Blockade of oxidative stress by vitamin C ameliorates albuminuria and renal sclerosis in experimental diabetic rats.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Lee
Eun Young
EY
Department of Internal Medicine, Yonsei University Wonju College of Medicine, 162 Ilsan-dong, Wonju 220-701, Korea.
Lee
Mi Young
MY
Hong
Soon Won
SW
Chung
Choon Hee
CH
Hong
Sae Yong
SY
D000419:Albuminuria / Q000188:drug therapy*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000473:pathology; D007668:Kidney / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D020334:Rats, Inbred OLETF; D012598:Sclerosis
D000975:Antioxidants; D001205:Ascorbic Acid