Antioxidant defenses and lipid peroxidation in human blood plasma

Antioxidant defenses and lipid peroxidation in human blood plasma

1988

E00006

The temporal disappearance In human blood plasma of endogenous antloxidants 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 polymorphonucleor leukocytes in plasma initiates very rapid oxidation of ascorbate, followed by partial depletion of urate. Once aseorbate is consumed completely, micromolar concentrations of hydroperoxides of plasma pbosphollpids, triglycerides, and cholesterol esters appear simultaneously, even though sulfhydryl groups, billrubin, urate, and alpha-tocopherol are still present at high concentrations. Nonesterified fatty acids, the only Upld class in plasma not transported in ]lpeprotdns 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 pcroxidative 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 aseorbate 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.

v.85:9748-9752, NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, PROCEEDINGS

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