Forum: role of oxidation in atherosclerosis
Indices of lipid peroxidation in vivo: strengths and limitations

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Abstract

Oxidant stress has been widely implicated as a mechanism of disease, yet clinical trials of antioxidants have not included a biochemical basis for dose selection or patient inclusion. Many of the indices traditionally employed to assess lipid peroxidation have relied on measurements performed in ex vivo systems of questionable relevance to events in vivo. Commonly employed in vivo indices of lipid peroxidation are constrained by such issues as the nonspecificity or instability of the target anylate, contamination of the anylate by events ex vivo, and nonspecificity of analytical methodology. More recently, specific methodology based on mass spectrometry has been applied to both 4-hydroxynonenal and a variety of isoprostanes in human biological fluids. Measurement of these compounds in urine reflects lipid peroxidation in vivo and offers a noninvasive approach that may be readily applied to clinical trials.

Keywords

Oxidant stress
Isoprostane
Eicosanoid
Aldehydes
Lipids
Peroxidation
Free radical

Abbreviations

AA
arachidonic acid
FR
free radical
DNA
deoxyribonucleic acid
GC/MS
gas chromatography/mass spectrometry
4-HNE
4-hydroxynonenal
HPLC
high-performance liquid chromatography
ICAM
intercellular adhesion molecule
iPs
isoprostanes
LDL
low-density lipoprotein
MDA
malondialdehyde
PUFA
polyunsaturated fatty acids
PPAR
peroxisomal proliferator receptor
RNA
ribonucleic acid
TBARS
thiobarbituric acid
TP
thromboxane A2 receptor
UV
ultraviolet
VCAM
cellular adhesion molecule

Cited by (0)

1

Dr. Meagher is an Assistant Professor in the Division of Experimental Therapeutics of the Department of Medicine at the University of Pennsylvania. Her interests are in the role of lipid peroxidation in alcohol-induced liver disease and in the clinical pharmacology of antioxidants. She is the Associate Director of the Cardiovascular Risk and Prevention Program and holds a Clinical Associate Physician Award from the National Institutes of Health.

2

Dr. FitzGerald is the Chair of Pharmacology and directs the Center for Experimental Therapeutics and the GCRC at the University of Pennsylvania. He has a long-standing interest in the analytical biochemistry and pharmacology of bioactive lipids. He is the Robinette Foundation Professor of Cardiovascular Medicine.