TY - JOUR
T1 - Effect of probucol in a murine model of slowly progressive polycystic kidney disease
AU - Nagao, Shizuko
AU - Yamaguchi, Tamio
AU - Kasahara, Masao
AU - Kusaka, Masatomo
AU - Matsuda, Jun
AU - Ogiso, Noboru
AU - Takahashi, Hisahide
AU - Grantham, Jared J.
N1 - Funding Information:
Supported in part by grants-in-aid from the Ministry of Education, Science and Culture of Japan, from the scientific research funds from Fujita Health University, and NIH P01 DK53763.
PY - 2000
Y1 - 2000
N2 - Epithelial proliferation, extracellular matrix remodeling, and interstitial inflammation are central elements in the pathogenesis of slowly progressive polycystic kidney disorders. Probucol, an antioxidant that lowers plasma cholesterol, has been shown to decrease smooth muscle cell proliferation and 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 body weight (KW/BW), cyst expansion, renal interstitial fibrosis, and serum urea nitrogen (SUN) concentration. Animals were fed a moderately high-protein diet (HPD, 36%) to accentuate the development of renal cysts and to promote interstitial fibrosis. Probucol decreased serum cholesterol from 68 to 16 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 from 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 ameliorates the progressive deterioration in renal function and structure in pcy mice ingesting a relatively high level of dietary protein. (C) 2000 National Kidney Foundation, Inc.
AB - Epithelial proliferation, extracellular matrix remodeling, and interstitial inflammation are central elements in the pathogenesis of slowly progressive polycystic kidney disorders. Probucol, an antioxidant that lowers plasma cholesterol, has been shown to decrease smooth muscle cell proliferation and 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 body weight (KW/BW), cyst expansion, renal interstitial fibrosis, and serum urea nitrogen (SUN) concentration. Animals were fed a moderately high-protein diet (HPD, 36%) to accentuate the development of renal cysts and to promote interstitial fibrosis. Probucol decreased serum cholesterol from 68 to 16 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 from 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 ameliorates the progressive deterioration in renal function and structure in pcy mice ingesting a relatively high level of dietary protein. (C) 2000 National Kidney Foundation, Inc.
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U2 - 10.1016/S0272-6386(00)70330-1
DO - 10.1016/S0272-6386(00)70330-1
M3 - Article
C2 - 10676720
AN - SCOPUS:0033978463
SN - 0272-6386
VL - 35
SP - 221
EP - 226
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 2
ER -