Oxygen-Free Radicals: Potential Edema Mediators in Brain Injury

Abstract

During the past few decades, a large body of experimental data has accumulated indicating that the biological reduction of molecular oxygen could yield dangerously reactive-free radical intermediates [14]. In mammalian cells, various subcellular membranous structures and cytosolic compartments are sites of production of oxygen radicals [15]. It has been demonstrated that about 2%–5% of the electron flow in isolated mitochondria goes to produce superoxide (O₂•-) and hydrogen peroxide (H₂O₂) [3]. Under normal metabolic conditions, these oxygen radicals formed by mitochondria and other sources are constantly scavenged by endogenous enzymes (superoxide dismutase, catalase, glutathione peroxidase, etc.) and antioxidants (vitamin E, glutathione, vitamin C, etc.). However, pathologic insults such as ischemia and injury cause perturbation of this defense mechanism and the over-production of oxygen radicals and lipid peroxidation [4, 12, 13, 20]. Moreover, the release of free polyunsaturated fatty acids (PUFAs) from phospholipids of damaged membranes also contributes to the formation of oxygen radicals. The conversion of PGG₂ to PGH₂, HPETE to HETE, and HPETE to leukotriene A₄ (LTA₄) will produce the active oxygen radical species [21, 23]. The pathologic role of these oxygen radicals in CNS injury is not clear. Using cortical brain slices as an in vitro bioassay system, we have demonstrated that oxygen radicals produced by an exogenous xanthine oxidase system induce lipid peroxidation and the development of cellular (cytotoxic) edema [6].

The work described in this paper was supported by the NIH Brain Edema Research Center (grant no. 2 POI-14 543–07).