Effects of probucol on renal function in rats with bilateral ureteral obstruction.
To ascertain the potential role of reactive oxygen metabolites in the pathophysiology of obstructive uropathy, we examined the effect of probucol, an antioxidant agent, on renal function in normal rats and rats with unilateral release of bilateral ureteral obstruction (BUO) of 24 hours duration. Rats were fed either a standard diet or a standard diet containing one percent probucol for two weeks prior to study. Probucol lowered serum cholesterol in both normal and BUO rats. Probucol did not significantly affect renal function in normal rats. BUO rats given probucol had greater inulin and PAH clearances at three to five hours and three days following release of BUO than rats with BUO not given probucol. Kidneys from obstructed rats had higher levels of malondialdehyde, an index of lipid peroxidation, a greater number of leukocytes in the cortex, decreased levels of reduced glutathione and increased levels of oxidized glutathione. Renal cortex from obstructed rats treated with probucol had significantly higher levels of reduced glutathione than kidneys of obstructed rats not given probucol. A decrease in cholesterol, using another lipid-lowering agent, lovastatin, did not modify renal function in rats with BUO. The data can be interpreted to indicate a role for reactive oxygen species in the pathophysiology of obstructive nephropathy. The improved renal function seen in probucol-treated rats with BUO may be due to an effect of this agent in affecting accumulation of reactive oxygen metabolites and/or decreasing the number of leukocytes infiltrating the renal cortex.
Modi
K S
KS
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Morrissey
J
J
Shah
S V
SV
Schreiner
G F
GF
Klahr
S
S
D000818:Animals; D005260:Female; D016166:Free Radical Scavengers; D005609:Free Radicals; D005978:Glutathione / Q000032:analysis; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000032:analysis; D011292:Premedication; D011341:Probucol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014517:Ureteral Obstruction / Q000503:physiopathology*
D016166:Free Radical Scavengers; D005609:Free Radicals; D008315:Malondialdehyde; D005978:Glutathione; D011341:Probucol