Tetradecylthioacetic acid inhibits the oxidative modification of low density lipoprotein and 8-hydroxydeoxyguanosine formation in vitro

Z A Muna, K Doudin, J Songstad, R J Ulvik, R K Berge

Research output: Contribution to journalArticle

Abstract

Oxidative modification of low-density lipoprotein (LDL) is thought to play a key role in the formation of foam cells and in initiation and progression of atherosclerotic plaque. The hypolipidemic 3-thia fatty acids contain a sulfur atom and might therefore possess reducing (antioxidant) properties. Consequently, the effects of 3-thia fatty acids on the susceptibility of LDL particles to undergo oxidative modification in vitro were studied. Tetradecylthioacetic acid (TTA), incorporated into the LDL particle and increased the lag time of copper ion induced LDL oxidation in a dose-dependent manner, 80 mumol/L TTA reduced the generation of lipid peroxides during copper ion induced LDL oxidation (for 2 hours) by 100%, 2,2'-azobis-(2,4-dimethylvaleronitrile) induced LDL oxidation by 64%, and 2,2'-azobis-(2-amidinopropane hydrochloride) induced LDL oxidation (for 6 hours) by 21%. The electrophoretic mobility of the oxidized LDL was reduced by TTA in both copper ion and azo-compounds initiated oxidation. This fatty acid analogue was effectively able to reduce in a dose dependent manner the formation of 8-hydroxydeoxyguanosine from 2-deoxyguanosine with ascorbic acid as the radical producer. TTA bound copper(II) ions and did not reduce copper(II) to copper(I). It failed to scavenge the 1,1-diphenyl-2-picrylhydrazyl radicals. The results suggest that the modification of LDL in the lipid and protein moieties can be significantly reduced by TTA. This acid may exert its antioxidant effect partially through metal ion binding and through free radical scavenging.
Original languageEnglish
Pages (from-to)3255-3262
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular biology
Volume17
Issue number11
DOIs
Publication statusPublished - Nov 1997

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LDL Lipoproteins
Copper
Ions
Fatty Acids
Azo Compounds
Antioxidants
Foam Cells
Deoxyguanosine
In Vitro Techniques
8-oxo-7-hydrodeoxyguanosine
1-(carboxymethylthio)tetradecane
Lipid Peroxides
Atherosclerotic Plaques
Sulfur
Ascorbic Acid
Free Radicals
Metals
Lipids
Acids
Proteins

Keywords

  • amidines
  • antioxidants
  • ascorbic acid
  • azo compounds
  • copper
  • DNA damage
  • deoxyguanosine
  • dose-response relationship, Drug
  • free radical scavengers
  • free radicals
  • humans
  • kinetics
  • lipid peroxidation
  • lipoproteins, LDL
  • nitriles
  • oxidants
  • oxidation-reduction
  • oxidative stress
  • sulfides

Cite this

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title = "Tetradecylthioacetic acid inhibits the oxidative modification of low density lipoprotein and 8-hydroxydeoxyguanosine formation in vitro",
abstract = "Oxidative modification of low-density lipoprotein (LDL) is thought to play a key role in the formation of foam cells and in initiation and progression of atherosclerotic plaque. The hypolipidemic 3-thia fatty acids contain a sulfur atom and might therefore possess reducing (antioxidant) properties. Consequently, the effects of 3-thia fatty acids on the susceptibility of LDL particles to undergo oxidative modification in vitro were studied. Tetradecylthioacetic acid (TTA), incorporated into the LDL particle and increased the lag time of copper ion induced LDL oxidation in a dose-dependent manner, 80 mumol/L TTA reduced the generation of lipid peroxides during copper ion induced LDL oxidation (for 2 hours) by 100{\%}, 2,2'-azobis-(2,4-dimethylvaleronitrile) induced LDL oxidation by 64{\%}, and 2,2'-azobis-(2-amidinopropane hydrochloride) induced LDL oxidation (for 6 hours) by 21{\%}. The electrophoretic mobility of the oxidized LDL was reduced by TTA in both copper ion and azo-compounds initiated oxidation. This fatty acid analogue was effectively able to reduce in a dose dependent manner the formation of 8-hydroxydeoxyguanosine from 2-deoxyguanosine with ascorbic acid as the radical producer. TTA bound copper(II) ions and did not reduce copper(II) to copper(I). It failed to scavenge the 1,1-diphenyl-2-picrylhydrazyl radicals. The results suggest that the modification of LDL in the lipid and protein moieties can be significantly reduced by TTA. This acid may exert its antioxidant effect partially through metal ion binding and through free radical scavenging.",
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author = "Muna, {Z A} and K Doudin and J Songstad and Ulvik, {R J} and Berge, {R K}",
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Tetradecylthioacetic acid inhibits the oxidative modification of low density lipoprotein and 8-hydroxydeoxyguanosine formation in vitro. / Muna, Z A; Doudin, K; Songstad, J; Ulvik, R J; Berge, R K.

In: Arteriosclerosis, Thrombosis, and Vascular biology, Vol. 17, No. 11, 11.1997, p. 3255-3262.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Tetradecylthioacetic acid inhibits the oxidative modification of low density lipoprotein and 8-hydroxydeoxyguanosine formation in vitro

AU - Muna, Z A

AU - Doudin, K

AU - Songstad, J

AU - Ulvik, R J

AU - Berge, R K

PY - 1997/11

Y1 - 1997/11

N2 - Oxidative modification of low-density lipoprotein (LDL) is thought to play a key role in the formation of foam cells and in initiation and progression of atherosclerotic plaque. The hypolipidemic 3-thia fatty acids contain a sulfur atom and might therefore possess reducing (antioxidant) properties. Consequently, the effects of 3-thia fatty acids on the susceptibility of LDL particles to undergo oxidative modification in vitro were studied. Tetradecylthioacetic acid (TTA), incorporated into the LDL particle and increased the lag time of copper ion induced LDL oxidation in a dose-dependent manner, 80 mumol/L TTA reduced the generation of lipid peroxides during copper ion induced LDL oxidation (for 2 hours) by 100%, 2,2'-azobis-(2,4-dimethylvaleronitrile) induced LDL oxidation by 64%, and 2,2'-azobis-(2-amidinopropane hydrochloride) induced LDL oxidation (for 6 hours) by 21%. The electrophoretic mobility of the oxidized LDL was reduced by TTA in both copper ion and azo-compounds initiated oxidation. This fatty acid analogue was effectively able to reduce in a dose dependent manner the formation of 8-hydroxydeoxyguanosine from 2-deoxyguanosine with ascorbic acid as the radical producer. TTA bound copper(II) ions and did not reduce copper(II) to copper(I). It failed to scavenge the 1,1-diphenyl-2-picrylhydrazyl radicals. The results suggest that the modification of LDL in the lipid and protein moieties can be significantly reduced by TTA. This acid may exert its antioxidant effect partially through metal ion binding and through free radical scavenging.

AB - Oxidative modification of low-density lipoprotein (LDL) is thought to play a key role in the formation of foam cells and in initiation and progression of atherosclerotic plaque. The hypolipidemic 3-thia fatty acids contain a sulfur atom and might therefore possess reducing (antioxidant) properties. Consequently, the effects of 3-thia fatty acids on the susceptibility of LDL particles to undergo oxidative modification in vitro were studied. Tetradecylthioacetic acid (TTA), incorporated into the LDL particle and increased the lag time of copper ion induced LDL oxidation in a dose-dependent manner, 80 mumol/L TTA reduced the generation of lipid peroxides during copper ion induced LDL oxidation (for 2 hours) by 100%, 2,2'-azobis-(2,4-dimethylvaleronitrile) induced LDL oxidation by 64%, and 2,2'-azobis-(2-amidinopropane hydrochloride) induced LDL oxidation (for 6 hours) by 21%. The electrophoretic mobility of the oxidized LDL was reduced by TTA in both copper ion and azo-compounds initiated oxidation. This fatty acid analogue was effectively able to reduce in a dose dependent manner the formation of 8-hydroxydeoxyguanosine from 2-deoxyguanosine with ascorbic acid as the radical producer. TTA bound copper(II) ions and did not reduce copper(II) to copper(I). It failed to scavenge the 1,1-diphenyl-2-picrylhydrazyl radicals. The results suggest that the modification of LDL in the lipid and protein moieties can be significantly reduced by TTA. This acid may exert its antioxidant effect partially through metal ion binding and through free radical scavenging.

KW - amidines

KW - antioxidants

KW - ascorbic acid

KW - azo compounds

KW - copper

KW - DNA damage

KW - deoxyguanosine

KW - dose-response relationship, Drug

KW - free radical scavengers

KW - free radicals

KW - humans

KW - kinetics

KW - lipid peroxidation

KW - lipoproteins, LDL

KW - nitriles

KW - oxidants

KW - oxidation-reduction

KW - oxidative stress

KW - sulfides

UR - http://atvb.ahajournals.org/content/17/11/3255.abstract

U2 - 10.1161/01.ATV.17.11.3255

DO - 10.1161/01.ATV.17.11.3255

M3 - Article

C2 - 9409320

VL - 17

SP - 3255

EP - 3262

JO - Arteriosclerosis, Thrombosis, and Vascular biology

JF - Arteriosclerosis, Thrombosis, and Vascular biology

SN - 1079-5642

IS - 11

ER -