Poly(ADP-Ribose)Polymerase Inhibition Counteracts Cataract Formation and Early Retinal Changes in Streptozotocin-Diabetic Rats

2009 ◽  
Vol 50 (4) ◽  
pp. 1778 ◽  
Author(s):  
Viktor R. Drel ◽  
Weizheng Xu ◽  
Jie Zhang ◽  
Peter F. Kador ◽  
Tayyeba K. Ali ◽  
...  
2000 ◽  
Vol 84 (4) ◽  
pp. 575-582 ◽  
Author(s):  
Rhonda C. Bell ◽  
John C. Carlson ◽  
Katrina C. Storr ◽  
Kelley Herbert ◽  
Jacob Sivak

We examined the effects of high-fructose (FR) feeding on the development of diabetic complications in the lens and the kidney of streptozotocin (STZ)-diabetic rats. Male Wistar Furth rats were treated with one of two doses of STZ (HIGH STZ, 55 mg/kg body weight; MOD STZ, 35 mg/kg body weight) or vehicle alone (SHAM) and were then assigned to a control (CNTL) or 400 g FR/kg diet for 12 weeks. At the end of the study, body weight, plasma glucose and insulin concentrations differed among STZ groups (HIGH v. MOD v. SHAM, P<0·001) but did not differ due to diet. Plasma FR concentrations were significantly higher in FR-fed v. CNTL-fed groups (P<0·0001) and in HIGH-STZ groups v. MOD-STZ and SHAM groups (P<0·0004 and P<0·0001 respectively). Focal length variability of the lens, a quantitative measure of cataract formation, was increased in the HIGH STZ, FR group compared with the HIGH STZ, CNTL group (P<0·01). The concentration of H2O2 in kidney microsomes was significantly higher in HIGH STZ, FR rats v. HIGH STZ, CNTL rats (P<0·01). Microalbuminuria was not observed in any of the groups examined, and there was no evidence of extensive histological damage in the kidney from any rats. Under conditions of severe hyperglycaemia, high FR intake promotes the development of cataracts in the lens of the eye, and results in increased concentrations of substances indicative of oxidative stress in the kidney. Although FR has been suggested as a carbohydrate source for diabetics, a high FR diet coupled with hyperglycaemia produces effects that may promote some of the complications associated with diabetes.


1991 ◽  
Vol 266 (14) ◽  
pp. 8671-8674
Author(s):  
E. Unger ◽  
I. Pettersson ◽  
U.J. Eriksson ◽  
U. Lindahl ◽  
L. Kjellén

2002 ◽  
Vol 3 (2) ◽  
pp. 119-130 ◽  
Author(s):  
Fulya Zobali ◽  
Tanju Besler ◽  
Nuray Ari ◽  
Çimen Karasu

A positive correlation has been established between increased oxidative stress and cardiovascular diseases in diabetes mellitus. We evaluated the effects of single or combined treatments with vitamin A (retinol acetate, 30 mg/kg/day, for 12-weeks) and insulin (8-10 IU/rat/day for the final 6-week) on vasomotor activity, oxidative stress and retinol metabolism in 12-week streptozotocin diabetic rats. The vasomotor activity was determined by measuring invitroresponsiveness of aorta rings to phenylephrine (PE) and acetylcholine (ACh) in the absence or in the presence of hydrogen peroxide (H2O2). Preincubation withH2O2(10 μM) produced a significant decrease in PE (1 mM)-induced contraction in untreated-diabetic but not in control rats. Single treatment with insulin counteracted this effect ofH2O2and also reversed the increased contractile response of diabetic aorta to PE, while vitamin A was found to be ineffective.H2O2(10 μM) also inhibited ACh (1 mM)-stimulated endothelium- dependent relaxation two fold more in diabetic than in control aorta. In the prevention ofH2O2-induced inhibition of vascular relaxation to ACh, vitamin A alone was markedly effective while insulin alone was not. The combination of vitamin A plus insulin removed the inhibitory action ofH2O2in diabetic aorta. Diabetic animals displayed an increased level of aorta thiobarbituric acid reactive substance (TBARS) in association with decreased levels of plasma retinol and retinol-binding protein (RBP). Single treatment with insulin, in spite of allowing recovery of normal growth rate and improved glucose and retinol metabolism in diabetic rats, was unable to control TBARS production to the same extent as vitamin A alone. Our findings suggest that the maintenance of ACh-stimulated endothelium-dependent vasorelaxant tone in normal physiological levels depends largely on the prevention and/or inhibition of peroxidative stress, which is achieved by combined treatment with vitamin A plus insulin. The use of vitamin A together with insulin provides a better metabolic control and more benefits than use of insulin alone in the reduction of diabetes-induced vascular complications.


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