Detection and inhibition of lipid-derived radicals in low-density lipoprotein

Free Radic Biol Med. 2017 Dec:113:487-493. doi: 10.1016/j.freeradbiomed.2017.10.388. Epub 2017 Oct 28.

Abstract

Oxidized low density lipoprotein (Ox-LDL) is implicated in a variety of oxidative diseases. To clarify the mechanisms involved and facilitate the investigation of therapeutics, we previously developed a detection method for lipid-derived radicals using the fluorescent probe 2,2,6-trimethyl-6-pentyl-4-(4-nitrobenzo[1,2,5]oxadiazol-7-ylamino)piperidine-1-oxyl (NBD-Pen). In this study, NBD-Pen was used to detect lipid-derived radicals in Ox-LDL from in vitro and in vivo samples using an iron overloaded mouse model. By following the timeline of lipid radical generation using this method, the iron overloaded mice could be successfully treated with the antioxidant Trolox, resulting in successful lowering of the plasma lipid peroxidation, aspartate transaminase and alanine transaminase levels. Furthermore, using a combination therapy of the chelating agent deferoxamine (DFX) and Trolox, liver injury and oxidative stress markers were also reduced in iron overloaded mice. The NBD-Pen method is highly sensitive as well as selective and is suitable for targeting minimally modified LDL compared with other existing methods.

Keywords: Antioxidant; Iron overload; Lipid; Low-density lipoprotein; Radical; Thalassemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Chloro-7-nitrobenzofurazan / analogs & derivatives
  • 4-Chloro-7-nitrobenzofurazan / chemistry
  • Alanine Transaminase / blood
  • Animals
  • Antioxidants / pharmacology*
  • Aspartate Aminotransferases / blood
  • Chromans / pharmacology
  • Cyclic N-Oxides / chemistry
  • Deferoxamine / pharmacology
  • Disease Models, Animal
  • Fluorescent Dyes / chemistry
  • Free Radicals / antagonists & inhibitors
  • Free Radicals / metabolism
  • Humans
  • Iron / metabolism*
  • Iron Overload / drug therapy*
  • Iron Overload / metabolism
  • Iron Overload / pathology
  • Lipid Peroxidation / drug effects
  • Lipoproteins, LDL / blood*
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Oxidative Stress
  • Spectrometry, Fluorescence

Substances

  • 2,2,6-trimethyl-4-(4-nitrobenzo(1,2,5)oxadiazol-7-ylamino)-6-pentylpiperidine-1-oxyl
  • Antioxidants
  • Chromans
  • Cyclic N-Oxides
  • Fluorescent Dyes
  • Free Radicals
  • Lipoproteins, LDL
  • oxidized low density lipoprotein
  • Iron
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • 4-Chloro-7-nitrobenzofurazan
  • Deferoxamine
  • 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid