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Published on: June 23, 2015
Effect of probucol in a murine model of slowly progressive polycystic kidney disease
S Nagao1, T Yamaguchi, M Kasahara
1Institute for Comprehensive Medical Science and the Department of Pathology, School of Medicine, Fujita Health University, Toyoake, Japan.
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.
Insights
Probucol, an antioxidant, significantly reduced kidney size, cyst expansion, fibrosis, and improved renal function in a mouse model of polycystic kidney disease. This suggests probucol may be a potential therapeutic agent for this condition.
Area of Science:
- Nephrology
- Pharmacology
- Biochemistry
Background:
- Polycystic kidney disorders involve epithelial proliferation, extracellular matrix remodeling, and inflammation.
- Probucol is an antioxidant with cholesterol-lowering properties, previously shown to benefit vascular conditions.
Purpose of the Study:
- To investigate the effects of probucol on the progression of kidney disease in a mouse model.
- To evaluate probucol's impact on kidney structure and function under a high-protein diet.
Main Methods:
- Male BDF1-pcy hybrid mice were fed a 1% probucol diet for 200 days.
- A high-protein diet (36%) was used to exacerbate kidney disease.
- Kidney weight, cyst expansion, fibrosis, and serum urea nitrogen were assessed.
Main Results:
- Probucol reduced serum cholesterol but did not affect food intake or body weight.
- Significant decreases were observed in relative kidney weight (KW/BW), serum urea nitrogen (SUN), cystic index, and fibrosis index.
- Probucol treatment ameliorated structural and functional kidney deterioration.
Conclusions:
- Probucol demonstrates protective effects against the progression of polycystic kidney disease in mice.
- The findings suggest probucol may be a viable therapeutic option for managing kidney disease, particularly when combined with high dietary protein.
