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Cited by 1,252

The DOI matches its Crossref record.

Antioxidant defenses and lipid peroxidation in human blood plasma.

Open access
Frei, B, Stocker, R, Ames, B N·1988·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.85.24.9748
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Abstract

The temporal disappearance in human blood plasma of endogenous antioxidants in relation to the appearance of various classes of lipid hydroperoxides measured by HPLC postcolumn chemiluminescence detection has been investigated under two types of oxidizing conditions. Exposure of plasma to aqueous peroxyl radicals generated at a constant rate leads immediately to oxidation of endogenous ascorbate and sulfhydryl groups, followed by sequential depletion of bilirubin, urate, and alpha-tocopherol. Stimulating polymorphonuclear leukocytes in plasma initiates very rapid oxidation of ascorbate, followed by partial depletion of urate. Once ascorbate is consumed completely, micromolar concentrations of hydroperoxides of plasma phospholipids, triglycerides, and cholesterol esters appear simultaneously, even though sulfhydryl groups, bilirubin, urate, and alpha-tocopherol are still present at high concentrations. Nonesterified fatty acids, the only lipid class in plasma not transported in lipoproteins but bound to albumin, are preserved from peroxidative damage even after complete oxidation of ascorbate, most likely due to site-specific antioxidant protection by albumin-bound bilirubin and possibly by albumin itself. Thus, in plasma ascorbate and, in a site-specific manner, bilirubin appear to be much more effective in protecting lipids from peroxidative damage by aqueous oxidants than all the other endogenous antioxidants. Hydroperoxides of linoleic acid, phosphatidylcholine, and cholesterol added to plasma in the absence of added reducing substrates are degraded, in contrast to hydroperoxides of trilinolein and cholesterol linoleate. These findings indicate the presence of a selective peroxidase activity operative under physiological conditions. Our data suggest that in states of leukocyte activation and other types of acute or chronic oxidative stress such a simple regimen as controlled ascorbate supplementation could prove helpful in preventing formation of lipid hydroperoxides, some of which cannot be detoxified by endogenous plasma activities and thus might cause damage to critical targets.

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Metadata

Authors
Frei, B., Stocker, R., & Ames, B. N.
Venue
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Published
1988-12
Volume
85
Issue
24
Pages
9748-9752
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.85.24.9748
OpenAlex
W2089772634
Cited by
1,252
References
0
FWCI
19.39
Type
journal article
Language
en
Open access
green

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