4.6 Article

Effects of cyclodextrins on the structure of LDL and its susceptibility to copper-induced oxidation

Journal

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 91, Issue -, Pages 183-189

Publisher

ELSEVIER
DOI: 10.1016/j.ejps.2016.04.037

Keywords

Cyclodextrin; Atherosclerosis; Low-density lipoprotein (LDL); Atomic force microscopy (AFM); LDL oxidation

Funding

  1. National Natural Science Foundation of China [31260205, 81560083]
  2. Natural Science Foundation of Jiangxi Province [20151BAB205005]

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Cyclodextrins (CDs) have long been widely used as drug/food carriers and were recently developed as drugs for the treatment of diseases (e.g. Niemann-Pick C1 and cancers). It is unknown whether cyclodextrins may influence the structure of low-density lipoprotein (LDL), its susceptibility to oxidation, and atherogenesis. In this study, four widely used cyclodextrins including alpha-CD,beta-CD, and two derivatives of beta-CD (HP beta CD and M beta CD) were recruited. Interestingly, agarose gel electrophoresis (staining lipid and protein components of LDL with Sudan Black B and Coomassie brilliant blue, respectively but simultaneously) shows that cyclodextrins at relatively high concentrations caused disappearance of the LDL band and/or appearance of an additional protein-free lipid band, implying that cyclodextrins at relatively high concentrations can induce significant electrophoresis-detectable lipid depletion of LDL. Atomic force microscopy (AFM) detected that M beta CD (as a representative of cyclodextrins) induced size decrease of LDL particles in a dose-dependent manner, further confirming the lipid depletion effects of cyclodextrins. Moreover, the data from agarose gel electrophoresis, conjugated diene formation, MDA production, and amino group blockage of copper-oxidized LDL show that cyclodextrins can impair LDL susceptibility to oxidation. It implies that cyclodextrins probably help to inhibit atherogenesis by lowering LDL oxidation. (C) 2016 Elsevier B.V. All rights reserved.

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