Hydroperoxide metabolism in vitamin E-deficient hepatocytes. Studies on low-level chemiluminescence, lipid peroxidation, and glutathione status

Abstract

The role of vitamin E, the major lipid-soluble, chain-breaking antioxidant in human blood (1,2), has been recently discussed (3). Vitamin E pretreatment has been reported to protect against the hepatocyte damage (4) caused by a diffusible product of lipid peroxidation, 4-OH-2,3-trans-nonenal (5), and also to be associated with a rise in red blood cell glutathione (6). This study is concerned with some aspects of hydroperoxide metabolism in vitamin Edeficient hepatocytes. Two different experimental models for lipid peroxidation were used: (a) the hydroperoxide-induced lipid peroxidation, and (b) the iron-induced lipid peroxidation. The former omits the typical initiation phase of the free radical chain process of peroxidation, because of the capability of oxidized hemoproteins, notably cytochrome P-450, to catalyze the homolytic (7) and/or heterolytic (8) scission of hydroperoxides. The latter is characterized by the occurrence of a lag phase (9-11), probably reflecting the presence of vitamin E (12). The oxidative challenge imposed to isolate hepatocytes by these two experimental models was evaluated in terms of (a) low-level chemiluminescence, which provides a continuous monitoring of free radical oxidative interactions (13,14) and (b) the glutathione status of the cell.