The importance of lipid solubility in antioxidants and free radical generating systems for determining lipoprotein peroxidation

Hamid Massaeli, Salisha Sobrattee, Grant N. Pierce

Research output: Contribution to journalArticle

53 Citations (Scopus)


The oxidative modification of low-density lipoprotein (LDL) plays an important role in atherosclerosis. Protecting LDL from oxidation has been shown to reduce the risk of coronary heart disease. In this study, we compared the protective effects of two lipophilic antioxidants (vitamin E and lazaroid) with two hydrophilic antioxidants (trolox and vitamin C) in the presence of several different free radical generating systems. Vitamin E (IC50 = 5.9 μM) and lazaroid (IC50 = 5.0 μM) were more effective in inhibiting lipid peroxidation caused by a Fe-ADP free radical generating system than vitamin C (IC50 = 5.2 x 103 μM) and trolox (IC5 = 1.2 x 103 μM). Preincubation of lipoproteins with a lipophilic antioxidant increased the protective effect against various free radicals. Preincubation with hydrophilic antioxidants did not have an effect. We also tested the efficacy of the antioxidants when the free radicals were generated within the lipid or the aqueous environment surrounding the LDL. For this purpose, we used the peroxyl generating azo-compounds AMVN (2,2'-azobis(2,4- dimethylvaleronitrile)) and AAPH (2,2'azobis (2-amidinopropane) dihydrochloride). All of the antioxidants tested were more effective against free radicals generated in a water soluble medium than they were against free radicals generated in a lipid environment. In conclusion, our data demonstrate that lipid solubility is an important factor for both the antioxidant and the free radical generating systems in determining the extent of lipid peroxidation in LDL. Our data also demonstrate that antioxidant efficacy in one set of experimental conditions may not necessarily translate into a similar degree of protection in another set of conditions where lipophilicity is a variable.

Original languageEnglish
Pages (from-to)1524-1530
Number of pages7
JournalFree Radical Biology and Medicine
Issue number11-12
Publication statusPublished - 1 Jun 1999
Externally publishedYes



  • Atherosclerosis
  • Coronary artery disease
  • Free radicals
  • Lazaroid
  • Lipid peroxidation
  • Low-density lipoprotein
  • Oxygen derived free radicals
  • Trolox
  • Vitamin C
  • Vitamin E

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this