The role of reactive oxygen species in animal models of glomerular disease.

Abstract

Reactive oxygen metabolites have been demonstrated to play a pathobiologic role in a number of experimental models of both immune and nonimmune glomerular injury. Using scavenging substances, enzyme inhibitors, and transition metal chelators, all of the major reactive oxygen metabolites have been implicated in glomerular injury. In addition, in neutrophil-dependent models, interaction between neutrophil-derived myeloperoxidase and halide anions has been shown to be involved in glomerular damage, as well as halogenation of the glomerular basement membrane (GBM). Finally, recent attention has focused on the role of cytokines (perhaps elaborated by infiltrating monocytes/macrophages) in stimulating mesangial cells (MC) to produce reactive oxygen species. Theoretically, this pathobiologic sequence could further enhance an inflammatory state within the glomerular tuft and enable the propagation of initial glomerular injury, which may be associated with an increase in monocyte infiltration into the mesangium, to glomerulosclerosis in experimental models that manifest this transition.