Hydroxyl radical scavengers ameliorate proteinuria in rat immune complex glomerulonephritis.
We examined the effect of the administration of different oxygen radical scavengers on the development of glomerulonephritis induced by cationic bovine gamma-globulin (cBGG). Treatment with the H2O2 scavenger catalase or the superoxide anion (O2-) scavenger superoxide dismutase (SOD) did not significantly reduce proteinuria. In contrast, treatment with the hydroxyl radical (OH.) scavengers dimethyl sulfoxide (DMSO) or dimethylthiourea resulted in significant decrements in proteinuria, from 156 +/- 20 mg/24 hours in saline solution--treated control rats to 70 +/- 17 mg/24 hours (p less than 0.05) and 37 +/- 10 mg/24 hours (p less than 0.01) in DMSO- and dimethylthiourea-treated rats, respectively. Therapy with DMSO for 5 days after induction of glomerular disease also resulted in amelioration of proteinuria, 10.0 +/- 5.0 mg/24 hours versus saline solution-treated rats, 67.6 +/- 16.2 mg/24 hours (p less than 0.005). OH. scavenger therapy did not influence glomerular morphology, glomerular immunoglobulin G (IgG), or complement deposition, or creatinine clearances of rats with glomerulonephritis. Furthermore, there were no significant differences in serum levels of C3 and C5 or anti-BGG antibody production between DMSO-treated rats and control rats. None of the radical scavengers administered altered the enhanced glomerular thromboxane synthesis characteristic of this model. Our results suggest that OH. generation mediates in part glomerular injury in cBGG-induced glomerulonephritis.
Rahman
M A
MA
Department of Medicine, Case Western Reserve University, Cleveland, Ohio.
Emancipator
S S
SS
Sedor
J R
JR
D000818:Animals; D003176:Complement C3 / Q000032:analysis; D003182:Complement C5 / Q000032:analysis; D003404:Creatinine / Q000493:pharmacokinetics; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005921:Glomerulonephritis / Q000378:metabolism*; D006878:Hydroxides; D017665:Hydroxyl Radical; D007105:Immune Complex Diseases / Q000378:metabolism*; D007074:Immunoglobulin G / Q000032:analysis; D007678:Kidney Glomerulus / Q000473:pathology; D011453:Prostaglandins / Q000096:biosynthesis; D011507:Proteinuria / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology; D005719:gamma-Globulins / Q000276:immunology
D003176:Complement C3; D003182:Complement C5; D006878:Hydroxides; D007074:Immunoglobulin G; D011453:Prostaglandins; D005719:gamma-Globulins; D017665:Hydroxyl Radical; D003404:Creatinine; D013482:Superoxide Dismutase; D004121:Dimethyl Sulfoxide