; Lipoproteins; β-thalassemia; Iron overload; Lipid peroxidation; Cholesteryl esters; Lipoproteins; Lipid radicals; β-thalassemia
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.113624

Vascular complications in β-thalassemia are associated with oxidative modification of lipoproteins under high oxidative stress. The lipid components of lipoproteins are oxidized via lipid peroxidation and produce lipid radicals (L•) as the key initial intermediates. Modification of lipid components, therefore, might result in alterations in the rate and products of lipid peroxidation. In this study, the kinetics of L• formation during the 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH)- and hemin-induced oxidation of low-density and high-density lipoproteins (LDL and HDL) from β-thalassemia patients and healthy volunteers were investigated using a specific and sensitive fluorescence probe for L•. Kinetic parameters, including initial lag time, propagation rate and total L• production, were calculated by monitoring a fluorescence-active NBD-Pen-L• adduct. Oxidation of thalassemia lipoproteins exhibited a significantly shorter lag time but a slower propagation rate of L• formation when compared with healthy lipoproteins. LDL showed higher resistance to oxidation during the initiation phase but higher L• formation than HDL. Our results indicated that the levels of α-tocopherol determined the initial lag time, whereas the levels of core lipids and cholesteryl esters, especially cholesteryl linoleate (CL), determined the propagation rate and total L• production. The difference in potency of AAPH and hemin supported that hemin preferentially targeted core lipids. Moreover, analysis of 13-hydroxyoctadecadienoic acid cholesteryl ester (13-HODE-CE)/CE ratio indicated that thalassemia lipoproteins have higher susceptibility to oxidation than healthy lipoproteins. In conclusion, our findings suggested that CL and α-tocopherol were implicated in the susceptibility of lipoproteins to lipid peroxidation in physiological and pathological conditions of β-thalassemia. [Display omitted] •A fluorescence probe, NBD-Pen, sensitively monitored lipid radical (L•) formation in lipoproteins. Kinetic profiles and the amount of L• depended on the target site of lipoprotein oxidation.•Kinetic profiles of L• formation demonstrated that contents of cholesteryl linoleate and α-tocopherol determine the susceptibility of lipid oxidation in β-thalassemia lipoproteins.•Contents of α-tocopherol negatively correlated with the initial lag time, while cholesteryl linoleate level positively correlated with the propagation rate and the amount of L•.