Antioxidant defenses and lipid peroxidation in human blood plasma.

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 o!-tocopherol. Stimulating polymorphonuclear leukocytes in plasma initiates very rapid oxidation ofascorbate, 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 a-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.

Oxidative Stress-Induced Response of Some Endogenous Antioxidants in Schizophrenia

“…The two factors of aging and substance abuse are a reflection of increasing free radical load, where the level of bilirubin decreased in both these conditions contrary to the overall increase in all other groups. Here, it becomes pertinent to mention that bilirubin is transported as albumin bound complex in plasma [32] and it may be possible that the depleting plasma albumin levels are responsible for similar behavior of bilirubin [37].…”

Effects of intravenous supplementation with α-tocopherol in patients receiving total parenteral nutrition containing medium- and long-chain triglycerides

“…First, the end-products monitored in the in vitro methods account for only a fraction of the PUFA consumed during the lipid peroxidation process, about 10% in the case of MDA (Esterbauer et al, 1991). Second, factors in the microenvironment around the lipoprotein particle, such as vitamin C and bilirubin in plasma, can also influence the peroxidation process (Frei et al, 1988;Neuzil & Stocker, 1994). In comparison to the numerous studies all demonstrating a beneficial effect of vitamin E supplementation on lipoprotein peroxidation in vitro (Simons et al, 1996), the evidence on beneficial effects on peroxidation in vivo is still inconclusive and varies according to the type of peroxidation products being monitored.…”

Vitamin C modulation of H2O2-induced damage and iron homeostasis in human cells

“…Vitamin C (ascorbic acid, AA) is an important antioxidant in human plasma, where it acts as a scavenger of free radicals and protects against lipid peroxidation [12].…”