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The importance of lipid solubility in antioxidants and free radical generating systems for determining lipoprotein proxidation.
Free Radic Biol Med. 1999 Jun; 26(11-12):1524-30.FR

Abstract

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 microM) and lazaroid (IC50 = 5.0 microM) were more effective in inhibiting lipid peroxidation caused by a Fe-ADP free radical generating system than vitamin C (IC50 = 5.2 x 10(3) microM) and trolox (IC5 = 1.2 x 10(3) microM). 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.

Authors+Show Affiliations

Division of Stroke and Vascular Disease, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10401618

Citation

Massaeli, H, et al. "The Importance of Lipid Solubility in Antioxidants and Free Radical Generating Systems for Determining Lipoprotein Proxidation." Free Radical Biology & Medicine, vol. 26, no. 11-12, 1999, pp. 1524-30.
Massaeli H, Sobrattee S, Pierce GN. The importance of lipid solubility in antioxidants and free radical generating systems for determining lipoprotein proxidation. Free Radic Biol Med. 1999;26(11-12):1524-30.
Massaeli, H., Sobrattee, S., & Pierce, G. N. (1999). The importance of lipid solubility in antioxidants and free radical generating systems for determining lipoprotein proxidation. Free Radical Biology & Medicine, 26(11-12), 1524-30.
Massaeli H, Sobrattee S, Pierce GN. The Importance of Lipid Solubility in Antioxidants and Free Radical Generating Systems for Determining Lipoprotein Proxidation. Free Radic Biol Med. 1999;26(11-12):1524-30. PubMed PMID: 10401618.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The importance of lipid solubility in antioxidants and free radical generating systems for determining lipoprotein proxidation. AU - Massaeli,H, AU - Sobrattee,S, AU - Pierce,G N, PY - 1999/7/13/pubmed PY - 1999/7/13/medline PY - 1999/7/13/entrez SP - 1524 EP - 30 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 26 IS - 11-12 N2 - 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 microM) and lazaroid (IC50 = 5.0 microM) were more effective in inhibiting lipid peroxidation caused by a Fe-ADP free radical generating system than vitamin C (IC50 = 5.2 x 10(3) microM) and trolox (IC5 = 1.2 x 10(3) microM). 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. SN - 0891-5849 UR - https://www.unboundmedicine.com/medline/citation/10401618/The_importance_of_lipid_solubility_in_antioxidants_and_free_radical_generating_systems_for_determining_lipoprotein_proxidation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(99)00018-0 DB - PRIME DP - Unbound Medicine ER -