Yonsei Med J.  2007 Oct;48(5):847-855. 10.3349/ymj.2007.48.5.847.

Blockade of Oxidative Stress by Vitamin C Ameliorates Albuminuria and Renal Sclerosis in Experimental Diabetic Rats

• Lee EY
• Lee MY
• Hong SW
• Chung CH
• Hong SY

• KMID: 1122624
• DOI: http://doi.org/10.3349/ymj.2007.48.5.847

Abstract

PURPOSE: Oxidative stress has been suggested to play a role as a common mediator of apoptosis and kidney damage in diabetes. However, it is uncertain whether the apoptosis occurs in the kidney during the course of diabetes. We investigated the occurrence of apoptosis in the diabetic rat kidney, the role of oxidative stress and the effect of an antioxidant on apoptosis in the diabetic rat kidney. MATERIALS AND METHODS: Otsuka-Long-Evans-Tokushima-Fatty rats, an animal model for type 2 diabetes, were randomized into a non-treated diabetic (n=8) and a vitamin C-treated group (n=8). Long-Evans Tokushima Otsuka rats (n=8) were used as a control. RESULTS: Apoptosis was present in the epithelial cells of the proximal tubules in diabetic rats. The number of apoptotic cells, albuminuria, proteinuria, glomerular and tubulointerstitial sclerosis, and renal malondialdehyde were significantly decreased in vitamin C-treated diabetic rats when compared to the untreated diabetic rats. The decreased slit pore density (number of slit pores per underlying glomerular basement membrane length) as assessed by electron microscopy was also significantly restored by treatment with vitamin C without significantly affecting plasma glucose in diabetic rats. CONCLUSION: By blocking these pathophysiologic processes, a blockade of oxidative stress by vitamin C might become a useful adjunct to albuminuria and renal sclerosis in diabetic nephropathy.

Keyword

Apoptosis; diabetic nephropathy; oxidative stress; slit pore; vitamin C

MeSH Terms

Albuminuria/*drug therapy
Animals
Antioxidants/*therapeutic use
Apoptosis/drug effects
Ascorbic Acid/*therapeutic use
Diabetes Mellitus, Experimental/*drug therapy/pathology
Diabetic Nephropathies/*drug therapy/pathology
Kidney/*pathology
Male
Oxidative Stress/*drug effects
Rats
Rats, Inbred OLETF
Sclerosis

Figure

• 

  Fig. 1 Effects of vitamin C on urinary protein and albumin excretion in diabetic rats. Values are means ± SD. D, diabetic rats; D + VC, diabetic rats treated with vitamin C; C, non-diabetic control rats. *p < 0.001 compared with C, †p < 0.001 compared with D, ††p < 0.05 compared with D.

• 

  Fig. 2 Effect of vitamin C on renal MDA in diabetic rats. Values are means ± SD. Values are means ± SD. D, diabetic rats; D + VC, diabetic rats treated with vitamin C; C, non-diabetic control rats. *p < 0.001 compared with C, †p < 0.001 compared with D.

• 

  Fig. 3 Effect of vitamin C on slit pore density in diabetic rats. The slit pore density was expressed as the number of slit pores between podocyte foot processes per millimeter length of glomerular basement membrane by electron microscopy. Representative electron photomicrographs show examples of slit pores (arrows), which are more prevalent in the diabetic rats. D, diabetic rats (A); D + VC, diabetic rats treated with vitamin C (B); C, non-diabetic control rats(C). Magnification, × 40,000. **p < 0.05 compared with C, ††p < 0.01 compared with D.

• 

  Fig. 4 Apoptosis in diabetic glomeruli. Intranucleosomal DNA fragmentation was labeled using the In Situ Cell Death Detection Kit after 16 weeks of vitamin C treatment, as described in Materials and Methods. D, diabetic rats (A); C, non-diabetic control rats (B). Magnification, × 400.

• 

  Fig. 5 Effects of vitamin C on apoptosis in diabetic rats. Intranucleosomal DNA fragmentation was labeled using the Apoptosis detection system after 16 weeks of vitamin C treatment, as described in Materials and Methods. D, diabetic rats (A); D + VC, diabetic rats treated with vitamin C (B). Magnification, × 100. Apoptosis positive cells were counted in sixconsecutive interstitial fields under the microscope and expressed as the mean numbers of positive cells of the interstitial field (C). Values are means ± SD. D, diabetic rats; D + VC, diabetic rats treated with vitamin C. *p < 0.05 compared with D.

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