Hydroperoxide Metabolism: An Overview

Abstract

The well-documented generation of the oxygen intermediates O 2 - and H2O2 at a multiplicity of cellular sources in biological systems may lead to the production of the unstable and reactive oxygen species HO· and 1O2. These latter species are able to initiate a free radical chain reaction that leads to lipid and organic peroxide formation. The response of rat liver to hyperbaric oxygen, for which most of the physiological and biochemical parameters related to hydroperoxide metabolism have been verified, supports this interpretation. Increased oxygen tensions produce (1) increased O 2 - generation by the mitochondria and cytosolic enzymes; (2) increased H2O2 production in isolated mitochondria, microsomes and peroxisomes, and in isolated rat liver cells; (3) a very slight increase of H2O2 production in perfused liver and in the organ in situ, indicating in the latter case the protective role of the microvascular system; and (4) an increase in GSSG release from the perfused rat liver, which is especially marked in the tocopherol-deficient liver. Oxidized glutathione release, reflecting the presence of intracellular glutathione peroxidase substrates, affords a very sensitive assay for oxidative stress. Glutathione peroxidase turnover is linked to the main redox state of the cell by the NADPH-dependent glutathione reductase and the transhydrogenases. Chemiluminescence from perfused rat liver and from the isolated subcellular fractions is markedly stimulated by lipid hydroperoxides. Studies of chemiluminescence and ethane formation may prove useful approaches for understanding lipid peroxidation in intact systems.