The role of reactive oxygen metabolites in glomerular disease.

Abstract

A large body of evidence accumulated over the last decade indicates that partially reduced oxygen metabolites are important mediators of ischemic, toxic, and immune-mediated tissue injury (7, 19, 30, 32, 52, 82). Numerous studies have examined the role of reactive oxygen metabolites in leukocyte­ dependent and -independent models and the biological effects these metabo­ lites have in glomerular pathophysiology (9, 21, 73, 74). In this review, I define the term reactive oxygen metabolites, briefly recount the sequence of events that led to the consideration of these metabolites as important mediators of tissue injury, and present the available evidence in support of the role of reactive oxygen metabolites in glomerular disease, including the recent studies in which the role of intrinsic antioxidant defenses are beginning to be deline­ ated. Oxygen normally accepts four electrons and is converted directly to water. However, partial reduction of oxygen can and does occur in biological systems, which leads to the generation of partially reduced and potentially toxic reactive oxygen intermediates (33, 53). Thus sequential reduction of oxygen along the univalent pathway leads to the generation of superoxide anion, hydrogen peroxide, hydroxyl radical, and water (33, 53).