Effect of probucol in a murine model of slowly progressive polycystic kidney disease

Epithelial proliferation, extracellular matrix remodeling, and interstitial inflammation are central elements in the pathogenesis of slowly progressiv e polycystic kidney disorders. Probucol, an antioxidant that lowers plasma cholesterol, has been shown to decrease smooth muscle cell proliferation an d macrophage accumulation in blood vessels and to prevent restenosis after coronary angioplasty, We determined in 30-day-old male BDF1-pcy hybrid mice (derived from mating DBA/2FG-pcy and C57BL/6FG-pcy) the effect of probucol administered in the diet (1%) for 200 days on kidney weight relative to bo dy weight (KW/BW), cyst expansion, renal interstitial fibrosis, and serum u rea nitrogen (SUN) concentration. Animals were fed a moderately high-protei n diet (HPD, 36%) to accentuate the development of renal cysts and to promo te interstitial fibrosis. Probucol decreased serum cholesterol from 68 to 1 6 mg/dL but had no effect on food intake or body weight. Probucol decreased relative kidney size from 4.16% +/- 0.55% to 2.64% +/- 0.12% KW/BW (P < 0. 01), SUN from 30.5 +/- 1.8 to 25.9 +/- 1.0 mg/dL (P < 0.05), cystic index f rom 2.45 +/- 0.11 to 1.36 +/- 0.10 (P < 0.01), and fibrosis index from 2.40 +/- 0.11 to 1.82 +/- 0.08 (P < 0.01). We conclude that probucol ameliorate s the progressive deterioration in renal function and structure in pcy mice ingesting a relatively high level of dietary protein. (C) 2000 by the Nati onal Kidney Foundation, Inc.