Faculty Collaboration Database

Superoxide dismutase mimetic preserves the glomerular capillary permeability barrier to protein. J Pharmacol Exp Ther 2006 Mar;316(3):1249-54

Date

11/24/2005

Pubmed ID

16303918

DOI

10.1124/jpet.105.092957

Scopus ID

2-s2.0-33644784926 (requires institutional sign-in at Scopus site)   27 Citations

Abstract

Overproduction of superoxide (O2*) occurs in glomerular disease and may overwhelm the capacity of superoxide dismutase (SOD), thereby intensifying oxidant injury by O2* 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-alpha (TNFalpha). 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 TNFalpha has been shown to mediate albuminuria. To increase glomerular capillary permeability to albumin (P(alb)) ex vivo, isolated glomeruli were incubated with TNFalpha at concentrations (0.5-4.0 microg/ml) known to stimulate O2* production. Increments in P(alb) were detected by measuring changes in glomerular volume in response to an applied oncotic gradient. Significant increases in the urine excretion of albumin and F(2alpha)-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, TNFalpha increased P(alb) 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 O2* production.

Author List

Duann P, Datta PK, Pan C, Blumberg JB, Sharma M, Lianos EA

Author

Cynthia G. Pan MD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antibodies
Autoantibodies
Capillary Permeability
Cyclic N-Oxides
Kidney Glomerulus
Proteins
Proteinuria
Rats
Rats, Inbred Lew
Spin Labels
Superoxides
Tumor Necrosis Factor-alpha