Effects of probucol in renal function and structure in rats with subtotal kidney ablation.
Probucol is a bisphenolic compound that lowers serum cholesterol and also has potent antioxidant properties. The present studies examined the effects of probucol administration on renal function and structure in a rat model of subtotal renal ablation. After subtotal nephrectomy, rats were fed an isocaloric rat chow diet containing 22.8% protein with or without the addition of 1% probucol. After 4 weeks, clearance studies were performed for determination of glomerular filtration rate (inulin clearance) and effective renal plasma flow (paraaminohippurate clearance). After completion of clearance studies and measurements of arterial blood pressure, the animals were exsanguinated and renal tissue was obtained for histologic evaluation. There were no differences in body weight, hematocrit, and blood pressure between the two groups of rats 4 weeks after subtotal nephrectomy. Rats with a remnant kidney given probucol had a significantly lower serum cholesterol level (47.4 +/- 5.3 mg/dl vs 87.2 +/- 10.4 mg/dl) and urea nitrogen level (40.7 +/- 3.2 mg/dl vs 63.6 +/- 8.1 mg/dl) than the control group. Rats given probucol also had significantly greater values for inulin clearance and clearance of paraaminohippurate and significantly less proteinuria than control rats. Also, rats with a remnant kidney given probucol had a significantly greater number of normal glomeruli (6.2% +/- 2.1% vs 1.1% +/- 0.9%) and a lesser number of severely affected glomeruli, grades III and IV (26.0% +/- 5.9% vs 50.9% +/- 9.1%) than rats with a remnant kidney not given probucol. Tubulointerstitial changes also were significantly less in rats with a remnant kidney given probucol.(ABSTRACT TRUNCATED AT 250 WORDS)
Modi
K S
KS
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Schreiner
G F
GF
Purkerson
M L
ML
Klahr
S
S
D000818:Animals; D001284:Atrophy; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D005260:Female; D005355:Fibrosis; D006400:Hematocrit; D007668:Kidney / Q000187:drug effects / Q000473:pathology* / Q000502:physiology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D011341:Probucol / Q000494:pharmacology* / Q000633:toxicity; D011507:Proteinuria; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D014508:Urea / Q000378:metabolism
D012709:Serum Albumin; D014280:Triglycerides; D014508:Urea; D002784:Cholesterol; D011341:Probucol