TY - JOUR T1 - Superoxide Dismutase Mimetic Preserves the Glomerular Capillary Permeability Barrier to Protein JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1249 LP - 1254 DO - 10.1124/jpet.105.092957 VL - 316 IS - 3 AU - Pu Duann AU - Prasun K. Datta AU - Cynthia Pan AU - Jeffrey B. Blumberg AU - Mukut Sharma AU - Elias A. Lianos Y1 - 2006/03/01 UR - http://jpet.aspetjournals.org/content/316/3/1249.abstract N2 - Overproduction of superoxide () occurs in glomerular disease and may overwhelm the capacity of superoxide dismutase (SOD), thereby intensifying oxidant injury by and related radical species that disrupt the glomerular capillary permeability barrier to protein. We examined the efficacy of the SOD mimetic tempol in preserving glomerular permeability to protein using 1) a rat model of glomerular immune injury induced by an antiglomerular basement membrane antibody (anti-GBM), and 2) isolated rat glomeruli in which injury was induced by the cytokine tumor necrosis factor-α (TNFα). To induce glomerular immune injury, rats received anti-GBM using a protocol that results in prominent infiltration of glomeruli by macrophages and in which macrophage-derived TNFα has been shown to mediate albuminuria. To increase glomerular capillary permeability to albumin (Palb) ex vivo, isolated glomeruli were incubated with TNFα at concentrations (0.5–4.0 μg/ml) known to stimulate production. Increments in Palb were detected by measuring changes in glomerular volume in response to an applied oncotic gradient. Significant increases in the urine excretion of albumin and F2α-isoprostane were observed in rats with glomerular immune injury without a significant change in systolic blood pressure. Tempol treatment significantly reduced urine isoprostane and albumin excretion. In isolated glomeruli, TNFα increased Palb and tempol abrogated this effect, both in a dose-dependent manner. These observations indicate that SOD mimetics can preserve the glomerular permeability barrier to protein under conditions of oxidative stress from production. ER -