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

Shizuko Nagao, Tamio Yamaguchi, Masao Kasahara, Masatomo Kusaka, Jun Matsuda, Noboru Ogiso, Hisahide Takahashi, Jared J. Grantham

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)221-226
Number of pages6
JournalAmerican Journal of Kidney Diseases
Volume35
Issue number2
DOIs
Publication statusPublished - 01-01-2000

Fingerprint

Probucol
Polycystic Kidney Diseases
Kidney
Fibrosis
Body Weight
Urea
Cysts
Nitrogen
Serum
Cholesterol
Coronary Restenosis
Diet
Weights and Measures
Dietary Proteins
Angioplasty
Smooth Muscle Myocytes
Extracellular Matrix
Blood Vessels
Eating
Antioxidants

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Nagao, Shizuko ; Yamaguchi, Tamio ; Kasahara, Masao ; Kusaka, Masatomo ; Matsuda, Jun ; Ogiso, Noboru ; Takahashi, Hisahide ; Grantham, Jared J. / Effect of probucol in a murine model of slowly progressive polycystic kidney disease. In: American Journal of Kidney Diseases. 2000 ; Vol. 35, No. 2. pp. 221-226.
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abstract = "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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Nagao, S, Yamaguchi, T, Kasahara, M, Kusaka, M, Matsuda, J, Ogiso, N, Takahashi, H & Grantham, JJ 2000, 'Effect of probucol in a murine model of slowly progressive polycystic kidney disease', American Journal of Kidney Diseases, vol. 35, no. 2, pp. 221-226. https://doi.org/10.1016/S0272-6386(00)70330-1

Effect of probucol in a murine model of slowly progressive polycystic kidney disease. / Nagao, Shizuko; Yamaguchi, Tamio; Kasahara, Masao; Kusaka, Masatomo; Matsuda, Jun; Ogiso, Noboru; Takahashi, Hisahide; Grantham, Jared J.

In: American Journal of Kidney Diseases, Vol. 35, No. 2, 01.01.2000, p. 221-226.

Research output: Contribution to journalArticle

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AU - Nagao, Shizuko

AU - Yamaguchi, Tamio

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AU - Kusaka, Masatomo

AU - Matsuda, Jun

AU - Ogiso, Noboru

AU - Takahashi, Hisahide

AU - Grantham, Jared J.

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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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